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Magagnoli L, Cozzolino M, Caskey FJ, Evans M, Torino C, Porto G, Szymczak M, Krajewska M, Drechsler C, Stenvinkel P, Pippias M, Dekker FW, de Rooij ENM, Wanner C, Chesnaye NC, Jager KJ. Association between CKD-MBD and mortality in older patients with advanced CKD-results from the EQUAL study. Nephrol Dial Transplant 2023; 38:2562-2575. [PMID: 37230954 PMCID: PMC10615632 DOI: 10.1093/ndt/gfad100] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication of CKD; it is associated with higher mortality in dialysis patients, while its impact in non-dialysis patients remains mostly unknown. We investigated the associations between parathyroid hormone (PTH), phosphate and calcium (and their interactions), and all-cause, cardiovascular (CV) and non-CV mortality in older non-dialysis patients with advanced CKD. METHODS We used data from the European Quality study, which includes patients aged ≥65 years with estimated glomerular filtration rate ≤20 mL/min/1.73 m2 from six European countries. Sequentially adjusted Cox models were used to assess the association between baseline and time-dependent CKD-MBD biomarkers and all-cause, CV and non-CV mortality. Effect modification between biomarkers was also assessed. RESULTS In 1294 patients, the prevalence of CKD-MBD at baseline was 94%. Both PTH [adjusted hazard ratio (aHR) 1.12, 95% confidence interval (CI) 1.03-1.23, P = .01] and phosphate (aHR 1.35, 95% CI 1.00-1.84, P = .05), but not calcium (aHR 1.11, 95% CI 0.57-2.17, P = .76), were associated with all-cause mortality. Calcium was not independently associated with mortality, but modified the effect of phosphate, with the highest mortality risk found in patients with both hypercalcemia and hyperphosphatemia. PTH level was associated with CV mortality, but not with non-CV mortality, whereas phosphate was associated with both CV and non-CV mortality in most models. CONCLUSIONS CKD-MBD is very common in older non-dialysis patients with advanced CKD. PTH and phosphate are independently associated with all-cause mortality in this population. While PTH level is only associated with CV mortality, phosphate seems to be associated with both CV and non-CV mortality.
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Affiliation(s)
- Lorenza Magagnoli
- University of Milan, Department of Health Sciences, Milan, Italy
- ASST Santi Paolo e Carlo, Renal Division, Milan, Italy
| | - Mario Cozzolino
- University of Milan, Department of Health Sciences, Milan, Italy
- ASST Santi Paolo e Carlo, Renal Division, Milan, Italy
| | - Fergus J Caskey
- University of Bristol, Population Health Sciences, Bristol, UK
- North Bristol NHS Trust, Renal Unit, Bristol, UK
| | - Marie Evans
- Karolinska Institutet, Department of Clinical Intervention and Technology (CLINTEC), Stockholm, Sweden
| | - Claudia Torino
- Istituto di Fisiologia Clinica Consiglio Nazionale delle Ricerche (IFC-CNR), Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (IT)
| | - Gaetana Porto
- G.O.M., Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Maciej Szymczak
- Wroclaw Medical University, Department of Nephrology and Transplantation Medicine, Wroclaw, Poland
| | - Magdalena Krajewska
- Wroclaw Medical University, Department of Nephrology and Transplantation Medicine, Wroclaw, Poland
| | | | - Peter Stenvinkel
- Karolinska Institutet, Department of Clinical Intervention and Technology (CLINTEC), Stockholm, Sweden
| | - Maria Pippias
- University of Bristol, Population Health Sciences, Bristol, UK
- North Bristol NHS Trust, Renal Unit, Bristol, UK
| | - Friedo W Dekker
- Leiden University Medical Center, Department of Clinical Epidemiology, Leiden, The Netherlands
| | - Esther N M de Rooij
- Leiden University Medical Center, Department of Clinical Epidemiology, Leiden, The Netherlands
| | - Christoph Wanner
- University Hospital Würzburg, Division of Nephrology, Würzburg, Germany
| | - Nicholas C Chesnaye
- Amsterdam UMC location AMC, Medical Informatics, ERA Registry, Amsterdam, The Netherlands
- Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, The Netherlands
| | - Kitty J Jager
- Amsterdam UMC location AMC, Medical Informatics, ERA Registry, Amsterdam, The Netherlands
- Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, The Netherlands
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Macdougall IC, Ponikowski P, Stack AG, Wheeler DC, Anker SD, Butler J, Filippatos G, Göhring UM, Kirwan BA, Kumpeson V, Metra M, Rosano G, Ruschitzka F, van der Meer P, Wächter S, Jankowska EA. Ferric Carboxymaltose in Iron-Deficient Patients with Hospitalized Heart Failure and Reduced Kidney Function. Clin J Am Soc Nephrol 2023; 18:1124-1134. [PMID: 37382961 PMCID: PMC10564367 DOI: 10.2215/cjn.0000000000000223] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 06/23/2023] [Indexed: 06/30/2023]
Abstract
BACKGROUND Reduced kidney function is common among patients with heart failure. In patients with heart failure and/or kidney disease, iron deficiency is an independent predictor of adverse outcomes. In the AFFIRM-AHF trial, patients with acute heart failure with iron deficiency treated with intravenous ferric carboxymaltose demonstrated reduced risk of heart failure hospitalization, with improved quality of life. We aimed to further characterize the impact of ferric carboxymaltose among patients with coexisting kidney impairment. METHODS The double-blind, placebo-controlled AFFIRM-AHF trial randomized 1132 stabilized adults with acute heart failure (left ventricular ejection fraction <50%) and iron deficiency. Patients on dialysis were excluded. The primary end point was a composite of total heart failure hospitalizations and cardiovascular death during the 52-week follow-up period. Additional end points included cardiovascular hospitalizations, total heart failure hospitalizations, and days lost to heart failure hospitalizations or cardiovascular death. For this subgroup analysis, patients were stratified according to baseline eGFR. RESULTS Overall, 60% of patients had an eGFR <60 ml/min per 1.73 m 2 (the lower eGFR subgroup). These patients were significantly older, more likely to be female and to have ischemic heart failure, and had higher baseline serum phosphate levels and higher rates of anemia. For all end points, event rates were higher in the lower eGFR group. In the lower eGFR group, the annualized event rates for the primary composite outcome were 68.96 and 86.30 per 100 patient-years in the ferric carboxymaltose and placebo arms, respectively (rate ratio, 0.76; 95% confidence interval, 0.54 to 1.06). The treatment effect was similar in the higher eGFR subgroup (rate ratio, 0.65; 95% confidence interval, 0.42 to 1.02; Pinteraction = 0.60). A similar pattern was observed for all end points ( Pinteraction > 0.05). CONCLUSIONS In a cohort of patients with acute heart failure, left ventricular ejection fraction <50%, and iron deficiency, the safety and efficacy of ferric carboxymaltose were consistent across a range of eGFR values. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency (Affirm-AHF), NCT02937454 .
