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Elliott J, Tang PK. Fibroblast growth factor 23 - A review with particular reference to the physiology and pathophysiology of phosphate homeostasis in the cat. Vet J 2025; 309:106271. [PMID: 39608700 DOI: 10.1016/j.tvjl.2024.106271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 09/08/2024] [Accepted: 11/24/2024] [Indexed: 11/30/2024]
Abstract
Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone, discovery of which has transformed our understanding of mineral regulation in healthy mammals, including the cat. It is produced by osteoblasts and osteocytes and its prime role is to regulate phosphate entry into extracellular fluid (from bone and via the gut) and its excretion via the kidney. It interacts with other hormones (calcitriol and parathyroid hormone), inhibiting their activation and secretion respectively and so impacts on calcium as well as phosphate homeostasis. Physiological factors regulating its secretion are not well understood, although phosphate ion sensing is likely to be important. Calcium and magnesium ions are also involved and unravelling the control points and integration of the system regulating bone turnover and mineral balance whilst preventing soft tissue (non-osseous) mineralisation is a future research goal. Calciprotein particle size and number likely play an important role in this system but precisely how remains to be determined. Elevated serum FGF23 is the earliest indicator of mineral bone disorder associated with chronic kidney disease in human patients and in cats, enabling reference-range serum phosphorus to be maintained despite reduction in glomerular filtration rate which limits phosphate excretion. FGF23 also predicts CKD progression and survival in cats. The many factors influencing its secretion at different stages of CKD, including relative iron deficiency, anaemia and chronic systemic inflammation, hypomagnesaemia and α-klotho deficiency are discussed in this review, where the data available in cats with naturally occurring CKD is presented alongside that from rodent models and human CKD patients.
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Affiliation(s)
- Jonathan Elliott
- Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, United Kingdom.
| | - Pak Kan Tang
- Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, United Kingdom
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Koh HB, Kim HJ, Heo GY, Kim HW, Jung CY, Han SH, Yoo TH, Kang SW, Park JT. Association between dietary magnesium intake and incident chronic kidney disease: a prospective observational cohort study. Am J Clin Nutr 2024; 120:964-972. [PMID: 39163977 DOI: 10.1016/j.ajcnut.2024.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 08/08/2024] [Accepted: 08/13/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND Although serum magnesium deficiency is linked to higher cardiovascular disease risk, its association with chronic kidney disease (CKD) remains unclear. OBJECTIVES This study aimed to evaluate the relationship between dietary magnesium intake and CKD development in adults with clinically normal kidney function. METHODS The prospective observational cohort study evaluated 188,510 participants (median age, 57.0 y; female, 54.1%) from the UK Biobank. Dietary magnesium intake was assessed through a 24-h dietary recall questionnaire compromising a list of 206 foods and 32 beverages and categorized into quintiles. The primary outcome was incident CKD diagnosed through International Classification of Diseases-10 and Office of Population Censuses and Surveys 4 codes. Incident CKD, defined as estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, was also assessed in a subcohort with creatinine follow-up data. RESULTS The median magnesium intake amount per person was 323.2 mg/d [interquartile range (IQR): 269.4-382.7 mg/d]. During 1,826,038.1 person-years of follow-up (median: 9.6 y; IQR: 9.3-10.3 y), CKD developed in 5,878 participants. The incidence of CKD was progressively higher in participants with lower magnesium intake (2.8%, 2.8%, 3.0%, 3.2%, and 3.7% in Q5-Q1, respectively). Cox regression analysis revealed that the hazard ratios (HRs) for incident CKD increased in a stepwise manner toward lower magnesium intake quintiles {adjusted HR (95% confidence interval [CI])-Q4: 0.97 (0.89, 1.06); Q3: 1.05 (0.96, 1.14); Q2: 1.12 (1.03, 1.21); Q1: 1.30 (1.20, 1.41)} relative to Q5 (P-linearity < 0.001). Similar results were observed with eGFR-defined CKD outcome [adjusted HR (95% CI)-Q4: 1.09 (0.92, 1.28); Q3: 1.15 (0.98, 1.35); Q2: 1.21 (1.03, 1.42); Q1: 1.41 (1.20, 1.65) relative to Q5; P-linearity < 0.001]. CONCLUSIONS Lower dietary magnesium intake was associated with higher risk of incident CKD in adults with clinically normal kidney function. Further controlled studies are required to establish the potential benefit of adequate magnesium intake.
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Affiliation(s)
- Hee Byung Koh
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea; Catholic Kwandong University International Saint Mary's Hospital, Seo-gu, Incheon, South Korea
| | - Hyo Jeong Kim
- Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ga Young Heo
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea
| | - Hyung Woo Kim
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea
| | - Chan-Young Jung
- Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea
| | - Seung Hyeok Han
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea
| | - Tae-Hyun Yoo
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea
| | - Shin-Wook Kang
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea
| | - Jung Tak Park
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea.
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Perazella MA. Proton Pump Inhibitors and Kidney Disease: What Gives? KIDNEY360 2024; 5:1374-1376. [PMID: 39325592 PMCID: PMC11441802 DOI: 10.34067/kid.0000000000000521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/28/2024]
Affiliation(s)
- Mark A Perazella
- Section of Nephrology, Yale School of Medicine, New Haven, Connecticut
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Nogueira de Sa P, Narayanan M, Lim MAC. Electrolyte and Acid-Base Abnormalities After Kidney Transplantation. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:450-457. [PMID: 39232615 DOI: 10.1053/j.akdh.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 03/14/2024] [Accepted: 03/25/2024] [Indexed: 09/06/2024]
Abstract
Kidney transplantation is the optimal therapeutic approach for individuals with end-stage kidney disease. The Scientific Registry of Transplant Recipients has reported a continuous rise in the total number of kidney transplants performed in the United States, with 25,500 new kidney recipients in 2022 alone. Despite an improved glomerular filtration rate, the post-transplant period introduces a unique set of electrolyte abnormalities that differ from those encountered in chronic kidney disease. A variety of factors contribute to the high prevalence of hypomagnesemia, hyperkalemia, metabolic acidosis, hypercalcemia, and hypophosphatemia seen after kidney transplantation. These include the degree of allograft function, immunosuppressive medications and their diverse mechanisms of action, and metabolic changes after transplant. This article aims to provide a comprehensive review of the key aspects surrounding the most commonly encountered electrolyte and acid-base abnormalities in the post-transplant setting.
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Affiliation(s)
- Patricia Nogueira de Sa
- Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
| | - Mohanram Narayanan
- Division of Nephrology and Hypertension, Department of Medicine, Baylor Scott & White, Medical Center, Temple, TX
| | - Mary Ann C Lim
- Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA
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Kishi S, Nakashima T, Goto T, Nagasu H, Brooks CR, Okada H, Tamura K, Nakano T, Narita I, Maruyama S, Yano Y, Yokoo T, Wada T, Wada J, Nangaku M, Kashihara N. Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease. Clin Exp Nephrol 2024; 28:784-792. [PMID: 38506982 DOI: 10.1007/s10157-024-02486-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 03/05/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. METHODS This is an analysis of the Japan Chronic Kidney Disease Database Ex (J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. RESULTS The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. CONCLUSION Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.
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Affiliation(s)
- Seiji Kishi
- Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, 7010192, Japan.
| | - Takaya Nakashima
- TXP Medical Co. Ltd, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan
| | - Tadahiro Goto
- TXP Medical Co. Ltd, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
| | - Hajime Nagasu
- Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, 7010192, Japan
| | - Craig R Brooks
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Hirokazu Okada
- Department of Nephrology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
| | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ichiei Narita
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Shoichi Maruyama
- Department of Nephrology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Yuichiro Yano
- Department of Advanced Epidemiology, NCD Epidemiology Research Center, Shiga University of Medical Science, Shiga, Japan
| | - Takashi Yokoo
- Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Wada
- Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Jun Wada
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Masaomi Nangaku
- Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Naoki Kashihara
- Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, 7010192, Japan
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Panta R, Regmi S. Role of Magnesium, Effects of Hypomagnesemia, and Benefits of Magnesium Supplements in Cardiovascular and Chronic Kidney Diseases. Cureus 2024; 16:e64404. [PMID: 39130977 PMCID: PMC11317063 DOI: 10.7759/cureus.64404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/12/2024] [Indexed: 08/13/2024] Open
Abstract
Cardiovascular diseases (CVDs) account for nearly half of chronic kidney disease (CKD)-related deaths. Hypomagnesemia has been associated with various cardiovascular conditions and predicts a decline in renal function leading to end-stage renal disease (ESRD). The objective of this review is to delve into and discuss the significance of magnesium (Mg) in cardiovascular and renal functions, the clinical consequences of hypomagnesemia on CVD and CKD, and the benefits of Mg supplementation in managing CVD and CKD. This review is the result of an extensive search for pertinent articles in databases like PubMed, Medline, PubMed Central, and Google Scholar. Based on the literature search conducted in this review, we concluded that Mg protects against various CVDs and delays the progression of CKD. Mg can regulate pathways associated with inflammation, oxidative stress, and fibrosis. Therefore, maintaining slightly elevated Mg levels and timely Mg supplementation may benefit patients with CVD and CKD. There is a need for additional prospective randomized controlled trials to fully comprehend the therapeutic effects of Mg on CVD and CKD along with setting individualized target levels for serum Mg in such patients.
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Affiliation(s)
- Raju Panta
- Physiology and Pathology, Burrell College of Osteopathic Medicine, Melbourne, USA
| | - Subash Regmi
- Critical Care Medicine, University of Southern Carolina, Columbia, USA
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Grams ME, Wilson FP. Proton Pump Inhibitors and CKD: The Evidence Builds. J Am Soc Nephrol 2024; 35:833-834. [PMID: 38809613 PMCID: PMC11230710 DOI: 10.1681/asn.0000000000000398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024] Open
Affiliation(s)
- Morgan E Grams
- Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, New York
- Department of Population Health, New York University Grossman School of Medicine, New York, New York
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - F Perry Wilson
- Clinical and Translational Research Accelerator, Yale University, New Haven, Connecticut
- Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
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Jiang X, Li Z, Pan C, Fang H, Xu W, Chen Z, Zhu J, He L, Fang M, Chen C. The role of serum magnesium in the prediction of acute kidney injury after total aortic arch replacement: A prospective observational study. J Med Biochem 2024; 43:574-586. [PMID: 39139155 PMCID: PMC11318877 DOI: 10.5937/jomb0-48779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 03/21/2024] [Indexed: 08/15/2024] Open
Abstract
Background Considerable morbidity and death are associated with acute kidney damage (AKI) following total aortic arch replacement (TAAR). The relationship between AKI following TAAR and serum magnesium levels remains unknown. The intention of this research was to access the predictive value of serum magnesium levels on admission to the Cardiovascular Surgical Intensive Care Unit (CSICU) for AKI in patients receiving TAAR. Methods From May 2018 to January 2020, a prospective, observational study was performed in the Guangdong Provincial People's Hospital CSICU. Patients accepting TAAR admitted to the CSICU were studied. The Kidney Disease: Improving Global Outcomes (KDIGO) definition of serum creatinine was used to define AKI, and KDIGO stages two or three were used to characterize severe AKI. Multivariable logistic regression and area under the curve receiver-operator characteristic curve (AUC-ROC) analysis were conducted to assess the predictive capability of the serum magnesium for AKI detection. Finally, the prediction model for AKI was established and internally validated. Results Of the 396 enrolled patients, AKI occurred in 315 (79.5%) patients, including 154 (38.8%) patients with severe AKI. Serum magnesium levels were independently related to the postoperative AKI and severe AKI (both, P < 0.001), and AUC-ROCs for predicting AKI and severe AKI were 0.707 and 0.695, respectively. Across increasing quartiles of serum magnesium, the multivariable-adjusted odds ratios (95% confidence intervals) of postoperative AKI were 1.00 (reference), 1.04 (0.50-2.82), 1.20 (0.56-2.56), and 6.19 (2.02-23.91) (P for Trend < 0.001). When serum magnesium was included to a baseline model with established risk factors, AUC-ROC (0.833 vs 0.808, P = 0.050), reclassification (P < 0.001), and discrimination (P = 0.002) were further improved. Conclusions Serum magnesium levels on admission are an independent predictor of AKI. In TAAR patients, elevated serum magnesium levels were linked to an increased risk of AKI. In addition, the established risk factor model for AKI can be considerably improved by the addition of serum magnesium in TAAR patients hospitalized in the CSICU.
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Affiliation(s)
- Xinyi Jiang
- South China University of Technology, School of Medicine, Guangzhou, Guangdong Province, China
| | - Ziyun Li
- Guangdong Medical University, Maoming Clinical College, Maoming, Guangdong Province, China
| | - Chixing Pan
- Guangdong Medical University, Maoming Clinical College, Maoming, Guangdong Province, China
| | - Heng Fang
- Southern Medical University, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Department of Critical Care Medicine, Guangzhou, Guangdong Province, China
| | - Wang Xu
- Southern Medical University, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Department of Intensive Care Unit of Cardiac Surgery, Guangzhou, Guangdong Province, China
| | - Zeling Chen
- Southern Medical University, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Department of Intensive Care Unit of Cardiac Surgery, Guangzhou, Guangdong Province, China
| | - Junjiang Zhu
- Southern Medical University, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Department of Intensive Care Unit of Cardiac Surgery, Guangzhou, Guangdong Province, China
| | - Linling He
- Shenzhen People's Hospital, Department of Critical Care Medicine, Shenzhen, Guangdong Province, China
| | - Miaoxian Fang
- Southern Medical University, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Department of Intensive Care Unit of Cardiac Surgery, Guangzhou, Guangdong Province, China
| | - Chunbo Chen
- South China University of Technology, School of Medicine, Guangzhou, Guangdong Province, China
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Suppadungsuk S, Thongprayoon C, Nikravangolsefid N, Singh W, Cheungpasitporn W, Dong Y, Kashani KB. Magnesium Derangement among Critically Ill Patients with Acute Kidney Injury: An Association with Acute Kidney Disease. Nephron Clin Pract 2024; 148:553-562. [PMID: 38861941 DOI: 10.1159/000539674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 05/28/2024] [Indexed: 06/13/2024] Open
Abstract
INTRODUCTION The association between magnesium level and progression to acute kidney disease (AKD) in acute kidney injury (AKI) patients was not well studied. With AKI transition to AKD, the burden of the disease on mortality, morbidity, and healthcare costs increases. Serum magnesium disturbances are linked with a decline in renal function and increased risk of death in CKD and hemodialysis patients. This study aims to assess the significance of magnesium derangements as a risk factor for the progression of AKI to AKD in critically ill patients. METHODS This study was conducted among patients with AKI admitted to the intensive care units at Mayo Clinic from 2007 to 2017. Serum magnesium at AKI onset was categorized into five groups of <1.7, 1.7-1.9, 1.9-2.1, 2.1-2.3, and ≥2.3 mg/dL, with 1.9-2.1 mg/dL as the reference group. AKD was defined as AKI that persisted >7 days following the AKI onset. Logistic regression was used to evaluate the association between magnesium and AKD. RESULTS Among 20,198 critically ill patients with AKI, the mean age was 66 ± 16 years, and 57% were male. The mean serum magnesium at AKI onset was 1.9 ± 0.4 mg/dL. The overall incidence of AKD was 31.4%. The association between serum magnesium and AKD followed a U-shaped pattern. In multivariable analysis, serum magnesium levels were associated with increased risk of AKD with the odds ratio of 1.17 (95% CI: 1.07-1.29), 1.13 (95% CI: 1.01-1.26), and 1.65 (95% CI: 1.48-1.84) when magnesium levels were <1.7, 2.1-2.3, and ≥2.3 mg/dL, respectively. CONCLUSION Among patients with AKI, magnesium level derangement was an independent risk for AKD in critically ill AKI patients. Monitoring serum magnesium and proper correction in critically ill patients with AKI should be considered an AKD preventive intervention in future trials.
