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1
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Su D, Zhang X, He K, Chen Y, Wu N. Individualized prediction of chronic kidney disease for the elderly in longevity areas in China: Machine learning approaches. Front Public Health 2022; 10:998549. [PMID: 36339144 PMCID: PMC9634246 DOI: 10.3389/fpubh.2022.998549] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 09/20/2022] [Indexed: 01/26/2023] Open
Abstract
Background Chronic kidney disease (CKD) has become a major public health problem worldwide and has caused a huge social and economic burden, especially in developing countries. No previous study has used machine learning (ML) methods combined with longitudinal data to predict the risk of CKD development in 2 years amongst the elderly in China. Methods This study was based on the panel data of 925 elderly individuals in the 2012 baseline survey and 2014 follow-up survey of the Healthy Aging and Biomarkers Cohort Study (HABCS) database. Six ML models, logistic regression (LR), lasso regression, random forests (RF), gradient-boosted decision tree (GBDT), support vector machine (SVM), and deep neural network (DNN), were developed to predict the probability of CKD amongst the elderly in 2 years (the year of 2014). The decision curve analysis (DCA) provided a range of threshold probability of the outcome and the net benefit of each ML model. Results Amongst the 925 elderly in the HABCS 2014 survey, 289 (18.8%) had CKD. Compared with the other models, LR, lasso regression, RF, GBDT, and DNN had no statistical significance of the area under the receiver operating curve (AUC) value (>0.7), and SVM exhibited the lowest predictive performance (AUC = 0.633, p-value = 0.057). DNN had the highest positive predictive value (PPV) (0.328), whereas LR had the lowest (0.287). DCA results indicated that within the threshold ranges of ~0-0.03 and 0.37-0.40, the net benefit of GBDT was the largest. Within the threshold ranges of ~0.03-0.10 and 0.26-0.30, the net benefit of RF was the largest. Age was the most important predictor variable in the RF and GBDT models. Blood urea nitrogen, serum albumin, uric acid, body mass index (BMI), marital status, activities of daily living (ADL)/instrumental activities of daily living (IADL) and gender were crucial in predicting CKD in the elderly. Conclusion The ML model could successfully capture the linear and nonlinear relationships of risk factors for CKD in the elderly. The decision support system based on the predictive model in this research can help medical staff detect and intervene in the health of the elderly early.
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Affiliation(s)
- Dai Su
- Department of Health Management and Policy, School of Public Health, Capital Medical University, Beijing, China
| | - Xingyu Zhang
- Department of Systems, Populations, and Leadership, University of Michigan School of Nursing, Ann Arbor, MI, United States,Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Kevin He
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, United States
| | - Yingchun Chen
- Department of Health Management, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,Research Center for Rural Health Services, Hubei Province Key Research Institute of Humanities and Social Sciences, Wuhan, China
| | - Nina Wu
- Department of Health Management and Policy, School of Public Health, Capital Medical University, Beijing, China,*Correspondence: Nina Wu
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Lorenzo JPP, Sollano MHMZ, Salido EO, Li-Yu J, Tankeh-Torres SA, Wulansari Manuaba IAR, Rahman MM, Paul BJ, Mok MY, De Silva M, Padhan P, Lim AL, Marcial M, Vicera JJ, Haq SA, Salman S, Liyanage CK, Keen HI, Yew Kuang C, Wei JCC, Hellmi RY, Chan CE, Louthrenoo W. 2021 Asia-Pacific League of Associations for Rheumatology clinical practice guideline for treatment of gout. Int J Rheum Dis 2021; 25:7-20. [PMID: 34931463 DOI: 10.1111/1756-185x.14266] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 11/30/2021] [Accepted: 12/03/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Gout is the most prevalent inflammatory arthritis in the Asia-Pacific region and worldwide. This clinical practice guideline (CPG) aims to provide recommendations based on systematically obtained evidence and values and preferences tailored to the unique needs of patients with gout and hyperuricemia in Asia, Australasia, and the Middle East. The target users of these guidelines are general practitioners and specialists, including rheumatologists, in these regions. METHODS Relevant clinical questions were formulated by the Steering Committee. Systematic reviews of evidence were done, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation methodology. A multi-sectoral consensus panel formulated the final recommendations. RESULTS The Asia-Pacific League of Associations for Rheumatology Task Force developed this CPG for treatment of gout with 3 overarching principles and 22 recommendation statements that covered the treatment of asymptomatic hyperuricemia (2 statements), treatment of acute gout (4 statements), prophylaxis against gout flare when initiating urate-lowering therapy (3 statements), urate-lowering therapy (3 statements), treatment of chronic tophaceous gout (2 statements), treatment of complicated gout and non-responders (2 statements), treatment of gout with moderate to severe renal impairment (1 statement), and non-pharmacologic interventions (5 statements). CONCLUSION Recommendations for clinically relevant scenarios in the management of gout were formulated to guide physicians in administering individualized care.