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Affiliation(s)
- Iain C. Macdougall
- Department of Renal Medicine, King's College Hospital, London, United Kingdom
| | - Piotr Ponikowski
- Institute of Heart Diseases, Wrocław Medical University, and Institute of Heart Diseases, University Hospital, Wrocław, Poland
| | - Austin G. Stack
- Department of Nephrology, University Hospital Limerick and School of Medicine, University of Limerick, Limerick, Ireland
| | - David C. Wheeler
- Department of Renal Medicine, University College London, London, United Kingdom
| | - Stefan D. Anker
- Department of Cardiology, Charité, Campus Virchow-Klinikum, Berlin, Germany
| | - Javed Butler
- Department of Medicine, Baylor University Medical Center, Dallas, Texas
- Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Gerasimos Filippatos
- Department of Cardiology, National and Kapodistrian University of Athens School of Medicine, Athens University, Athens, Greece
| | | | - Bridget-Anne Kirwan
- Department of Clinical Research, SOCAR Research SA, Nyon, Switzerland
- London School of Hygiene and Tropical Medicine, University College London, London, United Kingdom
| | | | - Marco Metra
- Department of Cardiology, University and Civil Hospital, Brescia, Italy
| | - Giuseppe Rosano
- Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy
| | - Frank Ruschitzka
- Department of Cardiology, University Heart Center, University Hospital Zürich and University of Zürich, Zürich, Switzerland
| | - Peter van der Meer
- University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands
| | | | - Ewa A. Jankowska
- Institute of Heart Diseases, Wrocław Medical University, and Institute of Heart Diseases, University Hospital, Wrocław, Poland
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Rosano GMC, Kalantar‐Zadeh K, Jankowska EA. Hypophosphataemia risk associated with ferric carboxymaltose in heart failure: A pooled analysis of clinical trials. ESC Heart Fail 2023; 10:1294-1304. [PMID: 36722321 PMCID: PMC10053364 DOI: 10.1002/ehf2.14286] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 11/30/2022] [Accepted: 01/09/2023] [Indexed: 02/02/2023] Open
Abstract
AIMS Iron deficiency is a common finding among patients with heart failure (HF) and is associated with adverse outcomes, including decreased quality of life, increased risk of hospitalization, and decreased survival. Intravenous ferric carboxymaltose (FCM) has been shown to improve outcomes among patients with HF and concomitant iron deficiency, but FCM is associated with an increased risk of hypophosphataemia. We aimed to better characterize this risk among HF populations. METHODS AND RESULTS This pooled analysis examined data from 41 studies of adults with iron deficiency across disease states and therapeutic areas. Among the 7931 patients treated with FCM available for analysis, 14% made up the HF subgroup. Additional subgroups included women's health (36%), non-dialysis-dependent chronic kidney disease (NDD-CKD; 27%), haemodialysis-dependent chronic kidney disease (HD-CKD; 1%), gastrointestinal (10%), neurology (3%), and other (10%). The incidence of post-baseline moderate or severe hypophosphataemia (i.e. serum phosphate [PO4 3- ] level <2.0 mg/dL) varied across the therapeutic areas, with the lowest incidences observed in the HD-CKD (0%), HF (8.1%), and NDD-CKD (12.8%) subgroups. The prevalence of moderate or severe hypophosphataemia among the women's health, other, gastrointestinal, and neurology subgroups was 30.1%, 40.6%, 51.0%, and 55.6%, respectively. In the HF subgroup, one patient (<0.1%) had a serum PO4 3- of <1.0 mg/dL recorded, compared with 4.8% and 4.0% of the subjects in the neurology and gastrointestinal groups, respectively. With the exception of the HD-CKD subgroup, mean serum PO4 3- levels decreased through weeks 2 to 4, and then returned toward baseline and plateaued by week 8. The strongest predictor of hypophosphataemia was preserved kidney function (estimated glomerular filtration rate: >60 mL/min/1.73 m2 vs. <30 mL/min/1.73 m2 ; odds ratio: 12.2). Among patients in the HF subgroup, the incidence of treatment-emergent adverse events potentially related to hypophosphataemia (e.g. cardiac failure, ventricular tachyarrhythmias, fatigue, muscle weakness, bone pain, neurological symptoms, and muscle pain) was lower among FCM-treated patients than among those receiving placebo, and lower among patients with a post-baseline PO4 3- <2 mg/dL vs. those not meeting such criteria. CONCLUSIONS The risk of laboratory-assessed hypophosphataemia in HF patients treated with FCM was lower than that seen in patients in other therapeutic areas treated with FCM, and clinical events associated with hypophosphataemia are uncommon with FCM therapy in this population. Appropriate monitoring, particularly soon after administration in the unlikely event of repeated dosing in HF patients, will allow for further refinement of management strategies. [Correction added on 24 February 2023, after first online publication: In the preceding sentence, "…administration, will allow…" has been corrected to "…administration in the unlikely event of repeated dosing in HF patients, will allow…" in this version.].
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Affiliation(s)
| | - Kamyar Kalantar‐Zadeh
- Division of Nephrology and Hypertension and Kidney TransplantationUniversity of CaliforniaIrvineCaliforniaUSA
| | - Ewa A. Jankowska
- Institute of Heart DiseasesWrocław Medical UniversityWrocławPoland
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Burstad KM, Cladis DP, Vorland CJ, Wastney ME, Biruete A, Dominguez JM, O'Neill KD, Chen NX, Moe SM, Hill Gallant KM. Acute High Dietary Phosphorus Following Low-Phosphorus Diet Acclimation Does Not Enhance Intestinal Fractional Phosphorus Absorption in Nephrectomized Male Rats. JBMR Plus 2022; 6:e10698. [PMID: 36530183 PMCID: PMC9751657 DOI: 10.1002/jbm4.10698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 10/05/2022] [Accepted: 10/27/2022] [Indexed: 05/21/2024] Open
Abstract
Dietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (n = 36) or sham operation (n = 36) were block-randomized to 1 of 3 diets: LP (0.1% P w/w), HP (1.2%), or LP followed by acute HP (LPHP 0.1% then 1.2%). Phosphorus absorption tests were conducted using 33P radioisotope administrated by oral gavage or intravenously (iv). Although the overall two-way ANCOVA model for intestinal fractional phosphorus absorption was non-significant, exploratory comparisons showed intestinal fractional phosphorus absorption efficiency tended to be higher in rats in the LP compared with HP or LPHP groups. Rats in the HP or LPHP groups had higher plasma phosphorus compared with rats in the LP group, but the LPHP group was not different from the HP group. Gene expression of the major intestinal phosphate transporter, NaPi-2b, was lower in the jejunum of rats in the LPHP group compared with rats in the HP group but not different in the duodenum. These results demonstrate that an acute HP load after acclimation to a LP diet does not lead to enhanced intestinal fractional phosphorus absorption efficiency in 5/6 nephrectomized male rats. These data provide evidence against the notion that dietary phosphorus restriction or binder use adversely increases absorption efficiency after a single instance of dietary or binder non-adherence. However, other adverse consequences of fluctuating dietary phosphorus intake cannot be ruled out. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Kendal M Burstad
- Department of Food Science and NutritionUniversity of MinnesotaSaint PaulMNUSA
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
| | - Dennis P Cladis
- Department of Food Science and NutritionUniversity of MinnesotaSaint PaulMNUSA
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
| | - Colby J Vorland
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
- Department of Applied Health ScienceIndiana University School of Public Health‐BloomingtonBloomingtonINUSA
| | - Meryl E Wastney
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
| | - Annabel Biruete
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
- Department of Nutrition and DieteticsIndiana University‐Purdue University IndianapolisIndianapolisINUSA
| | - James M Dominguez
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
| | - Kalisha D O'Neill
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
| | - Neal X Chen
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
| | - Sharon M Moe
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
- Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisINUSA
- Department of MedicineRoudebush Veterans Affairs Medicine CenterIndianapolisINUSA
| | - Kathleen M Hill Gallant
- Department of Food Science and NutritionUniversity of MinnesotaSaint PaulMNUSA
- Department of Nutrition SciencePurdue UniversityWest LafayetteINUSA
- Department of Medicine‐Division of NephrologyIndiana University School of MedicineIndianapolisINUSA
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Oda A, Tanaka K, Saito H, Iwasaki T, Watanabe S, Kimura H, Kazama S, Shimabukuro M, Asahi K, Watanabe T, Kazama JJ. Association between Serum Inorganic Phosphorus Levels and Adverse Outcomes in Chronic Kidney Disease: The Fukushima CKD Cohort Study. Intern Med 2022; 61:1653-1662. [PMID: 34803092 PMCID: PMC9259314 DOI: 10.2169/internalmedicine.7870-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.
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Affiliation(s)
- Akira Oda
- Department of Nephrology and Hypertension, Fukushima Medical University, Japan
| | - Kenichi Tanaka
- Department of Nephrology and Hypertension, Fukushima Medical University, Japan
- Division of Advanced Community Based Care for Lifestyle Related Diseases, Fukushima Medical University, Japan
| | - Hirotaka Saito
- Department of Nephrology and Hypertension, Fukushima Medical University, Japan
| | - Tsuyoshi Iwasaki
- Department of Nephrology and Hypertension, Fukushima Medical University, Japan
| | - Shuhei Watanabe
- Department of Nephrology and Hypertension, Fukushima Medical University, Japan
| | - Hiroshi Kimura
- Department of Nephrology and Hypertension, Fukushima Medical University, Japan
| | - Sakumi Kazama
- Division of Advanced Community Based Care for Lifestyle Related Diseases, Fukushima Medical University, Japan
| | - Michio Shimabukuro
- Division of Advanced Community Based Care for Lifestyle Related Diseases, Fukushima Medical University, Japan
- Department of Diabetes, Endocrinology and Metabolism, Fukushima Medical University, Japan
| | - Koichi Asahi
- Division of Advanced Community Based Care for Lifestyle Related Diseases, Fukushima Medical University, Japan
- Division of Nephrology and Hypertension, Iwate Medical University, Japan
| | - Tsuyoshi Watanabe
- Division of Advanced Community Based Care for Lifestyle Related Diseases, Fukushima Medical University, Japan
| | - Junichiro James Kazama
- Department of Nephrology and Hypertension, Fukushima Medical University, Japan
- Division of Advanced Community Based Care for Lifestyle Related Diseases, Fukushima Medical University, Japan
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Yin J, Yin J, Lian R, Li P, Zheng J. Implementation and effectiveness of an intensive education program on phosphate control among hemodialysis patients: a non-randomized, single-arm, single-center trial. BMC Nephrol 2021; 22:243. [PMID: 34210293 PMCID: PMC8252215 DOI: 10.1186/s12882-021-02441-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 06/04/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Hyperphosphatemia is a common complication in patients on maintenance hemodialysis. Patients' adherence to phosphorus control can be improved by consistent education. However, few studies have focused on the model construction and effects of health education on phosphate control for hemodialysis patients. OBJECTIVE To develop an intensive education program focusing on phosphate control among hemodialysis patients and to analyze the effectiveness of this program. DESIGN A non-randomized, single-arm, single-center trial lasting for 6 months. SETTING This program was conducted in a hemodialysis center in a teaching hospital in Zhuhai, China. PARTICIPANTS Patients on maintenance hemodialysis with hyperphosphatemia. METHODS An intensive hyperphosphatemia control education program lasting for 6 months was conducted among 366 hemodialysis patients applying the First Principles of Instruction model, which focused on mastering four stages: (a) activation of prior experience, (b) demonstration of skills, (c) application of skills and (d) integration of these skills into real-world activities. The controlled percentage of serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders before and after the education program were assessed. RESULTS The proportion of controlled serum phosphorus was significantly increased from 43.5 to 54.9% (P<0.001). The scores on the knowledge of phosphate control were improved significantly from 59.0 ± 18.9 to 80.6 ± 12.4 (P < 0.001). The proportion of high adherence to phosphate binders was increased dramatically from 21.9 to 44.5% (P < 0.001). CONCLUSION The intensive education program can effectively improve serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders among hemodialysis patients. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2100042017 . Retrospectively registered January 12th, 2021.