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Affiliation(s)
- Supawadee Suppadungsuk
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA,
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand,
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Nasrin Nikravangolsefid
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Waryaam Singh
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Yue Dong
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Kianoush B Kashani
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
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Pluquet M, Kamel S, Alencar de Pinho N, Mansencal N, Combe C, Metzger M, Massy ZA, Liabeuf S, Laville SM. Ionized and total magnesium levels in patients with chronic kidney disease: associated factors and outcomes. Clin Kidney J 2024; 17:sfae046. [PMID: 38572502 PMCID: PMC10986257 DOI: 10.1093/ckj/sfae046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Indexed: 04/05/2024] Open
Abstract
Background The association between hypo- and/or hypermagnesaemia and cardiovascular (CV) outcomes or mortality has shown conflicting results in chronic kidney disease (CKD) and has been conducted on total magnesium (tMg) levels. Thus, the objectives of the present study were to (i) describe the serum ionized Mg (iMg) concentration in patients at various CKD stages, (ii) measure the correlation between iMg and tMg concentrations, (iii) identify their associated factors and (iv) determine whether serum tMg and/or iMg concentrations are associated with major adverse cardiovascular events (MACE) and mortality before kidney replacement therapy in CKD patients. Methods Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort of CKD patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Baseline iMg and tMg serum concentrations were centrally measured. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios (HRs) for first MACE and for mortality. Results Of the 2419 included patients, median age was 68 years, and the mean eGFR was 34.8 mL/min/1.73 m2. Concentrations of serum iMg and tMg were strongly correlated (r = 0.89, P < .001) and were independently associated with eGFR. The adjusted HR [95% confidence interval (CI)] for MACE associated with the baseline serum tMg level was 1.27 (0.95; 1.69) for patients in Tertile 1 and 1.56 (1.18; 2.06) for patients in Tertile 3, relative to patients in Tertile 2. The HR (95% CI) of death according to serum tMg concentration was increased in Tertile 3 [1.48 (1.11; 1.97)]. The adjusted risk for MACE and mortality (all-cause or CV) associated with the baseline serum iMg level was not significantly different between tertiles. Conclusions Our analysis of a large cohort of patients with moderate-to-advanced CKD demonstrated that individuals with higher serum tMg concentrations, although still within the normal range, had a greater likelihood of MACE and mortality. However, serum iMg levels were not associated with these outcomes.
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Affiliation(s)
- Maxime Pluquet
- MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France
| | - Said Kamel
- MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France
- Department of Biochemistry, Amiens-Picardie University Medical Center, Amiens, France
| | - Natalia Alencar de Pinho
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif, France
| | - Nicolas Mansencal
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif, France
- Department of Cardiology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt, Paris, France
| | - Christian Combe
- Service de Néphrologie Transplantation Dialyse Aphérèse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
- INSERM, U1026, Univ Bordeaux Segalen, Bordeaux, France
| | - Marie Metzger
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif, France
| | - Ziad A Massy
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif, France
- Department of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt, Paris, France
| | - Sophie Liabeuf
- MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France
- Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens, France
| | - Solène M Laville
- MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France
- Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens, France
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Xie JZ, Huang Y, Zheng XF, Feng R, Li XY, Zheng ZG, Jiang BJ, Du S, Chen HG, Xu Y. The association between serum magnesium and chronic kidney disease in Chinese adults: a cross-sectional study. BMC Public Health 2024; 24:187. [PMID: 38225595 PMCID: PMC10790542 DOI: 10.1186/s12889-023-17615-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 12/29/2023] [Indexed: 01/17/2024] Open
Abstract
BACKGROUND Magnesium (Mg) is both an essential macro-element and a known catalyst, and it plays a vital role in various physiological activities and mechanisms in relation to chronic kidney disease (CKD). However, epidemiological evidence involving this is limited and not entirely consistent. This study aims to explore the association of serum Mg concentrations with the risk of CKD among general Chinese adults. METHODS A total of 8,277 Chinese adults were included in the wave of 2009 from the China Health and Nutrition Survey (CHNS). The primary outcome was the risk of CKD, which was defined as the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Multivariable logistic regression model was used to examine the relationship of serum Mg concentrations with the risk of CKD. RESULTS Included were 8,277 individuals, with an overall CKD prevalence of 11.8% (n = 977). Compared with the first quartile of serum Mg, the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for participants in the second, third, and fourth quartiles of serum Mg were 0.74 (0.58, 0.93), 0.87 (0.69, 1.11) and 1.29 (1.03, 1.61), respectively. Similar results were observed in our several sensitivity analyses. Restricted cubic spline analysis demonstrated a nonlinear (similar "J"-shaped) association between serum Mg concentrations and the risk of CKD (Pnonlinearity <0.001), with a threshold at around a serum Mg value of 2.2 mg/dL. CONCLUSIONS Our results suggested a similar "J"-shaped association between serum Mg concentration and the risk of CKD among Chinese adults. Further large prospective studies are needed to verify these findings.
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Affiliation(s)
- Jing-Zhi Xie
- Department of Nephrology, Blood Purification Research Center, First Affiliated Hospital, Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, Fujian Medical University, Chazhong Road 20, 350005, Fuzhou, Fujian Province, China
- Department of Nephrology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, 350212, Fuzhou, China
| | - Yuanyuan Huang
- Department of Public Health, Fujian Normal University Hospital, Fujian Normal University, Fuzhou, Fujian Province, China
| | - Xiao-Feng Zheng
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Ruimei Feng
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Xiao-Yun Li
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Zi-Gui Zheng
- Department of Nephrology, Blood Purification Research Center, First Affiliated Hospital, Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, Fujian Medical University, Chazhong Road 20, 350005, Fuzhou, Fujian Province, China
- Department of Nephrology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, 350212, Fuzhou, China
| | - Bing-Jing Jiang
- Department of Nephrology, Blood Purification Research Center, First Affiliated Hospital, Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, Fujian Medical University, Chazhong Road 20, 350005, Fuzhou, Fujian Province, China
- Department of Nephrology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, 350212, Fuzhou, China
| | - Shanshan Du
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Heng-Gui Chen
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, No. 1 Xuefu North Rd, 350122, Fuzhou, Fujian Province, China.
| | - Yanfang Xu
- Department of Nephrology, Blood Purification Research Center, First Affiliated Hospital, Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, Fujian Medical University, Chazhong Road 20, 350005, Fuzhou, Fujian Province, China.
- Department of Nephrology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, 350212, Fuzhou, China.
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12
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Suzuki K, Watanabe A, Kiryu Y, Inoue E, Momo K. Self-controlled Case Series Study for Acute Kidney Injury after Starting Proton Pump Inhibitors or Potassium-Competitive Acid Blocker in Patients with Cancer Using a Large Claims Database. Biol Pharm Bull 2024; 47:518-526. [PMID: 38403662 DOI: 10.1248/bpb.b23-00676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2024]
Abstract
To investigate the risk of acute kidney injury (AKI) in patients with cancer following the initiation of proton pump inhibitors (PPIs) and potassium-competitive acid blocker (PCAB), considering sex and anti-cancer drug use. We conducted a self-controlled case-series study using the Japan Medical Data Center claims data from 12422 patients with cancer who were prescribed PPIs or PCAB between January 2017 and December 2019. Considering the timing of PPI or PCAB, control period (days -120 to -1), risk period 1 (days 0 to +30), and risk period 2 (days +31 to +365) were defined. To assess the incidence rate ratio (IRR) and 95% confidence interval (CI) as the risk ratio, we adjusted for anti-cancer drugs to assess the risk of AKI. Additionally, we also examined sex differences to identify the risk of AKI. AKI was observed in risk period 1 [2.05 (1.12-3.72), p = 0.0192], but a slight reduction was noted in risk period 2 [0.60 (0.36-1.00), p = 0.0481]. A sex-specific increase in the risk of AKI was observed only in males during risk period 1 [2.18 (1.10-4.32), p = 0.0260], with a reduction in risk period 2 [0.48 (0.26-0.89), p = 0.0200]. We identified an increased risk of AKI in patients with cancer starting PPIs or PCAB particularly in males within 30 d after PPI or PCAB initiation, emphasizing the need for vigilant monitoring and management of AKI in this patient population.
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Affiliation(s)
- Kosuke Suzuki
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University
- Department of Pharmacy, Showa University Hospital
| | - Ayako Watanabe
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University
- Department of Pharmacy, Showa University Koto Toyosu Hospital
| | - Yoshihiro Kiryu
- Department of Pharmacy, M&B Collaboration Medical corporation Hokuetsu Hospital
| | - Eisuke Inoue
- Showa University Research Administration Center, Showa University
| | - Kenji Momo
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University
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13
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Ansu Baidoo VY, Cara KC, Dickinson SL, Brown AW, Wallace TC, Chung M, Gletsu-Miller N. Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations. J Nutr 2023; 153:3458-3471. [PMID: 37844840 DOI: 10.1016/j.tjnut.2023.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 09/14/2023] [Accepted: 10/03/2023] [Indexed: 10/18/2023] Open
Abstract
BACKGROUND There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of the status of circulating iMg2+ for the screening of populations. OBJECTIVES We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. METHODS We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean. RESULTS A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease. CONCLUSIONS Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.
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Affiliation(s)
| | - Kelly C Cara
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, United States
| | - Stephanie L Dickinson
- School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
| | - Andrew W Brown
- University of Arkansas for Medical Sciences, Little Rock, AR, United States; Arkansas Children's Research Institute, Little Rock, AR, United States
| | - Taylor C Wallace
- Department of Nutrition and Food Studies, George Mason University, Fairfax, VA, United States; Think Healthy Group, Inc., Washington, DC, United States; Center for Magnesium Education & Research, Pahoa, HI, United States
| | - Mei Chung
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, United States
| | - Nana Gletsu-Miller
- School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States.
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14
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Segev A, Shechter M, Tsur AM, Belkin D, Cohen H, Sharon A, Morag NK, Grossman E, Maor E. Serum Magnesium Is Associated with Long-Term Survival of Non-ST-Elevation Myocardial Infarction Patients. Nutrients 2023; 15:4299. [PMID: 37836583 PMCID: PMC10574643 DOI: 10.3390/nu15194299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 10/05/2023] [Accepted: 10/07/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND Low serum magnesium (sMg) is associated with cardiovascular risk factors and atherosclerotic disease. OBJECTIVE To evaluate the association between sMg levels on admission and clinical outcomes in hospitalized non-ST-elevation myocardial infarction (NSTEMI) patients. METHODS A retrospective analysis of all patients admitted to a single tertiary center with a primary diagnosis of NSTEMI. Patients with advanced chronic kidney disease were excluded. Clinical data were collected and compared between lower sMg quartile patients (Q1; sMg < 1.9 mg/dL) and all other patients (Q2-Q4; sMg ≥ 1.9 mg/dL). RESULTS The study cohort included 4552 patients (70% male, median age 69 [IQR 59-79]) who were followed for a median of 4.4 (IQR 2.4-6.6) years. The median sMg level in the low sMg group was 1.7 (1.6-1.8) and 2.0 (2.0-2.2) mg/dL in the normal/high sMg group. The low sMg group was older (mean of 72 vs. 67 years), less likely to be male (64% vs. 72%), and had higher rates of comorbidities, including diabetes, hypertension, and atrial fibrillation (59% vs. 29%, 92% vs. 85%, and 6% vs. 5%; p < 0.05 for all). Kaplan-Meier survival analysis demonstrated significantly higher cumulative death probability at 4 years in the low sMg group (34% vs. 22%; p log rank <0.001). In a multivariable analysis model adjusted for sex, significant comorbidities, coronary interventions during the hospitalization, and renal function, the low sMg group exhibited an independent 24% increased risk of death during follow up (95% CI 1.11-1.39; p < 0.001). CONCLUSIONS Low sMg is independently associated with higher risk of long-term mortality among patients recovering from an NSTEMI event.
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Affiliation(s)
- Amitai Segev
- The Leviev Cardiothoracic & Vascular Center, Sheba Medical Center, Ramat Gan 5262504, Israel; (M.S.); (E.M.)
- The Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel (D.B.); (H.C.); (E.G.)
| | - Michael Shechter
- The Leviev Cardiothoracic & Vascular Center, Sheba Medical Center, Ramat Gan 5262504, Israel; (M.S.); (E.M.)
- The Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel (D.B.); (H.C.); (E.G.)
| | - Avishai M. Tsur
- The Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel (D.B.); (H.C.); (E.G.)