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Affiliation(s)
| | | | - Evelyn O Salido
- College of Medicine, University of the Philippines Manila, Manila, Philippines
| | - Julie Li-Yu
- University of Santo Tomas, Manila, Philippines
| | | | | | | | | | - Mo Yin Mok
- Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong
| | | | - Prasanta Padhan
- Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, India
| | | | | | | | - Syed Atiqul Haq
- Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Sami Salman
- Department of Medicine, College of Medicine, University of Baghdad, Baghdad, Iraq
| | - Chiranthi K Liyanage
- Department of Pharmacology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Helen I Keen
- University of Western and Perth, Perth, WA, Australia.,Murdoch University, Perth, WA, Australia
| | - Cheng Yew Kuang
- Farrer Park Medical Center, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | | | - Rakhma Yanti Hellmi
- Rheumatology Division, Dr Kariadi General Hospital Medical Center, Diponegoro University, Semarang, Indonesia
| | | | - Worawit Louthrenoo
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Sharma G, Dubey A, Nolkha N, Singh JA. Hyperuricemia, urate-lowering therapy, and kidney outcomes: a systematic review and meta-analysis. Ther Adv Musculoskelet Dis 2021; 13:1759720X211016661. [PMID: 34104231 PMCID: PMC8161880 DOI: 10.1177/1759720x211016661] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 01/03/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Contradictory evidence exists for association of hyperuricemia and kidney function. To investigate the association of hyperuricemia and kidney function decline (hyperuricemia question) and effect of urate-lowering therapies (ULTs) on kidney function (ULT question), we performed a systematic review and meta-analysis. METHODS MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from inception to July 2020. We selected observational studies for the hyperuricemia question and controlled trials for the ULT question. Two investigators independently assessed study eligibility and abstracted the data. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane risk of bias tool. Meta-analysis was done using the inverse variance method and random effect model. We estimated odds ratio (OR), hazard ratio (HR), risk ratio (RR), and the mean difference (MD). Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS Of 12,037 studies screened, 131 studies with 3,414,226 patients were included. Hyperuricemia was associated with a significant risk of rapid estimated glomerula filtration rate (eGFR) decline ⩾3 ml/min per 1.73 m2 per year (OR 1.38, 95% CI 1.20-1.59; low certainty), albuminuria (OR/HR 1.94, 95% CI 1.34-2.79; very low certainty), chronic kidney disease (OR/HR 2.13, 95% CI 1.74-2.61; very low certainty), and kidney failure (HR 1.53, 95% CI 1.18-1.99; very low certainty). Compared with control, ULT use for ⩾1 year was associated with significantly more improved eGFR (MD 1.81 ml/min per 1.73 m2, 95% CI 0.26-3.35; very low certainty), serum creatinine (MD -0.33 mg/dl, 95% CI -0.47 to -0.19; low certainty), and proteinuria (MD -5.44 mg/day, 95% CI -8.49 to -2.39; low certainty), but no difference in kidney failure. CONCLUSION Hyperuricemia is associated with worsening eGFR, albuminuria, chronic kidney disease, and kidney failure. ULT use for ⩾1 year may improve kidney function. REGISTRATION The protocol was registered at PROSPERO database, CRD42015013859.
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Affiliation(s)
- Gaurav Sharma
- Department of Internal Medicine, University of South Alabama, Mobile, AL, USA
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, AL, USA
- Department of Internal Medicine, Seth GS Medical College and KEM Hospital, Mumbai, MH, India
| | - Abhishek Dubey
- Department of Internal Medicine, Seth GS Medical College and KEM Hospital, Mumbai, MH, India
| | - Nilesh Nolkha
- Department of Rheumatology, Cannock Chase Hospital, Cannock, UK
| | - Jasvinder A. Singh
- Division of Clinical Immunology and Rheumatology, Department of Medicine at the School of Medicine and the Department of Epidemiology at the School of Public Health, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S., Birmingham, AL 35294-0022, USA
- Medicine Service, VA Medical Center, Birmingham, AL 35233, USA
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Petreski T, Ekart R, Hojs R, Bevc S. Hyperuricemia, the heart, and the kidneys - to treat or not to treat? Ren Fail 2020; 42:978-986. [PMID: 32972284 PMCID: PMC7534372 DOI: 10.1080/0886022x.2020.1822185] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 08/25/2020] [Accepted: 09/06/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hyperuricemia is a state in which the serum levels of uric acid are elevated. As such it has a pronounced effect on vascular and renal function with their consequences, while also showing some antioxidant effects that show to be beneficial. SUMMARY Hyperuricemia has shown to have a J-shaped relationship with mortality, is frequently associated with development and progression of heart and kidney disease, and is correlated with malnutrition-inflammation-atherosclerosis syndrome, although several Mendelian studies have failed to show an association with morbidity and mortality. Hyperuricemia is usually associated with gout flares and tophi development but can also present as asymptomatic hyperuricemia. It is still uncertain whether asymptomatic hyperuricemia is an independent risk factor for cardiovascular or renal disease and as such its treatment is questionable. KEY MESSAGES Some possible tools for future decision making are the use of noninvasive techniques such as pulse wave analysis, urinary sediment analysis, and joint ultrasound, which could help identify individuals with asymptomatic hyperuricemia that could benefit from urate lowering therapy most.