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Affiliation(s)
- Jinmei Yin
- Blood purification center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jun Yin
- Blood purification center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Rongli Lian
- Department of critical medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Peiqiu Li
- Blood purification center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jing Zheng
- School of Nursing, Guangdong Pharmaceutical University, 283 Jianghai Avenue, Guangzhou, 510310 Guangdong Province China
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Molina P, Gavela E, Vizcaíno B, Huarte E, Carrero JJ. Optimizing Diet to Slow CKD Progression. Front Med (Lausanne) 2021; 8:654250. [PMID: 34249961 PMCID: PMC8267004 DOI: 10.3389/fmed.2021.654250] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 05/31/2021] [Indexed: 12/15/2022] Open
Abstract
Due to the unique role of the kidney in the metabolism of nutrients, patients with chronic kidney disease (CKD) lose the ability to excrete solutes and maintain homeostasis. Nutrient intake modifications and monitoring of nutritional status in this population becomes critical, since it can affect important health outcomes, including progression to kidney failure, quality of life, morbidity, and mortality. Although there are multiple hemodynamic and metabolic factors involved in the progression and prognosis of CKD, nutritional interventions are a central component of the care of patients with non-dialysis CKD (ND-CKD) and of the prevention of overweight and possible protein energy-wasting. Here, we review the reno-protective effects of diet in adults with ND-CKD stages 3-5, including transplant patients.
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Affiliation(s)
- Pablo Molina
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, Spain
- Department of Medicine, Universitat de València, Valencia, Spain
| | - Eva Gavela
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, Spain
| | - Belén Vizcaíno
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, Spain
| | - Emma Huarte
- Department of Nephrology, Hospital San Pedro, Logroño, Spain
| | - Juan Jesús Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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Intestinal Chelators, Sorbants, and Gut-Derived Uremic Toxins. Toxins (Basel) 2021; 13:toxins13020091. [PMID: 33530404 PMCID: PMC7911578 DOI: 10.3390/toxins13020091] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/20/2021] [Accepted: 01/22/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) is a highly prevalent condition and is associated with a high comorbidity burden, polymedication, and a high mortality rate. A number of conventional and nonconventional risk factors for comorbidities and mortality in CKD have been identified. Among the nonconventional risk factors, uremic toxins are valuable therapeutic targets. The fact that some uremic toxins are gut-derived suggests that intestinal chelators might have a therapeutic effect. The phosphate binders used to prevent hyperphosphatemia in hemodialysis patients act by complexing inorganic phosphate in the gastrointestinal tract but might conceivably have a nonspecific action on gut-derived uremic toxins. Since phosphorous is a major nutrient for the survival and reproduction of bacteria, changes in its intestinal concentration may impact the gut microbiota’s activity and composition. Furthermore, AST-120 is an orally administered activated charcoal adsorbent that is widely used in Asian countries to specifically decrease uremic toxin levels. In this narrative review, we examine the latest data on the use of oral nonspecific and specific intestinal chelators to reduce levels of gut-derived uremic toxins.
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Nongnuch A, Petcharut J, Suksuwan W, Davenport A, Phuphuakrat A. Causes of hypercalcemia in people living with HIV in the HAART era. HIV Res Clin Pract 2020; 21:115-120. [PMID: 33076771 DOI: 10.1080/25787489.2020.1836900] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Hypercalcemia is an uncommon finding in people living with HIV (PLHIV). Causes of hypercalcemia in PLHIV have not been well documented. As such, we studied the causes of hypercalcemia in PLHIV. METHODS We conducted a retrospective review of PLHIV who had corrected serum calcium of ≥10.5 mg/dL between 2010 and 2019. Demographic data, associated diseases, and treatment details were collected. Corrected serum calcium levels were compared among the causes of hypercalcemia. RESULTS A total of 70 of 2168 (3.2%) PLHIV had hypercalcemia. Forty-nine (70.0%) were male with a mean age of 47.7 ± 4.7 years. Only two (2.9%) had symptoms of hypercalcemia. Fifty-four patients had identifiable causes of hypercalcemia; 21 infections (30.0%), 17 solid organ malignancies (24.3%), 14 hematologic malignancies (20.0%), and two other specific causes (2.9%). Mean corrected serum calcium concentrations of PLHIV who had solid organ malignancy, hematologic malignancy, infection, and unknown causes were 12.8 ± 2.1, 11.4 ± 1.0, 11.2 ± 0.6, and 10.8 ± 0.2 mg/dL, respectively. Corrected serum calcium levels were significantly greater in patients who had solid organ malignancy comparing to those with other causes of hypercalcemia (p < 0.05, all). Logistic regression identified solid organ malignancy as the only factor associated with moderate to severe hypercalcemia (odds ratio 12.72, 95% confidence interval 3.11-52.08; p < 0.001). CONCLUSIONS Hypercalcemia in PLHIV is associated with solid organ malignancy, hematologic malignancy, and infection. Most PLHIV with hypercalcemia are asymptomatic. Solid organ malignancy is associated with moderate to severe hypercalcemia, and as such PLHIV presenting with moderate to severe hypercalcemia should be investigated for solid organ malignancy.
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Affiliation(s)
- Arkom Nongnuch
- Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Jutatip Petcharut
- Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Worramin Suksuwan
- Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Andrew Davenport
- UCL Centre for Nephrology, Royal Free Hospital, University College London, London, UK
| | - Angsana Phuphuakrat
- Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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10
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Pekar JD, Grzych G, Durand G, Haas J, Lionet A, Brousseau T, Glowacki F, Maboudou P. Calcium state estimation by total calcium: the evidence to end the never-ending story. Clin Chem Lab Med 2020; 58:222-231. [PMID: 31473684 DOI: 10.1515/cclm-2019-0568] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Accepted: 08/07/2019] [Indexed: 01/31/2023]
Abstract
Background Total blood calcium (TCa) is routinely used to diagnose and manage mineral and bone metabolism disorders. Numerous laboratories adjust TCa by albumin, though literature suggests there are some limits to this approach. Here we report a large retrospective study on agreement rate between ionized calcium (iCa) measurement and TCa or albumin-adjusted calcium measurements. Methods We retrospectively selected 5055 samples with simultaneous measurements of iCa, TCa, albumin and pH. We subgrouped our patients according to their estimated glomerular filtration rate (eGFR), albumin levels and pH. We analyzed each patient's calcium state with iCa as reference to determine agreement rate with TCa and albumin-adjusted calcium using Payne, Clase, Jain and Ridefelt formulas. Results The Payne formula performed poorly in patients with abnormal albumin, eGFR or pH levels. In patients with low albumin levels or blood pH disorders, Payne-adjusted calcium may overestimate the calcium state in up to 80% of cases. Similarly, TCa has better agreement with iCa in the case of hypoalbuminemia, but performed similarly to the Payne formula in patients with physiological albumin levels. The global agreement rate for Clase, Jain and Ridefelt formulas suggests significant improvement compared to Payne calcium adjustment but no significant improvement compared to TCa. Conclusions Total and albumin-adjusted calcium measurement leads to a misclassification of calcium status. Moreover, accurate calcium state determination depends on blood pH levels, whose measurement requires the same pre-analytical restrictions as iCa measurement. We propose that iCa should instead become the reference method to determine the real calcium state.