- Department of Medicine, Sheba Medical Center, Ramat Gan 5262504, Israel
- Israel Defense Forces, Medical Corps, Ramat Gan 5262504, Israel
| | - David Belkin
- The Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel (D.B.); (H.C.); (E.G.)
| | - Hofit Cohen
- The Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel (D.B.); (H.C.); (E.G.)
- The Bert W. Strassburger Lipid Center, Sheba Medical Center, Ramat Gan 5262504, Israel
| | - Amir Sharon
- The Leviev Cardiothoracic & Vascular Center, Sheba Medical Center, Ramat Gan 5262504, Israel; (M.S.); (E.M.)
- The Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel (D.B.); (H.C.); (E.G.)
| | - Nira Koren Morag
- The Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel (D.B.); (H.C.); (E.G.)
| | - Ehud Grossman
- The Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel (D.B.); (H.C.); (E.G.)
- Department of Medicine, Sheba Medical Center, Ramat Gan 5262504, Israel
| | - Elad Maor
- The Leviev Cardiothoracic & Vascular Center, Sheba Medical Center, Ramat Gan 5262504, Israel; (M.S.); (E.M.)
- The Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel (D.B.); (H.C.); (E.G.)
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15
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Dos Santos AS, de Menezes ST, Silva IR, Oliveira WN, Pereira ML, Mill JG, Barreto SM, Figueiredo RC. Kidney function decline associated with proton pump inhibitors: results from the ELSA-Brasil cohort. BMC Nephrol 2023; 24:285. [PMID: 37770872 PMCID: PMC10538238 DOI: 10.1186/s12882-023-03300-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 08/16/2023] [Indexed: 09/30/2023] Open
Abstract
OBJECTIVE Investigate the longitudinal association of use and time of use of proton pump inhibitors (PPI) with incidence of chronic kidney disease (CKD) and kidney function change. METHODS Prospective study with 13,909 participants from baseline (2008-2010) and second wave (2012-2014) of the ELSA-Brasil (mean interval between visits = 3.9 years (1.7-6.0)). Participants answered about use and time use of the PPI in the two weeks prior the interview. Renal function was assessed by glomerular filtration rate estimated by the Collaboration Equation for the Epidemiology of Chronic Kidney Disease. Values below 60ml/min/1.73 m² in wave 2 were considered incident CKD. Associations between PPI use and time of use at baseline and incident CKD and decline in renal function were estimated, respectively, by logistic regression and linear models with mixed effects, after adjusting for confounders. RESULTS After adjustments, PPI users for more than six months had an increased risk of CKD compared to non-users. Compared to non-users, users PPIs for up to six months and above six months had greater decline in kidney function over time. CONCLUSION This cohort of adults and elderly, after a mean interval of 3.9 years, PPI use and initial duration were associated with kidney function change between visits.
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Affiliation(s)
- Andrêza Soares Dos Santos
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil
| | - Sara Teles de Menezes
- Longitudinal Study of Adult Health - ELSA-Brasil, Medical School & Clinical Hospital/EBSERH, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Isabella Ribeiro Silva
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil
| | - William Neves Oliveira
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil
| | - Mariana Linhares Pereira
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil
| | - José Geraldo Mill
- Department of Physiological Sciences & University Hospital, Universidade Federal do Espírito Santo, Vitória, Brazil
| | - Sandhi Maria Barreto
- Medical School & Clinical Hospital/EBSERH, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Roberta Carvalho Figueiredo
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil.
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16
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Segev A, Sagir A, Matetzky S, Segev A, Atar S, Shechter M. Admission Serum Magnesium Levels Is Associated with Short and Long-Term Clinical Outcomes in COVID-19 Patients. Nutrients 2023; 15:2016. [PMID: 37432174 PMCID: PMC10180728 DOI: 10.3390/nu15092016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 04/19/2023] [Accepted: 04/20/2023] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND In the face of the global pandemic that the coronavirus disease 2019 (COVID-19) has created, readily available prognostic markers may be of great use. OBJECTIVE To evaluate the association between serum magnesium (sMg) levels on admission and clinical outcomes in hospitalized COVID-19 patients. METHODS We retrospectively analyzed all patients admitted to a single tertiary center with a primary de novo diagnosis of COVID-19. Patients were followed for a mean of 10 ± 7 months. Demographic, clinical and laboratory data were collected and compared between five groups of patients according to sMg quintiles on hospital admission. RESULTS The cohort included 1522 patients (58% male, 69 ± 17 years old). A low sMg level (1st quintile) was associated with higher rates of diabetes and steroid use, whereas a high sMg level (5th quintile) was associated with dyslipidemia, renal dysfunction, higher levels of inflammatory markers and stay in the intensive care unit. All-cause in-hospital and long-term mortality was higher in patients with both low and high sMg levels, compared with mid-range sMg levels (2nd, 3rd and 4th quintiles; 19% and 30% vs. 9.5%, 10.7% and 17.8% and 35% and 45.3% vs. 23%, 26.8% and 27.3% respectively; p < 0.001 for all). After adjusting for significant clinical parameters indicating severe disease and renal dysfunction, only low sMg state was independently associated with increased mortality (HR = 1.57, p < 0.001). CONCLUSIONS Both low and high sMg levels were associated with increased mortality in a large cohort of hospitalized COVID-19 patients. However, after correction for renal dysfunction and disease severity, only low sMg maintained its prognostic ability.
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Affiliation(s)
- Amitai Segev
- The Leviev Cardiothoracic & Vascular Center, Chaim Sheba Medical Center, Ramat Gan 5236723, Israel; (S.M.); (A.S.); (M.S.)
- The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Adam Sagir
- Cardiovascular Division, Galilee Medical Center, Nahariya 2210001, Israel; (A.S.); (S.A.)
- Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan 5290002, Israel
| | - Shlomi Matetzky
- The Leviev Cardiothoracic & Vascular Center, Chaim Sheba Medical Center, Ramat Gan 5236723, Israel; (S.M.); (A.S.); (M.S.)
- The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Amit Segev
- The Leviev Cardiothoracic & Vascular Center, Chaim Sheba Medical Center, Ramat Gan 5236723, Israel; (S.M.); (A.S.); (M.S.)
- The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Shaul Atar
- Cardiovascular Division, Galilee Medical Center, Nahariya 2210001, Israel; (A.S.); (S.A.)
- Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan 5290002, Israel
| | - Michael Shechter
- The Leviev Cardiothoracic & Vascular Center, Chaim Sheba Medical Center, Ramat Gan 5236723, Israel; (S.M.); (A.S.); (M.S.)
- The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
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17
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Macías Ruiz MDC, Cuenca Bermejo L, Veronese N, Fernández Villalba E, González Cuello AM, Kublickiene K, Raparelli V, Norris CM, Kautzky-Willer A, Pilote L, Barbagallo M, Dominguez L, Herrero MT. Magnesium in Kidney Function and Disease-Implications for Aging and Sex-A Narrative Review. Nutrients 2023; 15:1710. [PMID: 37049550 PMCID: PMC10097335 DOI: 10.3390/nu15071710] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/22/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023] Open
Abstract
Magnesium (Mg) has a vital role in the human body, and the kidney is a key organ in the metabolism and excretion of this cation. The objective of this work is to compile the available evidence regarding the role that Mg plays in health and disease, with a special focus on the elderly population with chronic kidney disease (CKD) and the eventual sex differences. A narrative review was carried out by executing an exhaustive search in the PubMed, Scopus, and Cochrane databases. Ten studies were found in which the role of Mg and sex was evaluated in elderly patients with CKD in the last 10 years (2012-2022). The progression of CKD leads to alterations in mineral metabolism, which worsen as the disease progresses. Mg can be used as a coadjuvant in the treatment of CKD patients to improve glomerular filtration, but its use in clinical applications needs to be further characterized. In conclusion, there's a need for well-designed prospective clinical trials to advise and standardize Mg supplementation in daily clinical practice, taking age and sex into consideration.
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Affiliation(s)
- María del Carmen Macías Ruiz
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
| | - Lorena Cuenca Bermejo
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
| | - Nicola Veronese
- Geriatric Unit, Department of Medicine, University of Palermo, 90100 Palermo, Italy
| | - Emiliano Fernández Villalba
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
| | - Ana María González Cuello
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
| | - Karolina Kublickiene
- Department of Renal Medicine, Institution for Clinical Science, Intervention and Technology, Karolinska Institute, 17177 Stockholm, Sweden
| | - Valeria Raparelli
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
| | - Colleen M. Norris
- Faculty of Nursing, University of Alberta, Edmonton, AB T6G 2R3, Canada
- Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services, Edmonton, AB T5J 3E4, Canada
| | - Alexandra Kautzky-Willer
- Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria
| | - Louise Pilote
- Research Institute of McGill University Health Centre, Divisions of General Internal Medicine and Clinical Epidemiology, McGill University, Montreal, QC H4A 3J1, Canada
| | - Mario Barbagallo
- Geriatric Unit, Department of Medicine, University of Palermo, 90100 Palermo, Italy
| | - Ligia Dominguez
- Geriatric Unit, Department of Medicine, University of Palermo, 90100 Palermo, Italy
- Faculty of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy
| | - María Trinidad Herrero
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
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18
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Han CT, Islam MM, Poly TN, Lu YC, Lin MC. A Meta-Analysis of Proton Pump Inhibitor Use and the Risk of Acute Kidney Injury: Geographical Differences and Associated Factors. J Clin Med 2023; 12:jcm12072467. [PMID: 37048551 PMCID: PMC10095047 DOI: 10.3390/jcm12072467] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/11/2023] [Accepted: 03/16/2023] [Indexed: 04/14/2023] Open
Abstract
Proton pump inhibitors (PPIs) are widely prescribed in medical practice for the treatment of several gastrointestinal disorders. Previous epidemiology studies have reported the association between PPI use and the risk of AKI, although the magnitude of the association between PPIs and the risk of acute kidney injury (AKI) remains uncertain. Therefore, we conducted a meta-analysis to determine the relationship between PPI therapy and the risk of AKI. We systematically searched for relevant articles published before January 2023 on PubMed, Scopus, and Web of Science. In addition, we conducted a manual search of the bibliographies of potential articles. Two independent reviewers examined the appropriateness of all studies for inclusion. We pooled studies that compared the risk of AKI with PPI against their control using a random effect model. The search criteria based on PRISMA guidelines yielded 568 articles. Twelve observational studies included 2,492,125 individuals. The pooled adjusted RR demonstrated a significant positive association between PPI therapy and the risk of AKI (adjusted RR 1.75, 95% CI: 1.40-2.19, p < 0.001), and it was consistent across subgroups. A visual presentation of the funnel plot and Egger's regression test showed no evidence of publication bias. Our meta-analysis indicated that persons using PPIs exhibited an increased risk of AKI. North American individuals had a higher risk of AKI compared to Asian and European individuals. However, the pooled effect from observational studies cannot clarify whether the observed association is a causal effect or the result of some unmeasured confounding factors. Hence, the biological mechanisms underlying this association are still unclear and require further research.
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Affiliation(s)
- Cheng Ta Han
- Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan
| | - Md Mohaimenul Islam
- International Center for Health Information Technology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Tahmina Nasrin Poly
- International Center for Health Information Technology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Yu-Chun Lu
- Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan
| | - Ming-Chin Lin
- Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
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Impact of magnesium sulfate therapy in improvement of renal functions in high fat diet-induced diabetic rats and their offspring. Sci Rep 2023; 13:2273. [PMID: 36755074 PMCID: PMC9908981 DOI: 10.1038/s41598-023-29540-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 02/06/2023] [Indexed: 02/10/2023] Open
Abstract
The role of magnesium sulfate (MgSO4) administration to prevent diabetic nephropathy (DN) by reducing insulin resistance (IR) and the relationship of this action with gender and the expression of NOX4 and ICAM1 genes in the parents and their offspring were studied. Males and females rat, and their pups were used. Type 2 diabetes induced by high-fat diet (HFD) administration and a low dose of streptozotocin. Animals were divided into the: non-treated diabetic (DC), the diabetic group received insulin (Ins), and the diabetic group received MgSO4. Two groups of parents received just a normal diet (NDC). Following each set of parents for 16 weeks and their pups for 4 months, while eating normally. We assessed the amount of water consumed, urine volume, and blood glucose level. The levels of glucose, albumin, and creatinine in the urine were also measured, as well as the amounts of sodium, albumin, and creatinine in the serum. Calculations were made for glomerular filtration rate (GFR) and the excretion rates of Na and glucose fractions (FE Na and FE G, respectively). The hyperinsulinemic-euglycemic clamp was done. NOX4 and ICAM1 gene expressions in the kidney were also measured. MgSO4 or insulin therapy decreased blood glucose, IR, and improved GFR, FE Na, and FE G in both parents and their offspring compared to D group. MgSO4 improved NOX4 and ICAM1 gene expressions in the parents and their offspring compared to D group. Our results indicated that MgSO4 could reduce blood glucose levels and insulin resistance, and it could improve kidney function.
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Pannoi T, Promchai C, Apiromruck P, Wongpraphairot S, Yang CC, Pan WC. Estimates of Chronic Kidney Diseases Associated with Proton-Pump Inhibitors Using a Retrospective Hospital-Based Cohort in Thailand. Int J Nephrol Renovasc Dis 2022; 15:371-381. [PMID: 36530347 PMCID: PMC9753254 DOI: 10.2147/ijnrd.s389238] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 12/01/2022] [Indexed: 02/07/2024] Open
Abstract
PURPOSE Potential adverse outcomes of Proton pump inhibitors (PPIs) have increasingly been reported. The potential risks to PPIs include hypomagnesemia and chronic kidney disease (CKD). Unlike a real-world electronic medical record (RW-EMR) with active-comparator design, claim databases and special population cohort with non-user design, using in previous studies, resulted in a wide range of strength of association with indication bias. This study aimed to measure the total effect of association between PPIs use and CKD incidence using Thai RW-EMR. PATIENTS AND METHODS A retrospective hospital-based cohort was applied into this study. Electronic medical records and administrative data of out- and inpatient were retrieved from October 1st, 2010 to September 30th, 2017. On-treatment with grace period as well as propensity score matching was used in data analysis. Cox proportional hazard models were applied to evaluate the PPIs-CKD association. RESULTS Of all 63,595 participants, a total of 59,477 new PPIs and 4118 Histamine 2-receptor antagonist (H2RA) users were eligible for follow-up. As compared with H2RA, the PPI users were non-elderly and more likely being female. The association of PPIs with CKD was statistically significant (adjusted hazard ratio [HR] = 3.753, 95% CI = 2.385-5.905). The HR were not statistically different by concomitant use PPIs with NSAIDs and by medication possession ratio levels. CONCLUSION The association between PPIs and CKD incidence was statistically significant in this hospital-based cohort. However, self-treatment with over-the-counter PPIs, as well as, smoking, drinking alcohol and body mass index could not be fully retrieved, affecting the estimation of treatment effect.