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Affiliation(s)
- Tadej Petreski
- Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
| | - Robert Ekart
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
- Department of Dialysis, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia
| | - Radovan Hojs
- Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
| | - Sebastjan Bevc
- Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
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5
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Abstract
OBJECTIVE Hyperuricemia has been epidemiologically associated with multiple comorbidities including chronic renal failure and cardiovascular disease. Cause and effect are difficult to address, given comorbidities associated with and prevalence of metabolic syndrome. One impediment to achieving serum uric acid (sUa) levels less than or equal to 6.0 mg/DL is the concept that allopurinol might be nephrotoxic. We examined the relation of sUa less than or equal to 6.0 mg/dL to renal function over time. METHODS This is a medical records review study of 348 hyperuricemia patients identified in 2015, as having been followed with serial uric acid measurements. After 1 year of serial urate levels, to allow for treatment, patient cohorts were defined: sUa less than or equal to 6.0 mg/dL and sUa greater than 6.0 mg/dL. A repeated measure model was used to test for an association between uric acid level and serum creatinine, while adjusting for covariates. RESULTS There was a significant difference in the least square means of serum creatinine comparing those who achieved an sUa less than or equal to 6.0 mg/dL versus sUa greater than 6.0 mg/dL (1.39 mg/dL [95% confidence interval, 1.30-1.48] vs 1.57 mg/dL [95% confidence interval, 1.46-1.69]; p = 0.0015). This is a between-group difference in creatinine of 0.18 mg/dL. If a change in serum creatinine of 0.2 is considered significant, this short-term between-group progression of renal failure approaches clinical significance. CONCLUSIONS Given that most serial measures were within the first few years of follow-up, and change in renal function occurs slowly over time, the between group difference of sUa of 0.18 mg/dL is close to a clinically significant creatinine difference of 0.2 mg/dL.
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6
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Chou HW, Chiu HT, Tsai CW, Ting IW, Yeh HC, Huang HC, Kuo CC. Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study. Nephrol Dial Transplant 2019; 33:1620-1627. [PMID: 29165620 DOI: 10.1093/ndt/gfx313] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Accepted: 10/04/2017] [Indexed: 12/21/2022] Open
Abstract
Background Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis. A total of 874 patients with hyperuricemia who were newly treated with allopurinol, febuxostat or benzbromarone were included. The primary and secondary outcomes were incident end-stage renal disease (ESRD) and the serum uric acid (SUA) changes from baseline, respectively. The results were analyzed using multiple Cox proportional models adjusted for multinomial propensity scores. For subgroup analyses, we further stratified patients according to whether their latest SUA level reached the therapeutic target. Results Compared with allopurinol, benzbromarone therapy was associated with a reduced risk of progression to dialysis, the adjusted hazard ratio was 0.50 (95% confidence interval, 0.25-0.99). Patients who received allopurinol or febuxostat exhibited a comparable risk of ESRD [adjusted hazard ratio, 0.99 (0.40-2.44)]. Febuxostat was significantly more potent than allopurinol or benzbromarone in lowering SUA levels in the fully adjusted model. Among patients who reached the therapeutic target, those with febuxostat and benzbromarone initiation had a significantly lower risk of ESRD. Conclusions In conclusion, compared with conventional allopurinol, febuxostat and benzbromarone may be more effective in reducing the risk of progression to dialysis and in lowering SUA levels in CKD populations.