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Affiliation(s)
| | - Guillaume Grzych
- Centre de Biologie Pathologie, Laboratoire d'Hormonologie, Métabolisme-Nutrition, Oncologie, rue du Pr J. Leclercq, CHU Lille, F-59000 Lille, France.,Université de Lille, INSERM UMR-1011, Lille, France
| | - Gatien Durand
- CHU Lille, UF 8832 Biochimie automatisée, Lille, France
| | - Joël Haas
- Université de Lille, INSERM UMR-1011, Lille, France
| | - Arnaud Lionet
- CHU Lille, Service de Néphrologie et Transplantation, Lille, France
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11
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Increased Serum Parathyroid Hormone, Osteocalcin and Alkaline Phosphatase Are Associated with a Long-Term Adverse Cardiovascular Outcome after Coronary Artery Bypass Graft Surgery. Diagnostics (Basel) 2019; 9:diagnostics9040143. [PMID: 31597282 PMCID: PMC6963598 DOI: 10.3390/diagnostics9040143] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 10/03/2019] [Accepted: 10/05/2019] [Indexed: 01/03/2023] Open
Abstract
Despite the fact that an association of osteopoenia/osteoporosis with elevated risk of coronary artery calcification (CAC) and coronary atherosclerosis (CA) is well-established, it remains unclear whether bone turnover markers can be employed in long-term prognostication of such patients. Here we measured serum calcium, phosphate, calcitonin, parathyroid hormone (PTH), osteoprotegerin, osteocalcin, osteopontin, alkaline phosphatase and its bone isoenzyme, subsequently correlating them with an adverse cardiovascular outcome after 3 years of follow-up. The extent of brachiocephalic artery stenosis, CA, or CAC, as well as prevalence of osteopoenia/osteoporosis before the coronary artery bypass graft (CABG) surgery, did not differ between outcome groups, suggesting that subtle molecular mechanisms might be involved in determining the outcome rather than clinical or subclinical disease. After stepwise logistic regression, serum osteocalcin > 26.8 ng/mL and PTH > 49.1 pg/mL were independent predictors of an adverse outcome. Serum ionised calcium correlated with multivessel coronary artery disease; moreover, patients with severe CA (SYNTAX score > 21) had higher serum ionised calcium than those with mild CA. Likewise, serum alkaline phosphatase was associated with severe CA and CAC (Agatston score > 400). In conclusion, serum PTH, osteocalcin, and alkaline phosphatase are associated with an adverse cardiovascular outcome 3 years after CABG surgery regardless of osteopoenia/osteoporosis, coronary/peripheral atherosclerosis, and CAC.
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12
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Whittaker CF, Miklich MA, Patel RS, Fink JC. Medication Safety Principles and Practice in CKD. Clin J Am Soc Nephrol 2018; 13:1738-1746. [PMID: 29915131 PMCID: PMC6237057 DOI: 10.2215/cjn.00580118] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Ensuring patient safety is a priority of medical care because iatrogenic injury has been a primary concern. Medications are an important source of medical errors, and kidney disease is a thoroughfare of factors threatening safe administration of medicines. Principal among these is reduced kidney function because almost half of all medications used are eliminated via the kidney. Additionally, kidney patients often suffer from multimorbidity, including diabetes, hypertension, and heart failure, with a range of prescribers who often do not coordinate treatments. Patients with kidney disease are also susceptible to further kidney injury and metabolic derangements from medications, which can worsen the disease. In this review, we will present the key issues and threats to safe medication use in kidney disease, with a focus on predialysis CKD, as the scope of medication safety in ESKD and transplantation are unique and deserve their own consideration. We discuss drugs that need to be avoided or dose modified, and review the complications of a range of medications routinely administered in CKD, as these also call for cautious use.
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Affiliation(s)
- Chanel F. Whittaker
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland
| | - Margaret A. Miklich
- Department of Pharmacy Practice, Temple University School of Pharmacy, Philadelphia, Pennsylvania
| | - Roshni S. Patel
- Department of Pharmacy Practice, Jefferson College of Pharmacy, Philadelphia, Pennsylvania; and
| | - Jeffrey C. Fink
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
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13
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Borrelli S, Chiodini P, De Nicola L, Minutolo R, Provenzano M, Garofalo C, Remuzzi G, Ronco C, Cozzolino MG, Manno C, Costanzo AM, Gualberti G, Conte G. Prognosis and determinants of serum PTH changes over time in 1-5 CKD stage patients followed in tertiary care. PLoS One 2018; 13:e0202417. [PMID: 30138402 PMCID: PMC6107171 DOI: 10.1371/journal.pone.0202417] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 08/02/2018] [Indexed: 01/16/2023] Open
Abstract
International Guidelines for mineral bone disorders recommend that in Non Dialytic-Chronic Kidney Disease (ND-CKD) clinical decisions should be based on the trend of serum PTH changes over time rather than on a single value. However, the prognostic impact of these changes in ND-CKD patients remains unknown. We performed a multicenter cohort study in ND-CKD patients (stage 1-5) followed for 36 months in 24 Italian Nephrology Units. PTH changes (ΔPTH) were defined as the absolute differences between all available PTH measurements following the first control and basal value. Primary endpoint in this subanalysis was renal death (End-Stage Renal Disease (ESRD) or all-causes death before ESRD). Association between renal death and ΔPTH was assessed by time-dependent Cox model for repeated measurements. Out of the original cohort (N = 884), we selected 543 patients (66.3±15.4 ys, 58.4% males) with at least two serum PTH measurements. At baseline, eGFR was 36 (IQR: 22.4-56.8) mL/min/1.73m2 and serum PTH 46 (IQR: 28-81) pg/mL. ΔPTH was in median 0 (IQR:-18/18) pg/mL. Basal predictors of longitudinal PTH increments were higher serum phosphate, more advanced CKD stages and lower serum PTH. Fully adjusted Cox model with ΔPTH quartiles as discrete time-dependent covariate showed a significant risk of renal death in the highest quartile (HR: 1.91; 95%CI:1.08-3.38; P = 0.026). Considering ΔPTH, as continuous time-dependent variable, (HR:1.02; 95%C.I.: 1.01-1.04; P = 0.004), risk of renal death progressively rose as ΔPTH increased. An increment in serum PTH over time is associated with a worse prognosis in ND-CKD patients, independently from baseline or any absolute concentration of serum PTH and phosphate.
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Affiliation(s)
- Silvio Borrelli
- Division of Nephrology, University of Campania "Luigi Vanvitelli, Naples, Italy
| | - Paolo Chiodini
- Medical Statistics Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Luca De Nicola
- Division of Nephrology, University of Campania "Luigi Vanvitelli, Naples, Italy
| | - Roberto Minutolo
- Division of Nephrology, University of Campania "Luigi Vanvitelli, Naples, Italy
| | - Michele Provenzano
- Division of Nephrology, University of Campania "Luigi Vanvitelli, Naples, Italy
| | - Carlo Garofalo
- Division of Nephrology, University of Campania "Luigi Vanvitelli, Naples, Italy
| | - Giuseppe Remuzzi
- IRCCS—Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy
- Unit of Nephrology, Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Claudio Ronco
- Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV) San Bortolo Hospital, Vicenza–Italy
| | - Mario Gennaro Cozzolino
- Department of Health Sciences, Renal Division, ASST Santi Paolo e Carlo, University of Milan, Italy
| | - Carlo Manno
- Unità Operativa Complessa Nefrologia, Dialisi e Trapianti, Dipartimento Emergenza e Trapianti d’Organo, Università degli Studi “Aldo Moro”, Bari, Italy
| | | | | | - Giuseppe Conte
- Division of Nephrology, University of Campania "Luigi Vanvitelli, Naples, Italy
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14
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Kim J, Lee J, Kim KN, Oh KH, Ahn C, Lee J, Kang D, Park SK. Association between Dietary Mineral Intake and Chronic Kidney Disease: The Health Examinees (HEXA) Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:ijerph15061070. [PMID: 29795052 PMCID: PMC6025644 DOI: 10.3390/ijerph15061070] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 05/11/2018] [Accepted: 05/11/2018] [Indexed: 01/20/2023]
Abstract
Few studies have explored the association between mineral intake and chronic kidney disease (CKD). A cross-sectional analysis investigated the association between mineral intake (calcium, phosphorus, sodium, potassium, iron, and zinc) and CKD using the Health Examinee (HEXA) cohort of the Korean Genome and Epidemiologic Study (KoGES). For 159,711 participants, mineral intake was assessed by a food frequency questionnaire. CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2. Dietary intake of each mineral was divided into quartiles and the quartile including recommended dietary allowance (RDA) or adequate intake (AI) of each mineral was used as a reference. We assessed the association between the quartile of mineral intakes and CKD using polytomous logistic regression models. The lowest quartiles of phosphorus (≤663.68 mg/day, odds ratio [OR] = 1.64, 95% confidence interval [CI]: 1.25–2.15), potassium (≤1567.53 mg/day, OR = 1.87, 95% CI: 1.27–2.75), iron (≤6.93 mg/day, OR = 1.53, 95% CI: 1.17–2.01), and zinc (≤5.86 mg/day, OR = 1.52, 95% CI: 1.02–2.26) were associated with higher odds for advanced CKD compared with the references. The present study suggests that an inadequate intake of some minerals may be associated with CKD occurrence in the general population. Due to the reverse causation issue in this cross-sectional study design, further longitudinal prospective studies are needed in order to prove the results.
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Affiliation(s)
- Jeewoo Kim
- Department of Medicine, College of Medicine, Seoul National University, 103 Daehakro, Jongnogu, Seoul 03080, Korea.
| | - Juyeon Lee
- Department of Preventive Medicine, College of Medicine, Seoul National University, 103 Daehakro, Jongnogu, Seoul 03080, Korea.
- Department of Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongnogu, Seoul 03080, Korea.