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Affiliation(s)
- Tanavij Pannoi
- International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei City, Taiwan
- Department of Pharmaceutical Care, School of Pharmacy, Walailak University, Nakhon-Si-Thammarat, Thailand
| | - Chissanupong Promchai
- Department of Pharmacy, Songklanagarind Hospital, Prince of Songkla University, Songkla, Thailand
| | - Penjamaporn Apiromruck
- Department of Pharmacy, Songklanagarind Hospital, Prince of Songkla University, Songkla, Thailand
| | - Suwikran Wongpraphairot
- Department of Nephrology Unit, Songklanagarind Hospital, Prince of Songkla University, Songkla, Thailand
| | - Chen-Chang Yang
- International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei City, Taiwan
- Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, Taipei City, Taiwan
- Department of Occupational Medicine and Clinical Toxicology, Taipei Veteran General Hospital, Taipei City, Taiwan
| | - Wen-Chi Pan
- International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei City, Taiwan
- Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, Taipei City, Taiwan
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Xu Q, Hu L, Chen L, Li H, Tian X, Zuo Y, Zhang Y, Zhang X, Sun P, Wang Y, Meng X, Wang A. Low serum magnesium is associated with poor functional outcome in acute ischemic stroke or transient ischemic attack patients. CNS Neurosci Ther 2022; 29:842-854. [PMID: 36415111 PMCID: PMC9928556 DOI: 10.1111/cns.14020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 09/12/2022] [Accepted: 10/16/2022] [Indexed: 11/24/2022] Open
Abstract
AIM The association between magnesium and outcomes after stroke is uncertain. We aimed to investigate the association of serum magnesium with all-cause mortality and poor functional outcome. METHODS We included patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the China National Stroke Registry III. We used Cox proportional hazards model for all-cause mortality and logistic regression model for poor functional outcome (modified Rankin Scale [mRS] 2-6/3-6) to examine the relationships. RESULTS Among the 6483 patients, the median (interquartile range) magnesium was 0.87 (0.80-0.93) mmol/L. Patients in the first quartile had a higher risk of mRS score 3-6/2-6 at 3 months (adjusted odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.02, 1.64; adjusted OR: 1.29; 95% CI: 1.04-1.59) compared with those in the fourth quartile. Similar results were found for mRS score 26 at 1 year. The age- and sex-adjusted hazard ratio (HR) with 95% CI in first quartile magnesium was 1.40 (1.02-1.93) for all-cause mortality within 1 year, but became insignificant (HR: 1.03; 95% CI: 0.71-1.50) after adjusting for potential variables. CONCLUSIONS Low serum magnesium was associated with a high risk of poor functional outcome in patients with AIS or TIA.
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Affiliation(s)
- Qin Xu
- Department of Neurology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina,China National Clinical Research Center for Neurological DiseasesBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
| | - Lele Hu
- The Second People's Hospital of GuiyangGuizhouChina
| | - Lu Chen
- Department of NeurologyZiBo Central HospitalZiboChina
| | - Hao Li
- Department of Neurology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina,China National Clinical Research Center for Neurological DiseasesBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
| | - Xue Tian
- Department of Epidemiology and Health StatisticsSchool of Public Health, Capital Medical UniversityBeijingChina,Beijing Municipal Key Laboratory of Clinical EpidemiologyBeijingChina
| | - Yingting Zuo
- Department of Epidemiology and Health StatisticsSchool of Public Health, Capital Medical UniversityBeijingChina,Beijing Municipal Key Laboratory of Clinical EpidemiologyBeijingChina
| | - Yijun Zhang
- Department of Neurology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina,China National Clinical Research Center for Neurological DiseasesBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
| | - Xiaoli Zhang
- Department of Neurology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina,China National Clinical Research Center for Neurological DiseasesBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
| | - Ping Sun
- The Second People's Hospital of GuiyangGuizhouChina
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina,China National Clinical Research Center for Neurological DiseasesBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina,Advanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijingChina,Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghaiChina
| | - Xia Meng
- Department of Neurology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina,China National Clinical Research Center for Neurological DiseasesBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
| | - Anxin Wang
- Department of Neurology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina,China National Clinical Research Center for Neurological DiseasesBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
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22
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Long M, Zhu X, Wei X, Zhao D, Jiang L, Li C, Jin D, Miao C, Du Y. Magnesium in renal fibrosis. Int Urol Nephrol 2022; 54:1881-1889. [PMID: 35060008 DOI: 10.1007/s11255-022-03118-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 01/11/2022] [Indexed: 12/12/2022]
Abstract
PURPOSE Renal fibrosis (RF) is the main pathological feature of chronic kidney disease (CKD). The main focus of research on treatment for CKD is to develop strategies that delay or prevent RF from progressing to end-stage renal disease (ESRD). Inflammation and oxidative stress occur during all stages of CKD. The magnesium cation (Mg2+) can reduce inflammation and oxidative stress, regulate apoptosis, and improve RF, and magnesium-based therapies are promising new treatments that can prevent RF. We reviewed the current evidence on the effects of magnesium in RF and examined the possible mechanism of magnesium in delaying RF. METHODS We searched PubMed, Web of Science, and EMBASE for articles on magnesium and fibrosis, with a focus on magnesium and RF. RESULTS Inflammation, oxidative stress, and apoptosis are related to the occurrence of CKD. Previous research showed that Mg2+ inhibits the differentiation of inflammatory cells, down-regulates the production of inflammatory cytokines, reduces inflammation, and reduces the production of reactive oxygen species (ROS) and oxidative stress. In addition, Mg2+ also regulates apoptosis and protects renal tubular function. Magnesium may also regulate TRPM6/7, promote the secretion of klotho protein and improve renal fibrosis. Therefore, Mg2+ can protect the kidney from damage and slow down the progression of RF through many molecular and cellular effects. Some of the anti-fibrotic effects of Mg2+ may be related to its antagonism of intracellular Ca2+. CONCLUSION Magnesium may prevent the progression of renal fibrosis and delay CKD by reducing renal inflammation and oxidative stress, and by regulating fibrosis-related signaling pathways and cytokines.
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Affiliation(s)
- Mengtuan Long
- Department of Nephrology, The First Hospital of Jilin University, 1 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China
| | - Xiaoyu Zhu
- Department of Nephrology, The First Hospital of Jilin University, 1 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China
| | - Xuejiao Wei
- Department of Nephrology, The First Hospital of Jilin University, 1 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China
| | - Dan Zhao
- Department of Nephrology, The First Hospital of Jilin University, 1 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China
| | - Lili Jiang
- Physical Examination Center, The First Hospital of Jilin University, 1 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China
| | - Chenhao Li
- Department of Nephrology, The First Hospital of Jilin University, 1 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China
| | - Die Jin
- Department of Nephrology, The First Hospital of Jilin University, 1 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China
| | - Changxiu Miao
- Department of Nephrology, The First Hospital of Jilin University, 1 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China
| | - Yujun Du
- Department of Nephrology, The First Hospital of Jilin University, 1 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China.
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Kooijmans ECM, van der Pal HJH, Pluijm SMF, van der Heiden-van der Loo M, Kremer LCM, Bresters D, van Dulmen-den Broeder E, van den Heuvel-Eibrink MM, Loonen JJ, Louwerens M, Neggers SJC, Ronckers C, Tissing WJE, de Vries ACH, Kaspers GJL, Bökenkamp A, Veening MA. Long-Term Tubular Dysfunction in Childhood Cancer Survivors; DCCSS-LATER 2 Renal Study. Cancers (Basel) 2022; 14:2754. [PMID: 35681735 PMCID: PMC9179377 DOI: 10.3390/cancers14112754] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/13/2022] [Accepted: 05/17/2022] [Indexed: 11/29/2022] Open
Abstract
The aim of this nationwide cross-sectional cohort study was to determine the prevalence of and risk factors for tubular dysfunction in childhood cancer survivors (CCS). In the DCCSS-LATER 2 Renal study, 1024 CCS (≥5 years after diagnosis), aged ≥ 18 years at study, treated between 1963 and 2001 with potentially nephrotoxic therapy (i.e., nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide, or hematopoietic stem cell transplantation) participated, and 500 age- and sex-matched participants from Lifelines acted as controls. Tubular electrolyte loss was defined as low serum levels (magnesium < 0.7 mmol/L, phosphate < 0.7 mmol/L and potassium < 3.6 mmol/L) with increased renal excretion or supplementation. A α1-microglobulin:creatinine ratio > 1.7 mg/mmol was considered as low-molecular weight proteinuria (LMWP). Multivariable risk analyses were performed. After median 25.5 years follow-up, overall prevalence of electrolyte losses in CCS (magnesium 5.6%, potassium 4.5%, phosphate 5.5%) was not higher compared to controls. LMWP was more prevalent (CCS 20.1% versus controls 0.4%). LMWP and magnesium loss were associated with glomerular dysfunction. Ifosfamide was associated with potassium loss, phosphate loss (with cumulative dose > 42 g/m2) and LMWP. Cisplatin was associated with magnesium loss and a cumulative dose > 500 mg/m2 with potassium and phosphate loss. Carboplatin cumulative dose > 2800 mg/m2 was associated with potassium loss. In conclusion, long-term tubular dysfunction is infrequent. Yet, ifosfamide, cisplatin and carboplatin are risk factors.
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Affiliation(s)
- Esmee C. M. Kooijmans
- Department of Pediatric Oncology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; (E.v.D.-d.B.); (G.J.L.K.); (M.A.V.)
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
| | - Helena J. H. van der Pal
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
| | - Saskia M. F. Pluijm
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
| | - Margriet van der Heiden-van der Loo
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
- Dutch Childhood Oncology Group, 3584 CS Utrecht, The Netherlands
| | - Leontien C. M. Kremer
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
- Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands
- Deparmtnet of Pediatric Oncology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - Dorine Bresters
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
- Willem Alexander Children’s Hospital, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Eline van Dulmen-den Broeder
- Department of Pediatric Oncology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; (E.v.D.-d.B.); (G.J.L.K.); (M.A.V.)
| | - Marry M. van den Heuvel-Eibrink
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
- Department of Pediatric Oncology, Sophia Children’s Hospital, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands
| | - Jacqueline J. Loonen
- Department of Hematology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;
| | - Marloes Louwerens
- Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
| | - Sebastian J. C. Neggers
- Department of Internal Medicine, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands;
| | - Cécile Ronckers
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
| | - Wim J. E. Tissing
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
- Department of Pediatric Oncology, University of Groningen, University Medical Center Groningen, 8713 GZ Groningen, The Netherlands
| | - Andrica C. H. de Vries
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
- Department of Pediatric Oncology, Sophia Children’s Hospital, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands
| | - Gertjan J. L. Kaspers
- Department of Pediatric Oncology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; (E.v.D.-d.B.); (G.J.L.K.); (M.A.V.)
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
| | - Arend Bökenkamp
- Department of Pediatric Nephrology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands;
| | - Margreet A. Veening
- Department of Pediatric Oncology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; (E.v.D.-d.B.); (G.J.L.K.); (M.A.V.)
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.v.d.P.); (S.M.F.P.); (M.v.d.H.-v.d.L.); (L.C.M.K.); (D.B.); (M.M.v.d.H.-E.); (C.R.); (W.J.E.T.); (A.C.H.d.V.)
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Isakov O, Patibandla BK, Christopher KB, Chandraker A, Hod T. Impact of Post-Transplantation Hypomagnesemia on Long-Term Graft and Patient Survival after Transplantation. Kidney Blood Press Res 2022; 47:341-353. [PMID: 35196662 DOI: 10.1159/000522233] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/24/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Post-transplant hypomagnesemia is commonly observed among patients prescribed calcineurin inhibitor (CNIs). METHODS We conducted a retrospective single-center analysis (2000-2013, N = 726) to examine the association of hypomagnesemia with long-term patient and allograft outcomes in kidney transplant recipients. A median serum magnesium (Mg) level of all measured Mg levels from 1 month to 1 year posttransplant was calculated. RESULTS For every increase in Mg of 0.1 mg/dL, the risk for either graft loss or death, overall mortality, and death with a functioning graft increased by 11%, 14%, and 12%, respectively (p < 0.01). In a multivariate model, patients with median Mg level ≥1.7 mg/dL had a reduced overall survival rate (HR 1.57, 95% CI: 1.04-2.38, p = 0.033) compared to those with median Mg level <1.7 mg/dL. This association was observed in subgroups of patients above 60 years old, in those who had a slow graft function (SGF) and in females. CONCLUSIONS Posttransplant hypomagnesemia is associated with better patient and allograft survival up to 10 years posttransplant. This relationship remained significant after accounting for baseline allograft function, presence of SGF and CNI trough levels.