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Affiliation(s)
- Hsu-Wen Chou
- Clinical Research Outcome and Training Center, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Hsien-Tsai Chiu
- Clinical Research Outcome and Training Center, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Ching-Wei Tsai
- Department of Internal Medicine, Kidney Institute and Division of Nephrology, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan.,Big Data Center, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - I-Wen Ting
- Department of Internal Medicine, Kidney Institute and Division of Nephrology, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan
| | - Hung-Chieh Yeh
- Department of Internal Medicine, Kidney Institute and Division of Nephrology, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan
| | - Han-Chun Huang
- Clinical Research Outcome and Training Center, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Chin-Chi Kuo
- Department of Internal Medicine, Kidney Institute and Division of Nephrology, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan.,Big Data Center, China Medical University Hospital, China Medical University, Taichung, Taiwan
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7
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Sato Y, Feig DI, Stack AG, Kang DH, Lanaspa MA, Ejaz AA, Sánchez-Lozada LG, Kuwabara M, Borghi C, Johnson RJ. The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD. Nat Rev Nephrol 2019; 15:767-775. [PMID: 31296965 DOI: 10.1038/s41581-019-0174-z] [Citation(s) in RCA: 122] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/12/2019] [Indexed: 02/07/2023]
Abstract
Hyperuricaemia is common among patients with chronic kidney disease (CKD), and increases in severity with the deterioration of kidney function. Although existing guidelines for CKD management do not recommend testing for or treatment of hyperuricaemia in the absence of a diagnosis of gout or urate nephrolithiasis, an emerging body of evidence supports a direct causal relationship between serum urate levels and the development of CKD. Here, we review randomized clinical trials that have evaluated the effect of urate-lowering therapy (ULT) on the rate of CKD progression. Among trials in which individuals in the control arm experienced progressive deterioration of kidney function (which we define as ≥4 ml/min/1.73 m² over the course of the study - typically 6 months to 2 years), treatment with ULT conferred consistent clinical benefits. In contrast, among trials where clinical progression was not observed in the control arm, treatment with ULT was ineffective, but this finding should not be used as an argument against the use of uric acid-lowering therapy. Although additional studies are needed to identify threshold values of serum urate for treatment initiation and to confirm optimal target levels, we believe that sufficient evidence exists to recommend routine measurement of serum urate levels in patients with CKD and consider initiation of ULT among those who are hyperuricaemic with evidence of deteriorating renal function, unless specific contraindications exist.
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Affiliation(s)
- Yuka Sato
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Daniel I Feig
- Division of Pediatric Nephrology, University of Alabama, Birmingham, AL, USA
| | - Austin G Stack
- Division of Nephrology, Department of Medicine, University Hospital Limerick, Limerick, Ireland.,Graduate Entry Medical School, University of Limerick, Limerick, Ireland
| | - Duk-Hee Kang
- Division of Nephrology, Department of Internal Medicine, Ewha Womans University College of Medicine Ewha Medical Research Center, Seoul, South Korea
| | - Miguel A Lanaspa
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - A Ahsan Ejaz
- Division of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, FL, USA
| | - L Gabriela Sánchez-Lozada
- Laboratory of Renal Physiopathology, Department of Nephrology, INC Ignacio Chavez, Mexico City, Mexico
| | - Masanari Kuwabara
- Department of Cardiology and Intensive Care Unit, Toranomon Hospital, Tokyo, Japan
| | - Claudio Borghi
- Department of Medicine, University of Bologna, Bologna, Italy
| | - Richard J Johnson
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. .,Rocky Mountain Regional VA Medical Center, Aurora, CO, USA.
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Karnthaler-Benbakka C, Koblmüller B, Mathuber M, Holste K, Berger W, Heffeter P, Kowol CR, Keppler BK. Synthesis, Characterization and in vitro Studies of a Cathepsin B-Cleavable Prodrug of the VEGFR Inhibitor Sunitinib. Chem Biodivers 2018; 16:e1800520. [PMID: 30566287 PMCID: PMC6391952 DOI: 10.1002/cbdv.201800520] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 11/15/2018] [Indexed: 01/08/2023]
Abstract
Since several decades, the prodrug concept has raised considerable interest in cancer research due to its potential to overcome common problems associated with chemotherapy. However, for small‐molecule tyrosine kinase inhibitors, which also cause severe side effects, hardly any strategies to generate prodrugs for therapeutic improvement have been reported so far. Here, we present the synthesis and biological investigation of a cathepsin B‐cleavable prodrug of the VEGFR inhibitor sunitinib. Cell viability assays and Western blot analyses revealed, that, in contrast to the non‐cathepsin B‐cleavable reference compound, the prodrug shows activity comparable to the original drug sunitinib in the highly cathepsin B‐expressing cell lines Caki‐1 and RU‐MH. Moreover, a cathepsin B cleavage assay confirmed the desired enzymatic activation of the prodrug. Together, the obtained data show that the concept of cathepsin B‐cleavable prodrugs can be transferred to the class of targeted therapeutics, allowing the development of optimized tyrosine kinase inhibitors for the treatment of cancer.