- Cancer Research Institute, Seoul National University, 103 Daehakro, Jongnogu, Seoul 03080, Korea.
| | - Kyoung-Nam Kim
- Division of Public Health and Preventive Medicine, Seoul National University Hospital, 101 Daehakro, Jongnogu, Seoul 03080, Korea.
| | - Kook-Hwan Oh
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehakro, Jongnogu, Seoul 03080, Korea.
| | - Curie Ahn
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehakro, Jongnogu, Seoul 03080, Korea.
| | - Jongkoo Lee
- JW Lee Center for Global Medicine, College of Medicine, Seoul National University, IhwaJang-gil 71 Jongnogu, Seoul 03087, Korea.
- Department of Family Medicine, Seoul National University Hospital, 101 Daehakro, Jongnogu, Seoul 03080, Korea.
| | - Daehee Kang
- Department of Preventive Medicine, College of Medicine, Seoul National University, 103 Daehakro, Jongnogu, Seoul 03080, Korea.
- Department of Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongnogu, Seoul 03080, Korea.
| | - Sue K Park
- Department of Preventive Medicine, College of Medicine, Seoul National University, 103 Daehakro, Jongnogu, Seoul 03080, Korea.
- Department of Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongnogu, Seoul 03080, Korea.
- Cancer Research Institute, Seoul National University, 103 Daehakro, Jongnogu, Seoul 03080, Korea.
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15
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Sakaguchi Y, Hamano T, Isaka Y. Magnesium and Progression of Chronic Kidney Disease: Benefits Beyond Cardiovascular Protection? Adv Chronic Kidney Dis 2018; 25:274-280. [PMID: 29793667 DOI: 10.1053/j.ackd.2017.11.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 11/12/2017] [Accepted: 11/15/2017] [Indexed: 12/16/2022]
Abstract
Experimental and clinical studies have demonstrated that magnesium deficiency leads to hypertension, insulin resistance, and endothelial dysfunction, and is associated with an increased risk of cardiovascular events. Given that cardiovascular disease and CKD share similar risk factors, the low magnesium status may also contribute to CKD progression. In fact, lower serum magnesium levels and lower dietary magnesium intake are associated with an increased risk of incident CKD and progression to end-stage kidney disease. Because these associations are independent of traditional risk factors, other pathways might be involved in the relationship between magnesium deficiency and the risk of CKD progression. Recent evidence has shown that magnesium suppresses phosphate-induced vascular calcification. Magnesium impairs the crystallization of calcium phosphate-more specifically, the maturation of calciprotein particles. Considering that phosphate overload causes kidney damage, magnesium might counteract the phosphate toxicity to the kidney, as in the case of vascular calcification. This hypothesis is supported by an in vitro observation that magnesium alleviates proximal tubular cell injury induced by high phosphate. Potential usefulness of magnesium as a treatment option for phosphate toxicity in CKD should be further investigated by intervention studies.
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16
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Phosphate and Cardiovascular Disease beyond Chronic Kidney Disease and Vascular Calcification. Int J Nephrol 2018; 2018:3162806. [PMID: 29850246 PMCID: PMC5911324 DOI: 10.1155/2018/3162806] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 03/06/2018] [Indexed: 12/13/2022] Open
Abstract
Phosphate is essential for life but its accumulation can be detrimental. In end-stage renal disease, widespread vascular calcification occurs as a result of chronic phosphate load. The accumulation of phosphate is likely to occur long before the rise in serum phosphate above the normal range since several observational studies in both general population and early-stage CKD patients have identified the relationship between high-normal serum phosphate and adverse cardiovascular outcomes. Consumption of food high in phosphate increases both fasting and postprandial serum phosphate and habitual intake of high phosphate diet is associated with aging, cardiac hypertrophy, endothelial dysfunction, and subclinical atherosclerosis. The decline in renal function and dietary phosphate load can increase circulating fibroblast growth factor-23 (FGF-23) which may have a direct impact on cardiomyocytes. Increased FGF-23 levels in both CKD and general populations are associated with left ventricular hypertrophy, congestive heart failure, atrial fibrillation, and mortality. Increased extracellular phosphate directly affects endothelial cells causing cell apoptosis and vascular smooth muscle cells (VSMCs) causing transformation to osteogenic phenotype. Excess of calcium and phosphate in the circulation can promote the formation of protein-mineral complex called calciprotein particles (CPPs). In CKD, these CPPs contain less calcification inhibitors, induce inflammation, and promote VSMC calcification.
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17
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Prakobsuk S, Sirilak S, Vipattawat K, Taweesedt PT, Sumethkul V, Kantachuvesiri S, Disthabanchong S. Hyperparathyroidism and increased fractional excretion of phosphate predict allograft loss in long-term kidney transplant recipients. Clin Exp Nephrol 2017; 21:926-931. [PMID: 27981393 DOI: 10.1007/s10157-016-1370-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Accepted: 12/01/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND After kidney transplantation, fibroblast growth factor-23 (FGF-23) normally returns to baseline within 1 year whereas hyperparathyroidism persists in most kidney transplant (KT) recipients. As a result, serum phosphate remains relatively low in association with increased serum calcium and urinary phosphate excretion when compared to chronic kidney disease patients. The relationship between mineral metabolism and outcomes in long-term KT recipients has not been extensively studied. This study investigated whether the alteration in mineral metabolism influenced graft survival in long-term KT recipients. METHODS This study included 273 KT recipients after 1 year of transplantation. Mineral parameters were obtained at the time of enrolment and patients were followed prospectively for an average of 71 months. RESULTS Graft loss (death-censored) occurred in 41 (15%) patients. In univariate analysis, deceased donor transplantation, decreased serum albumin and estimated glomerular filtration rate, increased serum phosphate, parathyroid hormone (PTH), FGF-23 and fractional excretion of phosphate (FePi) predicted future allograft loss. After adjustments for cardiovascular disease risk factors, donor type, dialysis vintage, serum albumin and allograft function, only increased PTH and FePi remained associated with the outcome. Relationships between increased serum phosphate and FGF-23 with graft survival were lost after adjustments. Adjusted survival curves revealed the association between PTH > 90 pg/mL and FePi > 20% with worse graft survival. CONCLUSIONS Hyperparathyroidism and increased FePi predicted allograft loss in long-term KT recipients.
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Affiliation(s)
- Sumanee Prakobsuk
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, 7th floor, Building 1, Phayathai, Bangkok, 10400, Thailand
| | - Supinda Sirilak
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, 7th floor, Building 1, Phayathai, Bangkok, 10400, Thailand
| | - Kotcharat Vipattawat
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, 7th floor, Building 1, Phayathai, Bangkok, 10400, Thailand
| | - Pahnwat T Taweesedt
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, 7th floor, Building 1, Phayathai, Bangkok, 10400, Thailand
| | - Vasant Sumethkul
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, 7th floor, Building 1, Phayathai, Bangkok, 10400, Thailand
| | - Surasak Kantachuvesiri
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, 7th floor, Building 1, Phayathai, Bangkok, 10400, Thailand
| | - Sinee Disthabanchong
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, 7th floor, Building 1, Phayathai, Bangkok, 10400, Thailand.
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18
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KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011) 2017; 7:1-59. [PMID: 30675420 PMCID: PMC6340919 DOI: 10.1016/j.kisu.2017.04.001] [Citation(s) in RCA: 1072] [Impact Index Per Article: 134.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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19
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A Review of Phosphate Binders in Chronic Kidney Disease: Incremental Progress or Just Higher Costs? Drugs 2017; 77:1155-1186. [DOI: 10.1007/s40265-017-0758-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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20
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Effects of Magnesium on the Phosphate Toxicity in Chronic Kidney Disease: Time for Intervention Studies. Nutrients 2017; 9:nu9020112. [PMID: 28178182 PMCID: PMC5331543 DOI: 10.3390/nu9020112] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 01/20/2017] [Accepted: 02/03/2017] [Indexed: 12/18/2022] Open
Abstract
Magnesium, an essential mineral for human health, plays a pivotal role in the cardiovascular system. Epidemiological studies in the general population have found an association between lower dietary magnesium intake and an elevated risk of cardiovascular events. In addition, magnesium supplementation was shown to improve blood pressure control, insulin sensitivity, and endothelial function. The relationship between magnesium and cardiovascular prognosis among patients with chronic kidney disease (CKD) has been increasingly investigated as it is becoming evident that magnesium can inhibit vascular calcification, a prominent risk of cardiovascular events, which commonly occurs in CKD patients. Cohort studies in patients receiving dialysis have shown a lower serum magnesium level as a significant risk for cardiovascular mortality. Interestingly, the cardiovascular mortality risk associated with hyperphosphatemia is alleviated among those with high serum magnesium levels, consistent with in vitro evidence that magnesium inhibits high-phosphate induced calcification of vascular smooth muscle cells. Furthermore, a harmful effect of high phosphate on the progression of CKD is also attenuated among those with high serum magnesium levels. The potential usefulness of magnesium as a remedy for phosphate toxicity should be further explored by future intervention studies.