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Affiliation(s)
- Ofer Isakov
- Department of Internal Medicine "T", Tel Aviv Souraski Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Bhanu K Patibandla
- Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon, USA
| | - Kenneth B Christopher
- Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Anil Chandraker
- Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Transplant Research Center, Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Tammy Hod
- Department of Nephrology, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.,Renal Transplant Center, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
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Dent A, Selvaratnam R. Measuring Magnesium – Physiological, Clinical and Analytical Perspectives. Clin Biochem 2022; 105-106:1-15. [DOI: 10.1016/j.clinbiochem.2022.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 03/23/2022] [Accepted: 04/01/2022] [Indexed: 11/03/2022]
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Hou C, Wang Y, Sui X, Yi J, Yao H, Liu W, Yu Z, Xia L, Guo Q, Xin W, Hou Q. The association of serum magnesium and chronic kidney disease: a two-sample mendelian randomization study of European descent. Eur J Clin Nutr 2022; 76:1309-1314. [PMID: 35260827 DOI: 10.1038/s41430-022-01106-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 01/23/2022] [Accepted: 02/16/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Previous observational studies focused on the association of serum magnesium (SMg) and chronic kidney disease (CKD), but the conclusion was inconsistent. To investigate the causal relationship of SMg and CKD, we performed a two-sample mendelian randomization (TSMR) analysis using publicly datasets. METHOD In mendelian randomization (MR) analysis, we used single nucleotide polymorphisms (SNPs) which had genetic statistical significance with SMg but not associated with kidney function and confounding factors as instrumental variable (IV). To select SNPs, we used publicly database of Genome Wide Association Study (GWAS) and Chronic Kidney Disease Genetics (CKDGen) Confirms. We used inverse-variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode approaches in TSMR analysis. RESULTS We selected 4 SNPs (rs4072037, rs7965584, rs11144134 and rs448378) as IV. In IVW approach, the result of MR analysis for CKD was OR = 0.55, 95% CI: 0.06, 4.75, P = 0.58; for estimated glomerular filtration rate from creatinine (eGFR)crea was β = -0.06, 95% CI: -1.08, 0.07, P = 0.39; for estimated glomerular filtration rate from cystatin C (eGFR)cys was β = -0.03, 95% CI: -0.43, 0.36, P = 0.86, respectively per SD increase in SMg. When subgroup by diabetes mellitus (DM), the results for DM-eGFRcrea was β = -0.33, 95% CI: -0.85, 0.19, P = 0.21; and for non-DM-eGFRcrea was β = -0.03, 95% CI: -0.16, 0.11, P = 0.71. The results of other four MR approaches were consistent with IVW approach (all P > 0.05). CONCLUSION Our TSMR analysis showed that SMg had no causal effect on kidney function and progress CKD in European descent. As for the results about overall population, the verified study is needed in future study.
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Affiliation(s)
- Chenyang Hou
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yun Wang
- Department of Public Health and Health Management, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong, China
| | - Xinxia Sui
- Department of Public Health and Health Management, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong, China
| | - Jihu Yi
- Department of Public Health and Health Management, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong, China
| | - Huichen Yao
- Department of Cardiovascular Medicine, The third affiliated hospital of Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong, China
| | - Weihua Liu
- School of Nursing, Shandong First Medical University (Shandong Academy of Medical Sciences), Taian, Shandong, China
| | - Zhiyuan Yu
- Centers for Disease Control and Prevention of Rizhao, Rizhao, Shandong, China
| | - Lichuan Xia
- Zibo Hospital of Integrated Traditional Chinese and Western Medicine, Zibo, Shandong, China
| | - Qing Guo
- Department of Nursing, The second affiliated hospital of Shandong first medical university, Taian, Shandong, China
| | - Wei Xin
- Provincial Hospital affiliated to Shandong First Medical University, Shandong First Medical University Medical Science and Technology Innovation Center, Jinan, Shandong, China.
| | - Qingzhi Hou
- Department of Public Health and Health Management, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong, China.
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Hypermagnesaemia, but Not Hypomagnesaemia, Is a Predictor of Inpatient Mortality in Critically Ill Children with Sepsis. DISEASE MARKERS 2022; 2022:3893653. [PMID: 35126786 PMCID: PMC8814719 DOI: 10.1155/2022/3893653] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 11/25/2021] [Accepted: 01/05/2022] [Indexed: 12/20/2022]
Abstract
Objective The effect of serum magnesium on the prognosis of children with sepsis in the pediatric intensive care unit (PICU) is unclear. This study was designed to assess the risk of inpatient mortality for children with sepsis in the PICU based on serum magnesium levels at admission. Methods We collected patients' clinical information from the Pediatric Intensive Care database and then performed locally weighted scatterplot smoothing (LOWESS) analysis, Kaplan–Meier analysis, and multivariate logistic regression to determine the relationship between admission serum magnesium and inpatient mortality in children with sepsis. Results A total of 974 critically ill children with sepsis were included, with 246 patients in the hypomagnesemia group, 666 in the normal group, and 62 in the hypermagnesemia group. The chi-square test suggested that the hypermagnesemia group had higher in-hospital mortality than the normal group (14.5% vs. 2.4%, P < 0.001). Kaplan–Meier curves revealed that the 30-day overall survival rate was lower in the hypermagnesaemia group than in the normal group (P < 0.001). The multivariate logistic regression model revealed that hypermagnesaemia was a risk factor related to inpatient mortality (odds ratio 4.22, 95% CI 1.55-11.50), while hypomagnesaemia was not a significant factor for inpatient mortality (odds ratio 0.78, 95% CI 0.26-2.32). Conclusion Hypermagnesaemia, but not hypomagnesaemia, is a predictor of inpatient mortality in critically ill children with sepsis.
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Liu H, Wang R. Associations between the serum magnesium and all-cause or cardiovascular mortality in chronic kidney disease and end-stage renal disease patients: A meta-analysis. Medicine (Baltimore) 2021; 100:e27486. [PMID: 34766558 PMCID: PMC8589258 DOI: 10.1097/md.0000000000027486] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/13/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Some studies have found that hypomagnesemia is associated with vascular calcification, atherosclerosis, and cardiovascular disease, which may lead to increased mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) who need to maintain hemodialysis (HD). However, the conclusion of these studies remain controversial. METHODS Relevant literature was retrieved from the database of Cochrane library, PubMed, EMBASE, and CNKI until December 2020, without any language restrictions. The data was analyzed using the Stata 12.0 software. RESULTS A total of 31 studies were included, involving 205436 participants. The results showed that after multivariable adjusted, hypomagnesemia was significant associated with the risk of all-cause mortality in patients with CKD and end-stage renal disease (ESRD) (hazard ratios [HR] 1.955; 95% confidence interval (95% CI) 1.511-2.528; P = .000; hypomagnesemia vs normal magnesium or hypermagnesemia). In contrast, in patients with CKD and ESRD, hypermagnesemia was negatively correlated with all-cause mortality (HR 0.873; 95% CI 0.793-0.960; P = .005) (per unit increase). Moreover, in the adjusted model, it was observed that hypermagnesemia was significantly associated with a reduced risk of cardiovascular death (HR 0.598; 95% CI 0.094-1.102, P = .020). In addition, subgroup analysis found that hypomagnesemia was closely related to the increase of all-cause mortality in HD patients (HR 1.799; 95% CI 1.375-2.354; P = .000) (hypomagnesemia vs normal magnesium or hypermagnesemia). CONCLUSION Our results show that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in maintenance HD patients. Further studies should be conducted to evaluate the benefits of magnesium correction in maintenance dialysis patients with hypomagnesemia.
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Correa S, Guerra-Torres XE, Waikar SS, Mc Causland FR. Serum Magnesium, Blood Pressure, and Risk of Hypertension and Chronic Kidney Disease Progression in the CRIC Study. Hypertension 2021; 78:1771-1780. [PMID: 34757763 DOI: 10.1161/hypertensionaha.121.17694] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
[Figure: see text].
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Affiliation(s)
- Simon Correa
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT (S.C.).,Yale New Haven Hospital, CT (S.C.).,Division of Renal Medicine, Brigham and Women's Hospital. Boston, MA (S.C., F.R.M.C.).,Harvard Medical School, Boston, MA (S.C., F.R.M.C.)
| | - Xavier E Guerra-Torres
- Nephrology Section, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain (X.E.G.-T.)
| | - Sushrut S Waikar
- Section of Nephrology, Department of Medicine, Boston University School of Medicine and Boston Medical Center, MA (S.S.W.)
| | - Finnian R Mc Causland
- Division of Renal Medicine, Brigham and Women's Hospital. Boston, MA (S.C., F.R.M.C.).,Harvard Medical School, Boston, MA (S.C., F.R.M.C.)
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30
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Galán Carrillo I, Vega A, Goicoechea M, Shabaka A, Gatius S, Abad S, López-Gómez JM. Impact of Serum Magnesium Levels on Kidney and Cardiovascular Prognosis and Mortality in CKD Patients. J Ren Nutr 2021; 31:494-502. [DOI: 10.1053/j.jrn.2020.09.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 09/14/2020] [Accepted: 09/23/2020] [Indexed: 02/03/2023] Open
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Liamis G, Hoorn EJ, Florentin M, Milionis H. An overview of diagnosis and management of drug-induced hypomagnesemia. Pharmacol Res Perspect 2021; 9:e00829. [PMID: 34278747 PMCID: PMC8287009 DOI: 10.1002/prp2.829] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 03/18/2021] [Accepted: 06/01/2021] [Indexed: 12/29/2022] Open
Abstract
Magnesium (Mg) is commonly addressed as the "forgotten ion" in medicine. Nonetheless, hypomagnesemia should be suspected in clinical practice in patients with relevant symptomatology and also be considered a predisposing factor for the development of other electrolyte disturbances. Furthermore, chronic hypomagnesemia has been associated with diabetes mellitus and cardiovascular disease. Hypomagnesemia as a consequence of drug therapy is relatively common, with the list of drugs inducing low serum Mg levels expanding. Culprit medications linked to hypomagnesemia include antibiotics (e.g. aminoglycosides, amphotericin B), diuretics, antineoplastic drugs (cisplatin and cetuximab), calcineurin inhibitors, and proton pump inhibitors. In recent years, the mechanisms of drug-induced hypomagnesemia have been unraveled through the discovery of key Mg transporters in the gut and kidney. This narrative review of available literature focuses on the pathogenetic mechanisms underlying drug-induced hypomagnesemia in order to increase the insight of clinicians toward early diagnosis and effective management.
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Affiliation(s)
- George Liamis
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Ewout J Hoorn
- Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Matilda Florentin
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Haralampos Milionis
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
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32
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Lahav I, Steinmetz T, Molcho M, Lev N, Agur T, Nesher E, Rozen-Zvi B, Rahamimov R. The Association Between Exposure to Low Magnesium Blood Levels After Renal Transplantation and Cardiovascular Morbidity and Mortality. Front Med (Lausanne) 2021; 8:690273. [PMID: 34322504 PMCID: PMC8310919 DOI: 10.3389/fmed.2021.690273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 06/10/2021] [Indexed: 11/24/2022] Open
Abstract
Background: Serum magnesium levels are associated with cardiovascular disease and all-cause mortality in the general population and chronic kidney disease patients, but the association between serum magnesium levels and cardiovascular risk after kidney transplantation is not established. We sought to evaluate whether exposure to low serum magnesium levels after renal transplantation is related to cardiovascular morbidity and mortality. Methods: We conducted a single center retrospective study that included all transplanted patients who had a functioning graft for at least 6 months after transplantation between January 2001 and December 2013. We calculated exposure to magnesium using time weighted average for serum magnesium levels, using all values available during the follow-up. Several statistical methods were used, including liner regression analysis, χ2 test, and multivariate Cox proportional hazard model. Results: Four hundred ninety-eight patients were included. Median follow-up was 5.26 years. High time weighted average of serum magnesium was associated with a hazard ratio of 1.94 for all-cause mortality and major cardiovascular outcome compared to low levels (95% CI 1.18–3.19, p = 0.009). The high quartile of time weighted average of serum magnesium was associated with death censored major cardiovascular outcome (hazard ratio 2.13, 95% CI 1.17–3.86, p = 0.013) in multivariate analysis. Conclusions: Exposure to low serum magnesium levels in renal transplant recipients was associated with a lower risk for all-cause mortality and major cardiovascular outcome. These findings contrast the higher risk found in the general population.
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Affiliation(s)
- Itay Lahav
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tali Steinmetz
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel
| | - Maya Molcho
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Neta Lev
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel
| | - Timna Agur
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel
| | - Eviatar Nesher
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Organ Transplantation, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
| | - Benaya Rozen-Zvi
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel
| | - Ruth Rahamimov
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel.,Department of Organ Transplantation, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
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Panthofer AM, Lyu B, Astor BC, Singh T, Aziz F, Mandelbrot D, Parajuli S, Mohamed M, Djamali A, Garg N. Post-kidney transplant serum magnesium exhibits a U-shaped association with subsequent mortality: an observational cohort study. Transpl Int 2021; 34:1853-1861. [PMID: 34081803 DOI: 10.1111/tri.13932] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/10/2021] [Accepted: 05/27/2021] [Indexed: 11/30/2022]
Abstract
Hypomagnesemia is common in kidney transplant recipients (KTRs). We sought to explore the relationship between Mg and outcomes in KTRs, which may be associated with mortality and thus may be a potential intervention target to improve outcomes. We followed KTRs performed between 01/2000 and 6/2016 at a large US transplant center from 6 months post-transplant to graft failure, death, or loss to follow-up. Using Mg as a time-dependent variable, associations between Mg and outcomes any time after 6 months post-transplant were evaluated. 3680 KTRs with 50 413 Mg measurements met inclusion criteria. 657 deaths occurred over a median follow-up of 5.1 years. Compared to Mg of 1.5-1.8 mg/dl, both lower (HR 1.17, 95% confidence interval (CI): 1.07-1.28) and higher (HR 1.16, 95% CI: 1.09-1.23) Mg levels were associated with greater risk of mortality. Similar U-shaped associations were observed for Mg and cardiovascular disease-related mortality (HR for Mg ≤1.5 mg/dl: 1.31; CI: 1.03-1.68) and infection-related mortality (HR for Mg ≤1.5 mg/dl: 1.28; CI: 1.09-1.51), although relationships for Mg >1.8 mg/dl were not statistically significant. Mg exhibits a U-shaped association with mortality in KTRs, with levels between 1.5 and 1.8 mg/dl associated with the lowest risk.