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Affiliation(s)
- Claudia Karnthaler-Benbakka
- Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 42, AT-1090, Wien
| | - Bettina Koblmüller
- Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8 A, AT-1090, Wien
| | - Marlene Mathuber
- Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 42, AT-1090, Wien
| | - Katharina Holste
- Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8 A, AT-1090, Wien
| | - Walter Berger
- Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8 A, AT-1090, Wien.,Research Cluster 'Translational Cancer Therapy Research', University of Vienna and Medical University of Vienna, AT-1090, Wien
| | - Petra Heffeter
- Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8 A, AT-1090, Wien.,Research Cluster 'Translational Cancer Therapy Research', University of Vienna and Medical University of Vienna, AT-1090, Wien
| | - Christian R Kowol
- Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 42, AT-1090, Wien.,Research Cluster 'Translational Cancer Therapy Research', University of Vienna and Medical University of Vienna, AT-1090, Wien
| | - Bernhard K Keppler
- Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 42, AT-1090, Wien.,Research Cluster 'Translational Cancer Therapy Research', University of Vienna and Medical University of Vienna, AT-1090, Wien
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9
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Li X, Meng X, Spiliopoulou A, Timofeeva M, Wei WQ, Gifford A, Shen X, He Y, Varley T, McKeigue P, Tzoulaki I, Wright AF, Joshi P, Denny JC, Campbell H, Theodoratou E. MR-PheWAS: exploring the causal effect of SUA level on multiple disease outcomes by using genetic instruments in UK Biobank. Ann Rheum Dis 2018; 77:1039-1047. [PMID: 29437585 PMCID: PMC6029646 DOI: 10.1136/annrheumdis-2017-212534] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 01/12/2018] [Accepted: 01/21/2018] [Indexed: 02/05/2023]
Abstract
OBJECTIVES We aimed to investigate the role of serum uric acid (SUA) level in a broad spectrum of disease outcomes using data for 120 091 individuals from UK Biobank. METHODS We performed a phenome-wide association study (PheWAS) to identify disease outcomes associated with SUA genetic risk loci. We then implemented conventional Mendelianrandomisation (MR) analysis to investigate the causal relevance between SUA level and disease outcomes identified from PheWAS. We next applied MR Egger analysis to detect and account for potential pleiotropy, which conventional MR analysis might mistake for causality, and used the HEIDI (heterogeneity in dependent instruments) test to remove cross-phenotype associations that were likely due to genetic linkage. RESULTS Our PheWAS identified 25 disease groups/outcomes associated with SUA genetic risk loci after multiple testing correction (P<8.57e-05). Our conventional MR analysis implicated a causal role of SUA level in three disease groups: inflammatory polyarthropathies (OR=1.22, 95% CI 1.11 to 1.34), hypertensive disease (OR=1.08, 95% CI 1.03 to 1.14) and disorders of metabolism (OR=1.07, 95% CI 1.01 to 1.14); and four disease outcomes: gout (OR=4.88, 95% CI 3.91 to 6.09), essential hypertension (OR=1.08, 95% CI 1.03 to 1.14), myocardial infarction (OR=1.16, 95% CI 1.03 to 1.30) and coeliac disease (OR=1.41, 95% CI 1.05 to 1.89). After balancing pleiotropic effects in MR Egger analysis, only gout and its encompassing disease group of inflammatory polyarthropathies were considered to be causally associated with SUA level. Our analysis highlighted a locus (ATXN2/S2HB3) that may influence SUA level and multiple cardiovascular and autoimmune diseases via pleiotropy. CONCLUSIONS Elevated SUA level is convincing to cause gout and inflammatory polyarthropathies, and might act as a marker for the wider range of diseases with which it associates. Our findings support further investigation on the clinical relevance of SUA level with cardiovascular, metabolic, autoimmune and respiratory diseases.