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21
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Ribitsch W, Schilcher G, Quehenberger F, Pilz S, Portugaller RH, Truschnig-Wilders M, Zweiker R, Brodmann M, Stiegler P, Rosenkranz AR, Pickering JW, Horina JH. Neutrophil gelatinase-associated lipocalin (NGAL) fails as an early predictor of contrast induced nephropathy in chronic kidney disease (ANTI-CI-AKI study). Sci Rep 2017; 7:41300. [PMID: 28128223 PMCID: PMC5269674 DOI: 10.1038/srep41300] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 12/16/2016] [Indexed: 01/25/2023] Open
Abstract
The aim of the study was to evaluate the diagnostic accuracy of urinary neutrophil gelatinase- associated lipocalin (uNGAL) in patients with chronic kidney disease (CKD) as an early biomarker for contrast induced acute kidney injury (CI-AKI) and to investigate whether patients with an uNGAL increase might benefit from an additional intravenous volume expansion with regard to CI-AKI-incidence. We performed a prospective randomized controlled trial in 617 CKD-patients undergoing intra-arterial angiography. Urinary NGAL was measured the day before and 4-6hrs after angiography. In the event of a significant rise of uNGAL patients were randomized either into Group A, who received intravenous saline post procedure or Group B, who did not receive post-procedural i.v. fluids. Ten patients (1.62%) exhibited a significant rise of uNGAL after angiography and were randomized of whom one developed a CI-AKI. In the entire cohort the incidence of CI-AKI was 9.4% (58 patients) resulting in a specificity of 98.4% (95% CI: 97.0-99.3%) and a sensitivity of 1.72% (95% CI: 0.044-9.2%) of uNGAL for the diagnosis of CI-AKI. In this study uNGAL failed to predict CI-AKI and was an inadequate triage tool to guide an early intervention strategy to prevent CI-AKI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01292317.
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Affiliation(s)
- Werner Ribitsch
- Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz (MUG), Austria
| | - Gernot Schilcher
- Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz (MUG), Austria.,Intensive Care Unit, Department of Internal Medicine, MUG, Austria
| | - Franz Quehenberger
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria
| | - Stefan Pilz
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Austria
| | - Rupert H Portugaller
- Department of Vascular and Interventional Radiology, University Clinic of Radiology, Medical University of Graz, Austria
| | - Martini Truschnig-Wilders
- Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria
| | - Robert Zweiker
- Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Austria
| | - Marianne Brodmann
- Division of Angiology, Department of Internal Medicine, Medical University of Graz, Austria
| | - Philipp Stiegler
- Division of Transplantation Surgery, Medical University of Graz, Austria
| | - Alexander R Rosenkranz
- Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz (MUG), Austria
| | - John W Pickering
- Department of Medicine, University of Otago Christchurch and Emergency Medicine Department, Christchurch Hospital, Christchurch, New Zealand
| | - Joerg H Horina
- Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz (MUG), Austria
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22
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Dhondup T, Qian Q. Electrolyte and Acid-Base Disorders in Chronic Kidney Disease and End-Stage Kidney Failure. Blood Purif 2017; 43:179-188. [PMID: 28114143 DOI: 10.1159/000452725] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The kidneys play a pivotal role in the regulation of electrolyte and acid-base balance. With progressive loss of kidney function, derangements in electrolytes and acid-base inevitably occur and contribute to poor patient outcomes. As chronic kidney disease (CKD) has become a worldwide epidemic, medical providers are increasingly confronted with such problems. Adequate diagnosis and treatment will minimize complications and can potentially be lifesaving. In this review, we discuss the current understanding of the disease process, clinical presentation, diagnosis and treatment strategies, integrating up-to-date knowledge in the field. Although electrolyte and acid-base derangements are significant causes of morbidity and mortality in CKD and end-stage renal disease patients, they can be effectively managed through a timely institution of combined preventive measures and pharmacological therapy. Exciting advances and several upcoming outcome trials will provide further information to guide treatment and improve patient outcomes.
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Affiliation(s)
- Tsering Dhondup
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, College of Medicine, Rochester, MN, USA
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Retarding Chronic Kidney Disease (CKD) Progression: A Practical Nutritional Approach for Non-Dialysis CKD. ACTA ACUST UNITED AC 2016. [DOI: 10.5301/pocj.5000207] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
This is a case report on a patient with non-dialysis chronic kidney disease (CKD) in whom several nutritional issues are briefly discussed from a practical point of view. The article is accompanied by an editorial published in this Journal in relation to the 2nd International Conference of the European Renal Nutrition working group at ERA-EDTA—“Retarding CKD progression: readily available through comprehensive nutritional management?”— and focuses on several practical topics associated with the nutritional approach for the conservative treatment of non-dialysis CKD. The article is divided into 3 sections—basic nutritional assessment, nutritional targets, and nutritional follow-up in non-dialysis CKD—linked to 3 consecutive steps of the clinical follow-up of the patient and the related nutritional concerns and intervention. First visit: Baseline nutritional assessment and basic nutritional considerations in non-dialysis chronic kidney disease (CKD) • What nutritional assessment/monitoring for protein-energy wasting (PEW) should be employed? • Is a body mass index (BMI) of 21 kg/m2 adequate? • What phosphate target should be pursued? • What are the nutritional habits in patients with incident CKD? • What protein needs and amount of dietary protein should be pursued? • Does the quality of protein matter? • What amount of dietary salt should be employed? How should this be obtained? • How should normal serum phosphate be achieved? • What diet should be recommended? Is a vegetarian diet an option? Second visit: Major nutritional targets in non-dialysis CKD • Consequences of unintentional weight loss • What is the role of the renal dietitian in helping the patient adhere to a renal diet? Intermediate visits: Nutritional follow-up in non-dialysis CKD • What treatment for calcium/parathyroid hormone (PTH) will affect CKD progression? Final visits: • Would a dietary recall/intensive dietary education improve adherence with the diet? • Would a very-low-protein diet (VLPD)/ketodiet be indicated for this patient?
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Tangkiatkumjai M, Walker DM, Praditpornsilpa K, Boardman H. Association between medication adherence and clinical outcomes in patients with chronic kidney disease: a prospective cohort study. Clin Exp Nephrol 2016; 21:504-512. [PMID: 27438073 DOI: 10.1007/s10157-016-1312-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Accepted: 07/10/2016] [Indexed: 01/30/2023]
Abstract
BACKGROUND There is limited evidence of medication adherence related to progression of chronic kidney disease (CKD) worldwide. The aim of this study was to determine associations between medication adherence and the progression of CKD in outpatients with CKD. METHODS This cohort study recruited 339 Thai patients with stages 3-5 CKD. Patients with a glomerular disease or receiving renal replacement therapy before recruitment were excluded. 295 were followed up regarding their serum creatinine, blood pressure, glycated hemoglobin, and low-density lipoprotein cholesterol over 12 months. Medication adherence was measured at baseline using the Thai version of the 8-Item Morisky Medication Adherence Scale®. The primary outcome was the progression of CKD. The progression of CKD was defined as either a decline in estimated glomerular filtration rate of at least 3 ml/min/1.73 m2/year or initiation of renal replacement therapy. Univariate and multivariate analyses were performed using Chi-squared tests and multiple logistic regressions. RESULTS Twenty-one percent had poor adherence. Younger patients were more likely to have poor adherence (adjusted OR 2.81, 95 % CI 1.45-5.43). Anti-hypertensive agents were the most frequently reported as not being taken (52 %). Patients with poor adherence were associated with the progression of CKD (adjusted OR 1.96, 95 % CI 1.02-3.76). Those with poor adherence were less likely to control their blood pressure, than moderate-to-high adherence group (p < 0.01). CONCLUSION The findings suggest that CKD patients with poor medication adherence are more likely to have progression of CKD. Health care providers should acknowledge these findings and provide effective strategies to deal with this issue.
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Affiliation(s)
- Mayuree Tangkiatkumjai
- Division of Clinical Pharmacy, Faculty of Pharmacy, Srinakharinwirot University, Nakhonnayok, 26120, Thailand.
| | - Dawn-Marie Walker
- School of Health Sciences, University of Southampton, Southampton, UK
| | - Kearkiat Praditpornsilpa
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Helen Boardman
- Division of Social Research in Medicines and Health, School of Pharmacy, University of Nottingham, Nottingham, UK
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Căpuşă C, Chirculescu B, Vladu I, Viaşu L, Lipan M, Moţa E, Mircescu G. THE PREVALENCE OF BIOCHEMICAL ABNORMALITIES OF CHRONIC KIDNEY DISEASE. MINERAL AND BONE DISORDERS IN UNTREATED NON-DIALYSIS PATIENTS - A MULTICENTER STUDY. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2016; 12:282-290. [PMID: 31149102 PMCID: PMC6535263 DOI: 10.4183/aeb.2016.282] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND There are scarce data about prevalence of mineral metabolism (MM) disorders in Romanian predialysis patients, so we assessed their occurrence and relationships in mild to severe chronic kidney disease (CKD). METHODS One hundred fifteen non-dialysis CKD (eGFR 31, 95% CI 29-35mL/min) and 33 matched non-CKD subjects entered this multicentric, cross-sectional study. Serum 25-hydroxyvitamin D (25OHD), intact parathyroid hormone (iPTH), phosphate (PO4), total calcium (tCa) and alkaline phosphatase (AP) were measured, along with demographic and past medical history data. RESULTS Hypovitaminosis D was equally prevalent in Controls and CKD (91% vs. 96% had 25OHD<30ng/mL). Increasing proportions of hyperparathyroidism (33% - stage 2 to 100% - stage 5; p<0.001) and hyperphosphatemia (2% - stage 3 to 38% - stage 5; p<0.001) were found. Hypocalcemia was more prevalent in stage 5 (25% vs. 6% in stage 4, none in stage 3 and Controls, p<0.001). Mineral metabolism parameters correlated with eGFR. In addition, iPTH was directly associated with PO4, AP, and urinary albumin-to-creatinine ratio (ACR), but inversely with tCa and 25OHD, while negative correlation of 25OHD with age, AP, ACR, and C-reactive protein emerged. In multiple regression, eGFR was the only predictor of iPTH (Beta -0.68, 95%CI -1.35 to -0.90, R2 0.46, p<0.001), whereas age and ACR were the determinants of 25OHD (a model which explained 14% of its variation). CONCLUSIONS Hypovitaminosis D was very common irrespective of CKD presence and severity, and it seems worsened by older age and higher albuminuria. Hyperparathyroidism preceded hyperphosphatemia and hypocalcemia, and it seems mostly dependent on kidney function decline.