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Affiliation(s)
- Annalise M Panthofer
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Beini Lyu
- Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Brad C Astor
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.,Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Tripti Singh
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Fahad Aziz
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Maha Mohamed
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Arjang Djamali
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.,Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Neetika Garg
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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Hanaoka H, Kikuchi J, Kaneko Y, Seki N, Tsujimoto H, Chiba K, Takeuchi T. Proton Pump Inhibitor and Tacrolimus Uses are Associated With Hypomagnesemia in Connective Tissue Disease: a Potential Link With Renal Dysfunction and Recurrent Infection. Front Pharmacol 2021; 12:616719. [PMID: 34093176 PMCID: PMC8173076 DOI: 10.3389/fphar.2021.616719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 05/10/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Low levels of serum magnesium perturb renal tubular cell function and lymphocytes, resulting in renal deterioration and an imbalance in mononuclear cells. This study investigated the mechanism and influence of hypomagnesemia in patients with connective tissue disease. Methods: We retrospectively evaluated patients with connective tissue disease and available serum magnesium data who visited Keio University Hospital in 2019. Patients were divided into two groups: those with (serum magnesium < 1.8 mg/dl) and those without hypomagnesemia; their rates of hospitalization for severe infection and cumulative renal deterioration were compared. Patients’ fractions of lymphocytes and natural killer and dendritic cell subsets, as measured by fluorescence-activated cell sorting (FACS) analysis, were also compared. Results: Among 284 patients, hypomagnesemia was detected in 63 (22.2%). Multivariate analysis revealed that the use of proton pump inhibitors [odds ratio (OR), 1.48; p = 0.01] and tacrolimus (OR, 6.14; p < 0.01) was independently associated with hypomagnesemia. In addition, the renal deterioration rate was significantly higher in tacrolimus and/or proton pump inhibitor users with hypomagnesemia (p = 0.01). The hospitalization rate for severe infection was also higher in patients with hypomagnesemia (p = 0.04). FACS analysis showed lower CD8+ T cell, CD19+ B cell, natural killer cell, and dendritic cell counts in patients with hypomagnesemia (p = 0.03, p = 0.02, p = 0.02, and p = 0.03, respectively). Conclusion: The use of tacrolimus and proton pump inhibitors may be associated with hypomagnesemia and lead to poor renal outcomes and severe infection in patients with connective tissue disease.
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Affiliation(s)
- Hironari Hanaoka
- Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
| | - Jun Kikuchi
- Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
| | - Yuko Kaneko
- Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
| | - Noriyasu Seki
- Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan
| | | | - Kenji Chiba
- Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan
| | - Tsutomu Takeuchi
- Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
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Negrea L, DeLozier SJ, Janes JL, Rahman M, Dobre M. Serum Magnesium and Cardiovascular Outcomes and Mortality in CKD: The Chronic Renal Insufficiency Cohort (CRIC). Kidney Med 2021; 3:183-192.e1. [PMID: 33851114 PMCID: PMC8039411 DOI: 10.1016/j.xkme.2020.10.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
RATIONALE & OBJECTIVE Low serum magnesium level has been shown to be associated with increased mortality, but its role as a predictor of cardiovascular disease is unclear. This study evaluates the association between serum magnesium level and cardiovascular events and all-cause mortality in a large cohort of individuals with chronic kidney disease (CKD). STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 3,867 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURES Serum magnesium measured at study baseline. OUTCOMES Composite cardiovascular events (myocardial infarction, cerebrovascular accident, heart failure, and peripheral arterial disease) and all-cause mortality. ANALYTICAL APPROACH Cox proportional hazards models adjusted for demographic, clinical, and laboratory characteristics. RESULTS During the 14.6 (4.4) years (standard deviation) of follow-up, 1,384 participants died (36/1,000 person-years), and 1,227 (40/1,000 person-years) had a composite cardiovascular event. There was a nonlinear association between serum magnesium level and all-cause mortality. Low and high magnesium levels were associated with greater rates of all-cause mortality after adjusting for demographics, comorbid conditions, medications including diuretics, estimated glomerular filtration rate, and proteinuria (P < 0.001). No significant associations were observed between serum magnesium levels and the composite cardiovascular events. Low serum magnesium level was associated with incident atrial fibrillation (HR, 1.36; 95% CI, 1.01-1.82; P = 0.04). LIMITATIONS Single measurement of serum magnesium. CONCLUSIONS In this large CKD cohort, serum magnesium level < 1.9 mg/dL and >2.1 mg/dL was associated with increased risk for all-cause mortality. Low magnesium level was associated with incident atrial fibrillation but not with composite cardiovascular disease events. Further studies are needed to determine the optimal range of serum magnesium in CKD to prevent adverse clinical outcomes.
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Affiliation(s)
- Lavinia Negrea
- Division of Nephrology and Hypertension, University Hospital Case Medical Center, Case Western Reserve University, Cleveland, OH
| | | | | | - Mahboob Rahman
- Division of Nephrology and Hypertension, University Hospital Case Medical Center, Case Western Reserve University, Cleveland, OH
- Louis Stokes Cleveland VA Medical Center, Cleveland, OH
| | - Mirela Dobre
- Division of Nephrology and Hypertension, University Hospital Case Medical Center, Case Western Reserve University, Cleveland, OH
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36
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Leenders NHJ, Vermeulen EA, van Ballegooijen AJ, Hoekstra T, de Vries R, Beulens JW, Vervloet MG. The association between circulating magnesium and clinically relevant outcomes in patients with chronic kidney disease: A systematic review and meta-analysis. Clin Nutr 2020; 40:3133-3147. [PMID: 33419615 DOI: 10.1016/j.clnu.2020.12.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 12/05/2020] [Accepted: 12/15/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND & AIMS Despite modern treatment, risk for cardiovascular disease and mortality in patients with chronic kidney disease (CKD) is unacceptably high. Observational studies have shown associations of magnesium with risk for several clinical outcomes in CKD of variable magnitude. The aim of this review is to provide a systematic overview and meta-analysis of longitudinal studies assessing the association of plasma magnesium concentration with clinically relevant outcomes in adult patients with chronic kidney disease, with a minimal follow-up of 6 months. Primary outcomes of interest were all-cause mortality, cardiovascular mortality, cardiovascular events, sudden death and hospitalisation. METHODS The electronic databases PubMed, Embase and The Cochrane Library were searched using terms relating to plasma magnesium and CKD patients, and two authors independently selected eligible studies. Study quality was assessed according to the Newcastle-Ottawa Scale. Results of studies with a comparable magnesium exposure and outcome measure, were pooled using a random-effects meta-regression analysis. RESULTS The search yielded 6156 records of which 33 studies, involving 348,059 patients, met the eligibility criteria. Finally, 22 studies could be included in the meta-analysis. Higher magnesium was associated with a lower risk for all-cause mortality (HR 0.90 [0.87-0.94] per 0.1 mmol/L increase of magnesium) and cardiovascular mortality and events (HR 0.85 [0.77-0.94] per 0.1 mmol/L). CONCLUSIONS Magnesium concentration is inversely associated with all-cause mortality and cardiovascular mortality and events. Therefore, increasing magnesium may improve risk in patients with chronic kidney disease. This meta-analysis forms a firm base for future prospective trials to test whether increasing plasma magnesium, indeed has beneficial effects on clinical outcomes.
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Affiliation(s)
- Nicoline H J Leenders
- Department of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
| | - Emma A Vermeulen
- Department of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Adriana J van Ballegooijen
- Department of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology and Biostatistics, Amsterdam Public Health Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Tiny Hoekstra
- Department of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Ralph de Vries
- Medical Library, Vrije Universiteit Amsterdam, the Netherlands
| | - Joline W Beulens
- Department of Epidemiology and Biostatistics, Amsterdam Public Health Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Marc G Vervloet
- Department of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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Rodelo-Haad C, Pendón-Ruiz de Mier MV, Díaz-Tocados JM, Martin-Malo A, Santamaria R, Muñoz-Castañeda JR, Rodríguez M. The Role of Disturbed Mg Homeostasis in Chronic Kidney Disease Comorbidities. Front Cell Dev Biol 2020; 8:543099. [PMID: 33282857 PMCID: PMC7688914 DOI: 10.3389/fcell.2020.543099] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Accepted: 10/09/2020] [Indexed: 12/19/2022] Open
Abstract
Some of the critical mechanisms that mediate chronic kidney disease (CKD) progression are associated with vascular calcifications, disbalance of mineral metabolism, increased oxidative and metabolic stress, inflammation, coagulation abnormalities, endothelial dysfunction, or accumulation of uremic toxins. Also, it is widely accepted that pathologies with a strong influence in CKD progression are diabetes, hypertension, and cardiovascular disease (CVD). A disbalance in magnesium (Mg) homeostasis, more specifically hypomagnesemia, is associated with the development and progression of the comorbidities mentioned above, and some mechanisms might explain why low serum Mg is associated with negative clinical outcomes such as major adverse cardiovascular and renal events. Furthermore, it is likely that hypomagnesemia causes the release of inflammatory cytokines and C-reactive protein and promotes insulin resistance. Animal models have shown that Mg supplementation reverses vascular calcifications; thus, clinicians have focused on the potential benefits that Mg supplementation may have in humans. Recent evidence suggests that Mg reduces coronary artery calcifications and facilitates peripheral vasodilation. Mg may reduce vascular calcification by direct inhibition of the Wnt/β-catenin signaling pathway. Furthermore, Mg deficiency worsens kidney injury induced by an increased tubular load of phosphate. One important consequence of excessive tubular load of phosphate is the reduction of renal tubule expression of α-Klotho in moderate CKD. Low Mg levels worsen the reduction of Klotho induced by the tubular load of phosphate. Evidence to support clinical translation is yet insufficient, and more clinical studies are required to claim enough evidence for decision-making in daily practice. Meanwhile, it seems reasonable to prevent and treat Mg deficiency. This review aims to summarize the current understanding of Mg homeostasis, the potential mechanisms that may mediate the effect of Mg deficiency on CKD progression, CVD, and mortality.
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Affiliation(s)
- Cristian Rodelo-Haad
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain.,University of Córdoba, Córdoba, Spain.,Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.,Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain
| | - M Victoria Pendón-Ruiz de Mier
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain.,University of Córdoba, Córdoba, Spain.,Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.,Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain
| | - Juan Miguel Díaz-Tocados
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain.,University of Córdoba, Córdoba, Spain
| | - Alejandro Martin-Malo
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain.,University of Córdoba, Córdoba, Spain.,Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.,Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain
| | - Rafael Santamaria
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain.,University of Córdoba, Córdoba, Spain.,Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.,Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain
| | - Juan Rafael Muñoz-Castañeda
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain.,University of Córdoba, Córdoba, Spain.,Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.,Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain
| | - Mariano Rodríguez
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain.,University of Córdoba, Córdoba, Spain.,Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.,Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain
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38
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Hod T, Isakov O, Patibandla BK, Christopher KB, Hershkoviz R, Schwartz IF, Chandraker A. Posttransplantation Hypomagnesemia as a Predictor of Better Graft Function after Transplantation. Kidney Blood Press Res 2020; 45:982-995. [PMID: 33152728 DOI: 10.1159/000510797] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 08/11/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Hypomagnesemia is frequently seen after transplantation and is particularly associated with the use of calcineurin inhibitors (CNIs). METHODS We conducted a retrospective, single-center analysis (2000-2013, N = 726) to explore the relationship between hypomagnesemia and long-term allograft outcome in kidney transplant recipients. For this study, a median serum magnesium (Mg) level of all measured Mg levels from 1 month to 1 year after renal transplantation was calculated. RESULTS For every increase in Mg by 0.1 mg/dL, the GFR decreased by 1.1 mL/min at 3 years posttransplant (p < 0.01) and by 1.5 mL/min at 5 years posttransplant. A median blood Mg level of ≥1.7 was found to be an independent predictor of a GFR <60 mL/min at 3 years posttransplant. The odds of having a GFR <60 mL/min 3 years posttransplant was almost 2-fold higher in the high Mg group than in the low Mg group. CONCLUSIONS Hypomagnesemia from 1 to 12 months after renal transplantation is associated with a better allograft function up to 5 years posttransplant. This relationship was found to hold true after accounting for baseline allograft function and the presence of slow graft function.
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Affiliation(s)
- Tammy Hod
- Sheba Medical Center, Nephrology Department, Tel Aviv University, Tel Aviv, Israel,
| | - Ofer Isakov
- Department of Internal Medicine "T", Tel Aviv Souraski Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Bhanu K Patibandla
- Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon, USA
| | - Kenneth B Christopher
- Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Rami Hershkoviz
- Department of Internal Medicine "T", Tel Aviv Souraski Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Idit F Schwartz
- Department of Internal Medicine "T", Tel Aviv Souraski Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Anil Chandraker
- Transplant Research Center, Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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van Rijn MHC, van de Luijtgaarden M, van Zuilen AD, Blankestijn PJ, Wetzels JFM, Debray TPA, van den Brand JAJG. Prognostic models for chronic kidney disease: a systematic review and external validation. Nephrol Dial Transplant 2020; 36:1837-1850. [PMID: 33051669 DOI: 10.1093/ndt/gfaa155] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Accurate risk prediction is needed in order to provide personalized healthcare for chronic kidney disease (CKD) patients. An overload of prognosis studies is being published, ranging from individual biomarker studies to full prediction studies. We aim to systematically appraise published prognosis studies investigating multiple biomarkers and their role in risk predictions. Our primary objective was to investigate if the prognostic models that are reported in the literature were of sufficient quality and to externally validate them. METHODS We undertook a systematic review and appraised the quality of studies reporting multivariable prognosis models for end-stage renal disease (ESRD), cardiovascular (CV) events and mortality in CKD patients. We subsequently externally validated these models in a randomized trial that included patients from a broad CKD population. RESULTS We identified 91 papers describing 36 multivariable models for prognosis of ESRD, 50 for CV events, 46 for mortality and 17 for a composite outcome. Most studies were deemed of moderate quality. Moreover, they often adopted different definitions for the primary outcome and rarely reported full model equations (21% of the included studies). External validation was performed in the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners trial (n = 788, with 160 events for ESRD, 79 for CV and 102 for mortality). The 24 models that reported full model equations showed a great variability in their performance, although calibration remained fairly adequate for most models, except when predicting mortality (calibration slope >1.5). CONCLUSIONS This review shows that there is an abundance of multivariable prognosis models for the CKD population. Most studies were considered of moderate quality, and they were reported and analysed in such a manner that their results cannot directly be used in follow-up research or in clinical practice.