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Affiliation(s)
- Xue Li
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Xiangrui Meng
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Athina Spiliopoulou
- Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Maria Timofeeva
- Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Wei-Qi Wei
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Aliya Gifford
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Xia Shen
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Yazhou He
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
- West China School of Medicine, West China Hospital, Sichuan University, Sichuan, China
| | - Tim Varley
- Public Health and Intelligence, NHS National Services Scotland, Edinburgh, UK
| | - Paul McKeigue
- Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Ioanna Tzoulaki
- Department Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- MRC-PHE Centre for Environment, School of Public Health, Imperial College London, London, UK
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
| | - Alan F Wright
- Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Peter Joshi
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Joshua C Denny
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Harry Campbell
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Evropi Theodoratou
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
- Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
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Su X, Xu B, Yan B, Qiao X, Wang L. Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis. PLoS One 2017; 12:e0187550. [PMID: 29095953 PMCID: PMC5667873 DOI: 10.1371/journal.pone.0187550] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 10/20/2017] [Indexed: 02/03/2023] Open
Abstract
Background and objectives The effects of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of uric acid-lowering agents on major clinical outcomes of CKD. Design, setting, participants, and measurements According to the pre-specified protocol that was registered with PROSPERO (No. CRD42016038030), we searched systematically in MEDLINE, EMBASE, and the Cochrane Library for trials up to February 2016. Prospective, randomized, controlled trials assessing the effects of uric acid-lowering agents on cardiovascular and kidney outcomes in patients with CKD were included. Random-effects analytical methods were used. Results Sixteen eligible trials were identified, providing data for 1,211 patients with CKD, including 146 kidney failure events and 69 cardiovascular events. Uric acid-lowering therapy produced a 55% relative risk (RR) reduction (95% confidence interval [95% CI], 31–64) for kidney failure events (P < 0.001), and a 60% RR reduction (95% CI, 17–62) for cardiovascular events (P < 0.001), but had no significant effect on the risk of all-cause death (RR, 0.86; 95% CI, 0.50–1.46). The mean differences in rate of decline in the estimated glomerular filtration rate (4.10 mL/min/1.73 m2 per year slower in uric acid-lowering therapy recipients, 95% CI, 1.86–6.35) and the standardized mean differences in the change in proteinuria or albuminuria (−0.23 units of standard deviation greater in uric acid-lowering therapy recipients; 95% CI, −0.43 to −0.04) were also statistically significant. Conclusions Uric acid-lowering therapy seemed to improve kidney outcomes and reduce the risk of cardiovascular events in adults with CKD.
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Affiliation(s)
- Xiaole Su
- Renal Division, Shanxi Medical University Second Hospital, Taiyuan, Shanxi, China
| | - Boyang Xu
- Renal Division, Shanxi Medical University Second Hospital, Taiyuan, Shanxi, China
| | - Bingjuan Yan
- Renal Division, Shanxi Medical University Second Hospital, Taiyuan, Shanxi, China
| | - Xi Qiao
- Renal Division, Shanxi Medical University Second Hospital, Taiyuan, Shanxi, China
| | - Lihua Wang
- Renal Division, Shanxi Medical University Second Hospital, Taiyuan, Shanxi, China
- * E-mail:
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11
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Chini L, Assis L, Lugon J. Relationship between uric acid levels and risk of chronic kidney disease in a retrospective cohort of Brazilian workers. Braz J Med Biol Res 2017; 50:e6048. [PMID: 28793050 PMCID: PMC5572852 DOI: 10.1590/1414-431x20176048] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 05/31/2017] [Indexed: 01/01/2023] Open
Abstract
Uric acid (UA) levels are increased in patients with kidney dysfunction. We analyzed the association between asymptomatic hyperuricemia and new-onset chronic kidney disease (CKD). A retrospective cohort study was designed to collect data from employees of an energy generation and distribution company in the city of Rio de Janeiro, Brazil, who had undergone the company's annual medical checkup from 2008 to 2014. People with ≤2 years of follow-up, with baseline estimated glomerular filtration rate (eGFR) <60 mL·min-1·(1.73 m2)-1 or with incomplete data were excluded. The endpoint was defined as eGFR <60 mL·min-1·(1.73 m2)-1 estimated through the chronic kidney disease epidemiology collaboration equation (CKD-EPI). The study included 1094 participants. The mean follow-up period was 5.05±1.05 years and 44 participants exhibited new-onset CKD. The prevalence of hyperuricemia was 4.2%. There was a significant inverse correlation between baseline serum levels of UA and baseline eGFR (R=-0.21, P<0.001). Female gender (OR=4.00; 95%CI=1.92-8.29, P<0.001) and age (OR=1.06; 95%CI=1.02-1.11, P=0.004) but not UA levels (OR=1.12; 95%CI=0.83-1.50; P=0.465) were associated with new-onset CKD. Diabetes mellitus and body mass index were independent factors for fast progression (OR=2.17; 95%CI=1.24-3.80, P=0.007 and OR=1.04; 95%CI=1.01-1.07; P=0.020). These results did not support UA as an independent predictor for CKD progression in the studied population.