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Affiliation(s)
- C. Căpuşă
- “Carol Davila” University of Medicine and Pharmacy, Nephrology Dept., Bucharest, Romania
- “Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - B. Chirculescu
- “Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - I. Vladu
- Emergency County Hospital, Nephrology Dept., Craiova, Romania
| | - L. Viaşu
- “Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - M. Lipan
- “Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - E. Moţa
- Emergency County Hospital, Nephrology Dept., Craiova, Romania
| | - G. Mircescu
- “Carol Davila” University of Medicine and Pharmacy, Nephrology Dept., Bucharest, Romania
- “Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
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Sultana J, Musazzi UM, Ingrasciotta Y, Giorgianni F, Ientile V, Fontana A, Minghetti P, Perrotta M, Santoro D, Savica V, Trifirò G. Medication is an additional source of phosphate intake in chronic kidney disease patients. Nutr Metab Cardiovasc Dis 2015; 25:959-967. [PMID: 26165250 DOI: 10.1016/j.numecd.2015.06.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 05/05/2015] [Accepted: 06/01/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND AND AIMS Hyperphosphatemia increases the risk of cardiovascular morbidity but the use of medicines as a source of phosphate has not been investigated yet. This study aims to explore the use of absorbable phosphate-containing drugs in CKD patients. METHODS AND RESULTS Incident CKD patients were identified within the Arianna database (containing data from 158,510 persons in Caserta (Southern Italy) registered with 123 general practitioners) from 2005 to 2011. Drugs prescribed to these patients were classified as phosphate-containing based on the summary of product characteristics (SPC), PubChem and Micromedex. The number and duration of prescriptions for these drugs as well as the overall intake of phosphate were estimated. Out of 1989 CKD patients, 1381 (70%) were prescribed 266 medicinal products containing absorbable phosphate over a median follow-up of 6 years (interquartile range (IQR) = 5.2-6.0). Most patients were prescribed ATC A (650; 47.1%) and C (660; 47.8%) phosphate-containing drug products targeting the gastrointestinal and cardiovascular system for a median of 232 (IQR: 56-656) and 224 (IQR: 56-784) days respectively. CONCLUSIONS Several medications, especially chronically prescribed ones, contain absorbable phosphate. This study's findings confirm the relevance of medicines as a phosphate source for the first time.
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Affiliation(s)
- J Sultana
- Department of Clinical and Experimental Medicine, University of Messina, Italy
| | - U M Musazzi
- Department of Pharmaceutical Sciences, University of Milan, Italy
| | - Y Ingrasciotta
- Department of Clinical and Experimental Medicine, University of Messina, Italy
| | - F Giorgianni
- Department of Clinical and Experimental Medicine, University of Messina, Italy
| | - V Ientile
- Department of Clinical and Experimental Medicine, University of Messina, Italy
| | - A Fontana
- Unit of Biostatistics, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia, Italy
| | - P Minghetti
- Department of Pharmaceutical Sciences, University of Milan, Italy
| | - M Perrotta
- Caserta Local Health Service, Caserta, Italy
| | - D Santoro
- Department of Clinical and Experimental Medicine, University of Messina, Italy
| | - V Savica
- Department of Clinical and Experimental Medicine, University of Messina, Italy
| | - G Trifirò
- Department of Clinical and Experimental Medicine, University of Messina, Italy.
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Tangkiatkumjai M, Boardman H, Praditpornsilpa K, Walker DM. Association of herbal and dietary supplements with progression and complications of chronic kidney disease: A prospective cohort study. Nephrology (Carlton) 2015; 20:679-687. [PMID: 26040915 DOI: 10.1111/nep.12531] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/31/2015] [Indexed: 11/30/2022]
Abstract
AIM To determine associations between herbal and dietary supplement (HDS) use and the progression of chronic kidney disease (CKD), and associations of HDS with uncontrolled hyperphosphataemia in patients with CKD. METHOD The cohort study recruited 406 Thai outpatients with stage 3-5 CKD from two kidney clinics of which 357 were followed up over 12 months. Patients receiving renal replacement therapy prior to recruitment were excluded. Participants were interviewed regarding their HDS use, dietary intake and conventional medication adherence using a questionnaire. The primary outcome was a composite of a decline of at least 5 mL/min per 1.73 m2 per year of estimated glomerular filtration rate and end stage renal disease. Serum creatinine, serum levels of potassium and phosphate were extracted from their medical notes over the 12 months. χ2 tests and multiple logistic regression analyses were performed to ascertain any associations. RESULTS Despite no association between HDS and the progression of CKD over a one-year period (adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 0.66-2.03), two patients had acute kidney injury, which may be related to an unknown Chinese herbal medicine, or river spiderwort combined with diclofenac reported in the medical notes. The use of HDS was associated with uncontrolled hyperphosphataemia (adjusted OR 3.53, 95%CI 1.20-10.43). CONCLUSIONS The findings suggest that HDS are likely to be related to acute kidney injury rather than the progression of CKD in Thai patients with CKD. The products were associated with uncontrolled hyperphosphataemia. Patients who have CKD and use HDS should be closely monitored regarding their kidney function and electrolytes.
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Affiliation(s)
| | - Helen Boardman
- Division of Social Research in Medicines and Health, School of Pharmacy, University of Nottingham, Nottingham, UK
| | - Kearkiat Praditpornsilpa
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Dawn-Marie Walker
- Division of Primary Care, School of Medicine, University of Nottingham, Nottingham, UK
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Sakaguchi Y, Iwatani H, Hamano T, Tomida K, Kawabata H, Kusunoki Y, Shimomura A, Matsui I, Hayashi T, Tsubakihara Y, Isaka Y, Rakugi H. Magnesium modifies the association between serum phosphate and the risk of progression to end-stage kidney disease in patients with non-diabetic chronic kidney disease. Kidney Int 2015; 88:833-42. [PMID: 26061542 DOI: 10.1038/ki.2015.165] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 03/29/2015] [Accepted: 04/09/2015] [Indexed: 11/09/2022]
Abstract
It is known that magnesium antagonizes phosphate-induced apoptosis of vascular smooth muscle cells and prevents vascular calcification. Here we tested whether magnesium can also counteract other pathological conditions where phosphate toxicity is involved, such as progression of chronic kidney disease (CKD). We explored how the link between the risk of CKD progression and hyperphosphatemia is modified by magnesium status. A post hoc analysis was run in 311 non-diabetic CKD patients who were divided into four groups according to the median values of serum magnesium and phosphate. During a median follow-up of 44 months, 135 patients developed end-stage kidney disease (ESKD). After adjustment for relevant clinical factors, patients in the lower magnesium-higher phosphate group were at a 2.07-fold (95% CI: 1.23-3.48) risk for incident ESKD and had a significantly faster decline in estimated glomerular filtration rate compared with those in the higher magnesium-higher phosphate group. There were no significant differences in the risk of these renal outcomes among the higher magnesium-higher phosphate group and both lower phosphate groups. Incubation of tubular epithelial cells in high phosphate and low magnesium medium in vitro increased apoptosis and the expression levels of profibrotic and proinflammatory cytokine; these changes were significantly suppressed by increasing magnesium concentration. Thus, magnesium may act protectively against phosphate-induced kidney injury.