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Affiliation(s)
- Marieke H C van Rijn
- Department of Nephrology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Moniek van de Luijtgaarden
- Department of Nephrology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Arjan D van Zuilen
- Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Peter J Blankestijn
- Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jack F M Wetzels
- Department of Nephrology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Thomas P A Debray
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Jan A J G van den Brand
- Department of Nephrology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
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40
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Carrero JJ, González-Ortiz A, Avesani CM, Bakker SJL, Bellizzi V, Chauveau P, Clase CM, Cupisti A, Espinosa-Cuevas A, Molina P, Moreau K, Piccoli GB, Post A, Sezer S, Fouque D. Plant-based diets to manage the risks and complications of chronic kidney disease. Nat Rev Nephrol 2020; 16:525-542. [PMID: 32528189 DOI: 10.1038/s41581-020-0297-2] [Citation(s) in RCA: 175] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/23/2020] [Indexed: 02/07/2023]
Abstract
Traditional dietary recommendations for patients with chronic kidney disease (CKD) focus on the quantity of nutrients consumed. Without appropriate dietary counselling, these restrictions can result in a low intake of fruits and vegetables and a lack of diversity in the diet. Plant nutrients and plant-based diets could have beneficial effects in patients with CKD: increased fibre intake shifts the gut microbiota towards reduced production of uraemic toxins; plant fats, particularly olive oil, have anti-atherogenic effects; plant anions might mitigate metabolic acidosis and slow CKD progression; and as plant phosphorus has a lower bioavailability than animal phosphorus, plant-based diets might enable better control of hyperphosphataemia. Current evidence suggests that promoting the adoption of plant-based diets has few risks but potential benefits for the primary prevention of CKD, as well as for delaying progression in patients with CKD G3-5. These diets might also help to manage and prevent some of the symptoms and metabolic complications of CKD. We suggest that restriction of plant foods as a strategy to prevent hyperkalaemia or undernutrition should be individualized to avoid depriving patients with CKD of these potential beneficial effects of plant-based diets. However, research is needed to address knowledge gaps, particularly regarding the relevance and extent of diet-induced hyperkalaemia in patients undergoing dialysis.
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Affiliation(s)
- Juan J Carrero
- Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
| | - Ailema González-Ortiz
- Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Nephrology and Mineral Metabolism Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador, Zubirán, Mexico
| | - Carla M Avesani
- Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Stephan J L Bakker
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Vincenzo Bellizzi
- Nephrology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy
| | - Philippe Chauveau
- Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux et Aurad-Aquitaine, Bordeaux, France
| | - Catherine M Clase
- Departments of Medicine and Health Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Adamasco Cupisti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Angeles Espinosa-Cuevas
- Nephrology and Mineral Metabolism Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador, Zubirán, Mexico
| | - Pablo Molina
- Department of Nephrology, Hospital Universitari Dr Peset, Universitat de València, València, Spain
| | - Karine Moreau
- Renal transplant unit, Pellegrin Hospital, Bordeaux, France
| | - Giorgina B Piccoli
- Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.,Nephrologie, Centre Hospitalier Le Mans, Le Mans, France
| | - Adrian Post
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Siren Sezer
- Department of Nephrology, Baskent University School of Medicine, Ankara, Turkey
| | - Denis Fouque
- Department of Nephrology, Université de Lyon, Carmen, Hospital Lyon-Sud, Lyon, France
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Azem R, Daou R, Bassil E, Anvari EM, Taliercio JJ, Arrigain S, Schold JD, Vachharajani T, Nally J, Na Khoul GN. Serum magnesium, mortality and disease progression in chronic kidney disease. BMC Nephrol 2020; 21:49. [PMID: 32050924 PMCID: PMC7017617 DOI: 10.1186/s12882-020-1713-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 02/06/2020] [Indexed: 11/10/2022] Open
Abstract
Introduction Magnesium disorders are commonly encountered in chronic kidney disease (CKD) and are typically a consequence of decreased kidney function or frequently prescribed medications such as diuretics and proton pump inhibitors. While hypomagnesemia has been linked with increased mortality, the association between elevated magnesium levels and mortality is not clearly defined. Additionally, associations between magnesium disorders, type of death, and CKD progression have not been reported. Therefore, we studied the associations between magnesium levels, CKD progression, mortality, and cause specific deaths in patients with CKD. Methods Using the Cleveland Clinic CKD registry, we identified 10,568 patients with estimated Glomerular Filtration Rate (eGFR) between 15 and 59 ml/min/1.73 m2 in this range for a minimum of 3 months with a measured magnesium level. We categorized subjects into 3 groups based on these magnesium levels (≤ 1.7, 1.7–2.6 and > 2.6 mg/dl) and applied cox regression modeling and competing risk models to identify associations with overall and cause-specific mortality. We also evaluated the association between magnesium level and slope of eGFR using mixed models. Results During a median follow-up of 3.7 years, 4656 (44%) patients died. After adjusting for relevant covariates, a magnesium level < 1.7 mg/dl (vs. 1.7–2.6 mg/dl) was associated with higher overall mortality (HR = 1.14, 95% CI: 1.04, 1.24), and with higher sub-distribution hazards for non-cardiovascular non-malignancy mortality (HR = 1.29, 95% CI: 1.12, 1.49). Magnesium levels > 2.6 mg/dl (vs. 1.7–2.6 mg/dl) was associated with a higher risk of all-cause death only (HR = 1.23, 95% CI: 1.03, 1.48). We found similar results when evaluating magnesium as a continuous measure. There were no significant differences in the slope of eGFR across all three magnesium groups (p = 0.10). Conclusions In patients with CKD stage 3 and 4, hypomagnesemia was associated with higher all-cause and non-cardiovascular non-malignancy mortality. Hypermagnesemia was associated with higher all-cause mortality. Neither hypo nor hypermagnesemia were associated with an increased risk of CKD progression.
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Affiliation(s)
- Rami Azem
- Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue - Q7, Cleveland, OH, 44195, USA
| | - Remy Daou
- Department of Family Medicine, Saint Joseph University, Beirut, Lebanon
| | - Elias Bassil
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Eva Maria Anvari
- Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue - Q7, Cleveland, OH, 44195, USA.,Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Jonathan J Taliercio
- Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue - Q7, Cleveland, OH, 44195, USA.,Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Susana Arrigain
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - Jesse D Schold
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - Tushar Vachharajani
- Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue - Q7, Cleveland, OH, 44195, USA.,Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Joseph Nally
- Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue - Q7, Cleveland, OH, 44195, USA.,Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Georges N Na Khoul
- Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue - Q7, Cleveland, OH, 44195, USA. .,Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
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Pendón-Ruiz de Mier MV, Rodelo-Haad C, Díaz-Tocados JM, Muñoz-Castañeda JR, Rodríguez M. Magnesium: An old player revisited in the context of CKD-MBD. Clin Chim Acta 2019; 501:53-59. [PMID: 31836501 DOI: 10.1016/j.cca.2019.11.037] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 11/27/2019] [Accepted: 11/27/2019] [Indexed: 12/18/2022]
Abstract
Chronic kidney disease (CKD) is associated with a wide number of abnormalities in mineral metabolism. Often, these alterations are the leading players in the development of comorbidities associated with CKD, which are risk factors of mortality. In this context, mineral and bone disorder associated with CKD (CKD-MBD) are highlighted, connecting bone, renal, and cardiovascular disorders. Many studies have been led to propose strategies to avoid, reduce, or slow down CKD-MBD progression using different compositions of metallic elements-based P binders such as aluminum, magnesium, or calcium. Magnesium, the aim of this review, has been used by nephrologists to treat CKD-MBD with a variable acceptation due mainly to different results on bone homeostasis. Nowadays, we have new evidence about the efficacy of magnesium supplementation on vascular calcification, renal function, and bone disorders, suggesting potential beneficial effects of Magnesium in the management of CKD-MBD.
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Affiliation(s)
- M V Pendón-Ruiz de Mier
- Maimonides Institute for Biomedical Research (IMIBIC), Cordoba, Spain; University of Cordoba, Spain; Nephrology Service, Reina Sofia University Hospital, Cordoba, Spain; Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain
| | - C Rodelo-Haad
- Maimonides Institute for Biomedical Research (IMIBIC), Cordoba, Spain; University of Cordoba, Spain; Nephrology Service, Reina Sofia University Hospital, Cordoba, Spain; Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain
| | - J M Díaz-Tocados
- Maimonides Institute for Biomedical Research (IMIBIC), Cordoba, Spain; University of Cordoba, Spain
| | - J R Muñoz-Castañeda
- Maimonides Institute for Biomedical Research (IMIBIC), Cordoba, Spain; University of Cordoba, Spain; Nephrology Service, Reina Sofia University Hospital, Cordoba, Spain; Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain.
| | - M Rodríguez
- Maimonides Institute for Biomedical Research (IMIBIC), Cordoba, Spain; University of Cordoba, Spain; Nephrology Service, Reina Sofia University Hospital, Cordoba, Spain; Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain
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43
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Chacar FC, Kogika MM, Ferreira AC, Kanayama KK, Reche A. Total serum magnesium in cats with chronic kidney disease with nephrolithiasis. J Feline Med Surg 2019; 21:1172-1180. [PMID: 30694098 PMCID: PMC10814274 DOI: 10.1177/1098612x18823588] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVES Magnesium has been 'the forgotten ion' for many years. Over the past decade, however, the role of magnesium in essential physiological functions and several illness conditions have been elucidated. Nevertheless, the investigation of magnesium in cats with chronic kidney disease (CKD) and nephrolithiasis is yet to be determined. The purpose of this study was to investigate whether CKD cats with nephrolithiasis have changes in total serum magnesium concentrations, and whether magnesium disorders may be associated with other electrolyte disturbances, as well as with prognosis. We also aimed to evaluate whether total serum magnesium concentration differs between CKD cats with and without nephrolithiasis. METHODS Total serum magnesium concentrations were assessed in 42 cats with CKD with stage 1-4 nephrolithiasis. The correlation between magnesium and other electrolytes, as well as Kaplan-Meier survival analysis, were performed. We also selected 14 control cats with CKD without nephrolithiasis age-matched with 14 cats with CKD with nephrolithiasis. RESULTS Hypermagnesemia was observed in 16/42 (38.1%) and hypomagnesemia in 6/42 (14.3%) cats. Serum magnesium abnormalities were observed in cats of all stages, and marked hypermagnesemia was noted in cats with stage 4 CKD with nephrolithiasis (P <0.001). There was a negative correlation between total serum magnesium and ionized calcium (r = -0.64; P <0.01), and a positive correlation between total serum magnesium and serum phosphorus (r = 0.58, P = 0.01). Cats with CKD with nephrolithiasis and hypomagnesemia or hypermagnesemia had higher mortality than those with normal total serum magnesium concentration (P <0.01), regardless of CKD stage. There was no difference in total serum magnesium concentration between CKD cats with and without nephrolithiasis. CONCLUSIONS AND RELEVANCE Cats with CKD with nephrolithiasis have magnesium abnormalities. Hypomagnesemia and hypermagnesemia were associated with an increase in mortality, and thus total serum magnesium abnormalities may be used as prognostic factors in these cases.
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Affiliation(s)
- Fernanda Chicharo Chacar
- Internal Medicine, School of Veterinary Medicine and Animal Science/University of Sao Paulo, Sao Paulo, Brazil
| | - Marcia Mery Kogika
- Internal Medicine, School of Veterinary Medicine and Animal Science/University of Sao Paulo, Sao Paulo, Brazil
| | - Andréa C Ferreira
- Internal Medicine, School of Veterinary Medicine and Animal Science/University of Sao Paulo, Sao Paulo, Brazil
| | - Khadine K Kanayama
- Internal Medicine, School of Veterinary Medicine and Animal Science/University of Sao Paulo, Sao Paulo, Brazil
| | - Archivaldo Reche
- Internal Medicine, School of Veterinary Medicine and Animal Science/University of Sao Paulo, Sao Paulo, Brazil
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44
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Disthabanchong S, Srisuwarn P. Mechanisms of Vascular Calcification in Kidney Disease. Adv Chronic Kidney Dis 2019; 26:417-426. [PMID: 31831120 DOI: 10.1053/j.ackd.2019.08.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 08/18/2019] [Accepted: 08/19/2019] [Indexed: 02/07/2023]
Abstract
The increase in prevalence and severity of vascular calcification in chronic kidney disease is a result of complex interactions between changes in the vascular bed, mineral metabolites, and other uremic factors. Vascular calcification can occur in the intima and the media of arterial wall. Under permissive conditions, vascular smooth muscle cells (VSMCs) can transform to osteoblast-like phenotype. The membrane-bound vesicles released from transformed VSMCs and the apoptotic bodies derived from dying VSMCs serve as nucleating structures for calcium crystal formation. Alterations in the quality and the quantity of endogenous calcification inhibitors also give rise to an environment that potentiates calcification.
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Affiliation(s)
- Sinee Disthabanchong
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
| | - Praopilad Srisuwarn
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Grant CH, Gillis KA, Lees JS, Traynor JP, Mark PB, Stevens KI. Proton pump inhibitor use and progression to major adverse renal events: a competing risk analysis. QJM 2019; 112:835-840. [PMID: 31251364 DOI: 10.1093/qjmed/hcz166] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are associated with acute tubulointerstitial nephritis and there are reports associating their use with the development of chronic kidney disease (CKD). AIM To determine if PPI use is associated with major adverse renal events (MARE) in patients with CKD. DESIGN Observational cohort study comprising patients with CKD attending secondary care renal clinics from 1 January 2006 until 31 December 2016. METHODS We collated baseline clinical, socio-demographic and biochemical data at start of PPI (PPI group) or study inception (control group). MARE was considered a composite of doubling of creatinine or end-stage renal disease. Association between PPI exposure and progression to MARE was assessed by cause-specific hazards competing risk survival analysis. RESULTS There were 3824 patients with CKD included in the analyses of whom 1195 were prescribed a PPI. The PPI group was younger (64.8 vs. 67.0 years, P < 0.001), with lower estimated glomerular filtration rate (eGFR) (30 vs. 35 ml/min, P < 0.001) and more proteinuria (64 vs. 48 mg/mmol, P < 0.001). PPI use was associated with progression to MARE on multivariable adjustment (hazard ratio 1.13 [95% confidence interval 1.02-1.25], P = 0.021). Other factors significantly associated with progression to MARE were higher systolic blood pressure, lower eGFR, greater proteinuria, congestive cardiac failure and diabetes. Hypomagnesaemia was more common in the PPI group (39.5 vs. 18.9%, P < 0.001). CONCLUSION PPI use was associated with progression to MARE, but not death in patients with CKD after adjusting for factors known to predict declining renal function, including lower eGFR, proteinuria and comorbidities. A prospective cohort study is required to validate these findings.