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Affiliation(s)
- L.S.N. Chini
- Divisão de Medicina Interna, Departamento de Medicina, Universidade Federal Fluminense, Niterói, RJ, Brasil
| | - L.I.S. Assis
- Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - J.R. Lugon
- Divisão de Nefrologia, Departamento de Medicina, Universidade Federal Fluminense, Niterói, RJ, Brasil
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12
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Li X, Meng X, Timofeeva M, Tzoulaki I, Tsilidis KK, Ioannidis JPA, Campbell H, Theodoratou E. Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies. BMJ 2017; 357:j2376. [PMID: 28592419 PMCID: PMC5461476 DOI: 10.1136/bmj.j2376] [Citation(s) in RCA: 234] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/10/2017] [Indexed: 01/05/2023]
Abstract
Objective To map the diverse health outcomes associated with serum uric acid (SUA) levels.Design Umbrella review.Data sources Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references.Eligibility criteria Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes.Results 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10-6, 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies.Conclusion Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis.
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Affiliation(s)
- Xue Li
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK
| | - Xiangrui Meng
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK
| | - Maria Timofeeva
- Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Ioanna Tzoulaki
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Konstantinos K Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - John PA Ioannidis
- Stanford Prevention Research Center, Stanford School of Medicine, Stanford, CA, USA
- Department of Health Research and Policy, Stanford School of Medicine, Stanford, CA, USA
- Department of Statistics, Stanford University, Stanford, CA, USA
| | - Harry Campbell
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK
| | - Evropi Theodoratou
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK
- Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK
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13
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Smolen LJ, Gahn JC, Mitri G, Shiozawa A. The Budget Impact of Increased Use of Febuxostat in the Management of Gout: A US Health Plan Managed Care Pharmacy and Medical Costs Perspective. Clin Ther 2016; 38:1710-25. [PMID: 27269247 DOI: 10.1016/j.clinthera.2016.05.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Revised: 05/06/2016] [Accepted: 05/11/2016] [Indexed: 12/22/2022]
Abstract
PURPOSE Gout is a chronic disease characterized by the deposition of urate crystals in the joints and throughout the body, caused by an excess burden of serum uric acid (sUA). The study estimates pharmacy and medical cost budgetary impacts of wider adoption by US payers of febuxostat, a urate-lowering therapy (ULT) for the treatment of gout. METHODS A US payer-perspective budget impact model followed ULT patients from a 1,000,000-member plan over 3 years. The current market share scenario, febuxostat (6%) and ULT allopurinol (94%), was compared with an 18% febuxostat market share. Data were implemented from randomized controlled trials, census and epidemiologic studies, and real-world database analyses. An innovation was the inclusion of gout-related chronic kidney disease costs. Cost results were estimated as annual and cumulative incremental costs, expressed as total costs, cost per member per month, and cost per treated member per month. Clinical results were also estimated. FINDINGS Increasing the febuxostat market share resulted in a 6.3% increase in patients achieving the sUA target level of <6.0 mg/dL and a 1.4% reduction in gout flares during the 3-year period. Total cost increased 1.4%, with a 49.9% increase in ULT costs, a 1.4% reduction in flare costs, a 1.2% reduction in chronic kidney disease costs, and a 2.8% reduction in gout care costs. The cumulative incremental costs were $1,307,425 in the first year, $1,939,016 through the second year, and $2,092,744 through the third year. By the third year, savings in medical costs offset most of the increase in treatment costs. Impacts on cumulative cost per member per month and cumulative cost per treated member per month followed the same pattern, with the highest impact in the first year and cumulative impacts declining during the 3-year period. The cumulative cost per member per month impact was estimated as $0.109, $0.081, and $0.058 and the cumulative cost per treated member per month impact was estimated as $12.416, $9.207, and $6.625 in the first year, through the second year, and through the third year, respectively. IMPLICATIONS Expanding the febuxostat market share would result in improved clinical outcomes, but with an overall increase in costs over 3 years due to higher costs of treatment. By the third year, savings in medical costs, primarily in chronic kidney disease costs, would offset most of the increase in treatment costs. Expanded use of febuxostat in the treatment of all gout patients, independent of renal impairment status, should be considered based on improved clinical outcomes and longer-term medical cost savings associated with these improved outcomes.