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Affiliation(s)
- Yusuke Sakaguchi
- Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Hirotsugu Iwatani
- Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takayuki Hamano
- Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kodo Tomida
- Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka, Japan
| | - Hiroaki Kawabata
- Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Yasuo Kusunoki
- Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Akihiro Shimomura
- Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Isao Matsui
- Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Terumasa Hayashi
- Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka, Japan
| | - Yoshiharu Tsubakihara
- Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Yoshitaka Isaka
- Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Hiromi Rakugi
- Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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Da J, Xie X, Wolf M, Disthabanchong S, Wang J, Zha Y, Lv J, Zhang L, Wang H. Serum Phosphorus and Progression of CKD and Mortality: A Meta-analysis of Cohort Studies. Am J Kidney Dis 2015; 66:258-65. [PMID: 25804679 DOI: 10.1053/j.ajkd.2015.01.009] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Accepted: 01/04/2015] [Indexed: 01/01/2023]
Abstract
BACKGROUND Recent studies have indicated that phosphorus may play an independent pathogenic role in chronic kidney disease (CKD) progression, but some of those studies were underpowered and yielded inconsistent results. STUDY DESIGN Systematic review and meta-analysis. SETTING & POPULATION Non-dialysis-dependent patients with CKD (transplant recipients were excluded). SELECTION CRITERIA FOR STUDIES Studies assessing the risk ratio of serum phosphorus level on kidney failure and mortality for non-dialysis-dependent patients with CKD published from January 1950 to June 2014 were included following systematic searching of MEDLINE, EMBASE, and the Cochrane Library. PREDICTOR Serum phosphorus level. OUTCOME Kidney failure, defined as doubled serum creatinine level, 50% decline in estimated glomerular filtration rate, or end-stage kidney disease. RESULTS In 12 cohort studies with 25,546 patients, 1,442 (8.8%) developed kidney failure and 3,089 (13.6%) died. Overall, every 1-mg/dL increase in serum phosphorus level was associated independently with increased risk of kidney failure (hazard ratio, 1.36; 95% CI, 1.20-1.55) and mortality (hazard ratio, 1.20; 95% CI, 1.05-1.37). LIMITATIONS Existence of potential residual confounding could not be excluded. CONCLUSIONS This meta-analysis suggests an independent association between serum phosphorus level and kidney failure and mortality among non-dialysis-dependent patients with CKD and suggests that large-scale randomized controlled trials should target disordered phosphorus homeostasis in CKD.
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Affiliation(s)
- Jingjing Da
- Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China; Renal Division, Department of Medicine, Guizhou Provincial People's Hospital; Guizhou Provincial Institute of Nephritic & Urinary Disease, Guiyang, Guizhou
| | - Xinfang Xie
- Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
| | - Myles Wolf
- Division of Nephrology and Hypertension, Department of Medicine, Division of Biostatistics, Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, FL
| | - Sinee Disthabanchong
- Division of Nephrology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Jinwei Wang
- Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
| | - Yan Zha
- Renal Division, Department of Medicine, Guizhou Provincial People's Hospital; Guizhou Provincial Institute of Nephritic & Urinary Disease, Guiyang, Guizhou
| | - Jicheng Lv
- Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
| | - Luxia Zhang
- Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
| | - Haiyan Wang
- Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
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Robinson-Cohen C, Hall YN, Katz R, Rivara MB, de Boer IH, Kestenbaum BR, Himmelfarb J. Self-rated health and adverse events in CKD. Clin J Am Soc Nephrol 2014; 9:2044-51. [PMID: 25301857 DOI: 10.2215/cjn.03140314] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND OBJECTIVES Little is known about the utility of self-rated general health assessments in persons with moderate-to-severe CKD. This study examined the ability of a single self-rated health measure to predict all-cause mortality and kidney disease progression in a cohort of 443 patients with stages 3-4 CKD, recruited between 2005 and 2011, and followed until the end of 2012. The performance of models incorporating self-rated health measures was compared with previously published predictive models and more complex models comprising a multibiomarker panel. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Participants were asked "In general, would you say your health is excellent, very good, good, fair, or poor?" Outcomes examined were time to all-cause mortality, kidney disease progression (initiation of RRT or 30% loss of eGFR), and a composite of these events. Model performances were compared using a nonparametric area under the curve (AUC) analysis. RESULTS Over a median follow-up of 3.3 years, 118 (27%) participants died and 138 (31%) had progression of kidney disease. Fair-to-poor self-rated health status was associated with significantly greater risks of mortality (fully adjusted hazard ratio [HR] for relative to good-to-excellent self-rated health, 2.76; 95% confidence interval [95% CI], 1.28 to 5.89), kidney disease progression (HR, 1.94; 95% CI, 1.49 to 2.56), and the combined end point (HR, 2.21; 95% CI, 1.66 to 2.96). For 3-year mortality prediction, the self-rated health model (AUC, 0.80; 95% CI, 0.76 to 0.85) had significantly higher AUCs than the base model (AUC, 0.71; 95% CI, 0.66 to 0.76) and the multibiomarker panel model (AUC, 0.74; 95% CI, 0.68 to 0.80) (P=0.03 and P=0.04, respectively). CONCLUSIONS A single, easily obtained measure of self-rated health helps identify patients with CKD at high risk of mortality and kidney disease progression. Routine evaluation of self-rated health may help target individuals who might benefit from more intensive monitoring strategies.
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Affiliation(s)
| | - Yoshio N Hall
- Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
| | | | - Matthew B Rivara
- Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
| | - Ian H de Boer
- Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
| | - Bryan R Kestenbaum
- Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
| | - Jonathan Himmelfarb
- Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
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Vo TM, Disthabanchong S. Are there ways to attenuate arterial calcification and improve cardiovascular outcomes in chronic kidney disease? World J Cardiol 2014; 6:216-226. [PMID: 24944752 PMCID: PMC4062121 DOI: 10.4330/wjc.v6.i5.216] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 04/18/2014] [Accepted: 04/19/2014] [Indexed: 02/06/2023] Open
Abstract
The risk of cardiovascular mortality among patients with end-stage renal disease is several times higher than general population. Arterial calcification, a marker of atherosclerosis and a predictor of cardiovascular mortality, is common in chronic kidney disease (CKD). The presence of traditional cardiovascular risk factors such as diabetes, hypertension, hyperlipidemia, and advanced age cannot fully explain the high prevalence of atherosclerosis and arterial calcification. Other factors specific to CKD such as hyperphosphatemia, excess of calcium, high dose active vitamin D and prolonged dialysis vintage play important roles in the development of arterial calcification. Due to the significant health risk, it is prudent to attempt to lower arterial calcification burden in CKD. Treatment of hyperlipidemia with statin has failed to lower atherosclerotic and arterial calcification burden. Data on diabetes and blood pressure controls as well as smoking cessation on cardiovascular outcomes in CKD population are limited. Currently available treatment options include non-calcium containing phosphate binders, low dose active vitamin D, calcimimetic agent and perhaps bisphosphonates, vitamin K and sodium thiosulfate. Preliminary data on bisphosphonates, vitamin K and sodium thiosulfate are encouraging but larger studies on efficacy and outcomes are needed.
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Disthabanchong S, Jongjirasiri S, Adirekkiat S, Sumethkul V, Ingsathit A, Domrongkitchaiporn S, Phakdeekitcharoen B, Kantachuvesiri S, Kitiyakara C. Low hip bone mineral density predicts mortality in maintenance hemodialysis patients: a five-year follow-up study. Blood Purif 2014; 37:33-8. [PMID: 24503711 DOI: 10.1159/000357639] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2013] [Accepted: 11/26/2013] [Indexed: 02/05/2023]
Abstract
BACKGROUND Bone loss is common among hemodialysis patients and contributes to mortality. The association between bone loss and vascular calcification may explain the increased mortality risk. Studies on the association between decreased bone mass and mortality in maintenance hemodialysis patients are limited. METHODS Eighty-three hemodialysis patients underwent bone mineral density (BMD) and coronary artery calcification (CAC) measurements. The relationship between BMD and mortality was analyzed after a 5-year follow-up period. RESULTS Eighty percent of the patients had reduced hip BMD. In univariate Cox regression analyses, age, cardiovascular disease, dyslipidemia, increased CAC score, increased comorbidity score and decreased hip BMD were associated with mortality. Low hip BMD remained independently associated with mortality after adjustments for cardiovascular risk factors, comorbidity score and CAC score. Patients with BMD in the lowest tertile had the worst survival. CONCLUSION Low hip BMD predicted mortality in maintenance hemodialysis patients independent of CAC.
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Affiliation(s)
- Sinee Disthabanchong
- Division of Nephrology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Disthabanchong S. Lowering vascular calcification burden in chronic kidney disease: Is it possible? World J Nephrol 2013; 2:49-55. [PMID: 24255887 PMCID: PMC3832912 DOI: 10.5527/wjn.v2.i3.49] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 05/21/2013] [Accepted: 07/18/2013] [Indexed: 02/06/2023] Open
Abstract
High prevalence of atherosclerosis and arterial calcification in chronic kidney disease is far beyond the explanation by common cardiovascular risk factors such as aging diabetes, hypertension and dyslipidemia. The magnitude of coronary artery calcification is independently and inversely associated with renal function. In addition to cardiovascular risk factors, other chronic kidney disease-related risks such as phosphate retention, excess of calcium and prolonged dialysis vintage also contribute to the development of vascular calcification. Strategies to lower vascular calcification burden in chronic kidney disease population should include minimizing chronic kidney disease and atherosclerotic risk factors. Current therapies available are non-calcium containing phosphate binders, low dose active vitamin D and calcimimetic agent. The role of bisphosphonates in vascular calcification in chronic kidney disease population remains unclear. Preliminary data on sodium thiosulfate are promising, however, larger studies on efficacy and patient outcomes are necessary. Several large randomized controlled trials have confirmed the lack of benefit of statin in attenuating the progression of vascular calcification.
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