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Affiliation(s)
- C H Grant
- From the School of Medicine, College of Medical, Veterinary & Life Sciences, University Avenue, The University of Glasgow, Glasgow G12 8QQ, UK
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow G51 4TF, UK
| | - K A Gillis
- From the School of Medicine, College of Medical, Veterinary & Life Sciences, University Avenue, The University of Glasgow, Glasgow G12 8QQ, UK
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow G51 4TF, UK
| | - J S Lees
- From the School of Medicine, College of Medical, Veterinary & Life Sciences, University Avenue, The University of Glasgow, Glasgow G12 8QQ, UK
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow G51 4TF, UK
| | - J P Traynor
- From the School of Medicine, College of Medical, Veterinary & Life Sciences, University Avenue, The University of Glasgow, Glasgow G12 8QQ, UK
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow G51 4TF, UK
| | - P B Mark
- From the School of Medicine, College of Medical, Veterinary & Life Sciences, University Avenue, The University of Glasgow, Glasgow G12 8QQ, UK
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow G51 4TF, UK
| | - K I Stevens
- From the School of Medicine, College of Medical, Veterinary & Life Sciences, University Avenue, The University of Glasgow, Glasgow G12 8QQ, UK
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow G51 4TF, UK
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Ferdaus MZ, Mukherjee A, Nelson JW, Blatt PJ, Miller LN, Terker AS, Staub O, Lin DH, McCormick JA. Mg 2+ restriction downregulates NCC through NEDD4-2 and prevents its activation by hypokalemia. Am J Physiol Renal Physiol 2019; 317:F825-F838. [PMID: 31364380 PMCID: PMC6843039 DOI: 10.1152/ajprenal.00216.2019] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Hypomagnesemia is associated with reduced kidney function and life-threatening complications and sustains hypokalemia. The distal convoluted tubule (DCT) determines final urinary Mg2+ excretion and, via activity of the Na+-Cl- cotransporter (NCC), also plays a key role in K+ homeostasis by metering Na+ delivery to distal segments. Little is known about the mechanisms by which plasma Mg2+ concentration regulates NCC activity and how low-plasma Mg2+ concentration and K+ concentration interact to modulate NCC activity. To address this, we performed dietary manipulation studies in mice. Compared with normal diet, abundances of total NCC and phosphorylated NCC (pNCC) were lower after short-term (3 days) or long-term (14 days) dietary Mg2+ restriction. Altered NCC activation is unlikely to play a role, since we also observed lower total NCC abundance in mice lacking the two NCC-activating kinases, STE20/SPS-1-related proline/alanine-rich kinase and oxidative stress response kinase-1, after Mg2+ restriction. The E3 ubiquitin-protein ligase NEDD4-2 regulates NCC abundance during dietary NaCl loading or K+ restriction. Mg2+ restriction did not lower total NCC abundance in inducible nephron-specific neuronal precursor cell developmentally downregulated 4-2 (NEDD4-2) knockout mice. Total NCC and pNCC abundances were similar after short-term Mg2+ or combined Mg2+-K+ restriction but were dramatically lower compared with a low-K+ diet. Therefore, sustained NCC downregulation may serve a mechanism that enhances distal Na+ delivery during states of hypomagnesemia, maintaining hypokalemia. Similar results were obtained with long-term Mg2+-K+ restriction, but, surprisingly, NCC was not activated after long-term K+ restriction despite lower plasma K+ concentration, suggesting significant differences in distal tubule adaptation to acute or chronic K+ restriction.
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Affiliation(s)
- Mohammed Z. Ferdaus
- 1Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon
| | - Anindit Mukherjee
- 1Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon
| | - Jonathan W. Nelson
- 1Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon
| | - Philip J. Blatt
- 1Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon
| | - Lauren N. Miller
- 1Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon
| | - Andrew S. Terker
- 2Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Olivier Staub
- 3Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland
| | - Dao-Hong Lin
- 4Department of Pharmacology, New York Medical College, Valhalla, New York
| | - James A. McCormick
- 1Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon
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Ferrè S, Li X, Adams-Huet B, Maalouf NM, Sakhaee K, Toto RD, Moe OW, Neyra JA. Association of serum magnesium with all-cause mortality in patients with and without chronic kidney disease in the Dallas Heart Study. Nephrol Dial Transplant 2019; 33:1389-1396. [PMID: 29077944 DOI: 10.1093/ndt/gfx275] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 08/08/2017] [Indexed: 01/08/2023] Open
Abstract
Background Low serum magnesium (SMg) has been linked to increased mortality and cardiovascular disease (CVD) in the general population. We examined whether this association is similar in participants with versus without prevalent chronic kidney disease (CKD) in the multiethnic Dallas Heart Study (DHS) cohort. Methods SMg was analyzed as a continuous variable and divided into tertiles. Study outcomes were all-cause death, cardiovascular (CV) death or event, and CVD surrogate markers, evaluated using multivariable Cox regression models adjusted for demographics, comorbidity, anthropometric and biochemical parameters including albumin, phosphorus and parathyroid hormone, and diuretic use. Median follow-up was 12.3 years (11.9-12.8, 25th percentile-75th percentile). Results Among 3551 participants, 306 (8.6%) had prevalent CKD. Mean SMg was 2.08 ± 0.19 mg/dL (0.85 ± 0.08 mM, mean ± SD) in the CKD and 2.07 ± 0.18 mg/dL (0.85 ± 0.07 mM) in the non-CKD subgroups. During the follow-up period, 329 all-cause deaths and 306 CV deaths or events occurred. In a fully adjusted model, every 0.2 mg/dL decrease in SMg was associated with ∼20-40% increased hazard for all-cause death in both CKD and non-CKD subgroups. In CKD participants, the lowest SMg tertile was also independently associated with all-cause death (adjusted hazard ratio 2.31; 95% confidence interval 1.23-4.36 versus 1.15; 0.55-2.41; for low versus high tertile, respectively). Conclusions Low SMg levels (1.4-1.9 mg/dL; 0.58-0.78 mM) were independently associated with all-cause death in patients with prevalent CKD in the DHS cohort. Randomized clinical trials are important to determine whether Mg supplementation affects survival in CKD patients.
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Affiliation(s)
- Silvia Ferrè
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Division of Mineral Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Xilong Li
- Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Beverley Adams-Huet
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Division of Mineral Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Naim M Maalouf
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Division of Mineral Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Khashayar Sakhaee
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Division of Mineral Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Robert D Toto
- Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Orson W Moe
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Division of Mineral Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Javier A Neyra
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky, Lexington, KY, USA
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Cases A, Cigarrán-Guldrís S, Mas S, Gonzalez-Parra E. Vegetable-Based Diets for Chronic Kidney Disease? It Is Time to Reconsider. Nutrients 2019; 11:E1263. [PMID: 31167346 PMCID: PMC6627351 DOI: 10.3390/nu11061263] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 05/23/2019] [Accepted: 05/30/2019] [Indexed: 12/12/2022] Open
Abstract
Traditional dietary recommendations to renal patients limited the intake of fruits and vegetables because of their high potassium content. However, this paradigm is rapidly changing due to the multiple benefits derived from a fundamentally vegetarian diet such as, improvement in gut dysbiosis, reducing the number of pathobionts and protein-fermenting species leading to a decreased production of the most harmful uremic toxins, while the high fiber content of these diets enhances intestinal motility and short-chain fatty acid production. Metabolic acidosis in chronic kidney disease (CKD) is aggravated by the high consumption of meat and refined cereals, increasing the dietary acid load, while the intake of fruit and vegetables is able to neutralize the acidosis and its deleterious consequences. Phosphorus absorption and bioavailability is also lower in a vegetarian diet, reducing hyperphosphatemia, a known cause of cardiovascular mortality in CKD. The richness of multiple plants in magnesium and vitamin K avoids their deficiency, which is common in these patients. These beneficial effects, together with the reduction of inflammation and oxidative stress observed with these diets, may explain the reduction in renal patients' complications and mortality, and may slow CKD progression. Finally, although hyperkalemia is the main concern of these diets, the use of adequate cooking techniques can minimize the amount absorbed.
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Affiliation(s)
- Aleix Cases
- Medicine Department, Universitat de Barcelona, Institut d'Investigacions Biomèqiques August Pi i Sunyer, 08036 Barcelona, Spain.
| | | | - Sebastián Mas
- Servicio de Nefrología, Fundación Jiménez Díaz, 28040 Madrid, Spain.
- Centro de investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain.
| | - Emilio Gonzalez-Parra
- Servicio de Nefrología, Fundación Jiménez Díaz, 28040 Madrid, Spain.
- Red de Investigación Renal (RedinRen), 28029 Madrid, Spain.
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Wu L, Cai K, Luo Q, Wang L, Hong Y. Baseline Serum Magnesium Level and Its Variability in Maintenance Hemodialysis Patients: Associations with Mortality. Kidney Blood Press Res 2019; 44:222-232. [PMID: 30921805 DOI: 10.1159/000498957] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 01/04/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS The study aimed at investigating the impact of serum magnesium (Mg) baseline level and its variability on mortality in maintenance hemodialysis (MHD) patients. METHODS Eligible patients receiving regular MHD at Ningbo No. 2 Hospital between January 2009 and August 2016 were enrolled and follow-ups were conducted afterwards until death or transplantation. General information, laboratory results, and outcomes of subjects were collected. The relationship between baseline serum Mg level, its coefficient of variation (CV), and all-cause mortality and cardiovascular disease mortality were assessed, respectively. Subjects were divided into groups in 2 manners: by serum Mg level (lower Mg group: serum Mg <1.00 mmol/L, higher Mg group: serum Mg ≥1.00 mmol/L) and by serum Mg CV (high variation group: CV ≥0.149 mmol/L, middle variation group: 0.114 mmol/L ≤ CV < 0.149 mmol/L, and low variation group: CV <0.114 mmol/L). RESULTS 169 MHD patients were recruited in the study, with mean serum Mg 1.00 ± 0.18 mmol/L, average age 60.20 ± 15.64 years, and median dialysis duration 37.00 (18.30, 77.97) months. During the follow-up, 69 (40.83%) patients died, 24 (34.78%) of which died due to cardiovascular disease. Comparing the two groups, patients in the lower Mg group had a higher all-cause mortality (50.00 vs. 29.33%, p = 0.007). The multivariate Cox regression analysis suggested that lower Mg level was an independent factor for all-cause mortality as well as cardiovascular mortality (HR = 13.268, 95% CI 6.234-28.237, p < 0.001; HR = 12.702, 95% CI 3.737-43.174, p < 0.001, respectively). However, there were no significant statistical differences of all-cause and cardiovascular mortality among these three groups concerning Mg variation. And in the univariate and multivariate Cox regression analysis, serum magnesium CV was not the independent factor for all-cause mortality and cardiovascular mortality. CONCLUSIONS The lower baseline serum magnesium level was associated with all-cause and cardiovascular mortality in MHD patients. However, the variability of magnesium level was not independently associated with the risk of death and further studies need to be conducted.
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Affiliation(s)
- Lingping Wu
- Department of Nephrology, Ningbo No. 2 Hospital, School of Medicine, Ningbo University, Ningbo, China
| | - Kedan Cai
- Department of Nephrology, Ningbo No. 2 Hospital, School of Medicine, Ningbo University, Ningbo, China
| | - Qun Luo
- Department of Nephrology, Ningbo No. 2 Hospital, School of Medicine, Ningbo University, Ningbo, China,
| | - Lailiang Wang
- Department of Nephrology, Ningbo No. 2 Hospital, School of Medicine, Ningbo University, Ningbo, China
| | - Yue Hong
- Department of Nephrology, Ningbo No. 2 Hospital, School of Medicine, Ningbo University, Ningbo, China
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Xiong J, He T, Wang M, Nie L, Zhang Y, Wang Y, Huang Y, Feng B, Zhang J, Zhao J. Serum magnesium, mortality, and cardiovascular disease in chronic kidney disease and end-stage renal disease patients: a systematic review and meta-analysis. J Nephrol 2019; 32:791-802. [PMID: 30888644 DOI: 10.1007/s40620-019-00601-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 03/16/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Previous studies reported that magnesium deficiency was associated with vascular calcifications, atherosclerosis and cardiovascular disease, which might play an independent pathogenic role in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. However, the results of these studies were somewhat underpowered and inconclusive. METHODS Literature was identified by searching PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL). We included studies that investigated the association between serum magnesium with mortality risk in CKD and ESRD patients. Unadjusted and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled. RESULTS Twenty studies involving 200,934 participants were included, and the results showed that there was a strong association between hypomagnesemia and the risk of all-cause mortality in patients with CKD and ESRD (HR 1.32; 95% CI 1.19-1.47; p < 0.00001) (hypomagnesemia vs. normal magnesium or hypermagnesemia) after multivariable adjusted. On the contrary, hypermagnesemia was inversely associated with all-cause mortality in patients with CKD and ESRD (HR 0.86; 95% CI 0.79-0.94; p = 0.001) (per unit increase). Moreover, a significant association between hypermagnesemia and decreased risk of cardiovascular mortality was observed (HR 0.71; 95% CI 053-0.97, p = 0.03) in the adjusted model. In addition, subgroup analysis found that hypomagnesemia was strongly associated with increased all-cause mortality in hemodialysis patients (HR 1.29; 95% CI 1.12-1.50; p = 0.0005) (hypomagnesemia vs. normal magnesium or hypermagnesemia). CONCLUSIONS Our results indicate that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in patients with CKD and ESRD. Further studies evaluating benefits of magnesium correction in CKD and dialysis patients with hypomagnesemia should be performed.
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Affiliation(s)
- Jiachuan Xiong
- Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
| | - Ting He
- Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
| | - Min Wang
- Department of Otorhinolaryngology and Head-Neck Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
| | - Ling Nie
- Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
| | - Ying Zhang
- Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
| | - Yiqin Wang
- Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
| | - Yunjian Huang
- Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
| | - Bing Feng
- Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
| | - Jingbo Zhang
- Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
| | - Jinghong Zhao
- Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.
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