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Affiliation(s)
- Lee J Smolen
- Medical Decision Modeling Inc, Indianapolis, Indiana.
| | - James C Gahn
- Medical Decision Modeling Inc, Indianapolis, Indiana
| | - Ghaith Mitri
- Takeda Pharmaceuticals International, Inc., Deerfield, Illinois
| | - Aki Shiozawa
- Takeda Pharmaceuticals International, Inc., Deerfield, Illinois
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14
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Qin T, Zhou X, Wang J, Wu X, Li Y, Wang L, Huang H, Li J. Hyperuricemia and the Prognosis of Hypertensive Patients: A Systematic Review and Meta-Analysis. J Clin Hypertens (Greenwich) 2016; 18:1268-1278. [PMID: 27247021 DOI: 10.1111/jch.12855] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2016] [Revised: 02/25/2016] [Accepted: 03/12/2016] [Indexed: 02/05/2023]
Affiliation(s)
- Tianqiang Qin
- Department of Evidence-Based Medicine and Clinical Epidemiology; West China Hospital; Sichuan University; Chengdu China
| | - Xiaoqin Zhou
- Department of Evidence-Based Medicine and Clinical Epidemiology; West China Hospital; Sichuan University; Chengdu China
| | - Ji Wang
- Department of Evidence-Based Medicine and Clinical Epidemiology; West China Hospital; Sichuan University; Chengdu China
| | - Xinyu Wu
- Department of Evidence-Based Medicine and Clinical Epidemiology; West China Hospital; Sichuan University; Chengdu China
| | - Yulin Li
- Second Affiliated Hospital of Chengdu University of TCM; Chengdu University of TCM; Chengdu China
| | - Ling Wang
- Department of Cardiology; Mianyang People's Hospital; Mianyang City China
| | - He Huang
- Department of Cardiology; West China Hospital; Sichuan University; Chengdu China
| | - Jing Li
- Department of Evidence-Based Medicine and Clinical Epidemiology; West China Hospital; Sichuan University; Chengdu China
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15
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Mome R, Bakinde N. Febuxostat for Asymptomatic Hyperuricemia in CKD. Am J Kidney Dis 2016; 67:989. [PMID: 27211367 DOI: 10.1053/j.ajkd.2015.09.035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Accepted: 09/15/2015] [Indexed: 01/02/2023]
Affiliation(s)
- Ruth Mome
- Morehouse School of Medicine, Atlanta, Georgia
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Abstract
OBJECTIVE To determine the cost-effectiveness of febuxostat vs allopurinol for the management of gout. METHODS A stochastic microsimulation cost-effectiveness model with a US private-payer perspective and 5-year time horizon was developed. Model flow based on guideline and real-world treatment paradigms incorporated gout flare, serum uric acid (sUA) testing, treatment titration, discontinuation, and adverse events, chronic kidney disease (CKD) incidence and progression, and type 2 diabetes mellitus (T2DM) incidence. Outcomes were estimated for the general gout population and for gout patients with CKD stages 3/4. Modeled treatment interventions were daily oral febuxostat 40-80 mg and allopurinol 100-300 mg. Baseline patient characteristics were taken from epidemiologic studies, efficacy data from randomized controlled trials, adverse event rates from package inserts, and costs from the literature, government sources, and expert opinion. Eight clinically-relevant incremental cost-effectiveness ratios were estimated: per patient reaching target sUA, per flare avoided, per CKD incidence, progression, stages 3/4 progression, and stage 5 progression avoided, per incident T2DM avoided, and per death avoided. RESULTS Five-year incremental cost-effectiveness ratios for the general gout population were $5377 per patient reaching target sUA, $1773 per flare avoided, $221,795 per incident CKD avoided, $29,063 per CKD progression avoided, $36,018 per progression to CKD 3/4 avoided, $71,426 per progression to CKD 5 avoided, $214,277 per incident T2DM avoided, and $217,971 per death avoided. In patients with CKD 3/4, febuxostat dominated allopurinol for all cost-effectiveness outcome measures. CONCLUSIONS Febuxostat may be a cost-effective alternative to allopurinol, especially for patients with CKD stages 3 or 4.
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Affiliation(s)
- Lee J Smolen
- a a Medical Decision Modeling Inc. , Indianapolis , IN , USA
| | - James C Gahn
- a a Medical Decision Modeling Inc. , Indianapolis , IN , USA
| | | | - Aki Shiozawa
- c c Takeda Pharmaceuticals International, Inc. , Deerfield , IL , USA
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Alani H, Tamimi A, Tamimi N. Cardiovascular co-morbidity in chronic kidney disease: Current knowledge and future research needs. World J Nephrol 2014; 3:156-168. [PMID: 25374809 PMCID: PMC4220348 DOI: 10.5527/wjn.v3.i4.156] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 08/30/2014] [Accepted: 10/16/2014] [Indexed: 02/05/2023] Open
Abstract
Chronic kidney disease (CKD) is recognised as a health concern globally and leads to high rates of morbidity, mortality and healthcare expenditure. CKD is itself an independent risk factor for unfavorable health outcomes that include cardiovascular disease (CVD). Coronary artery disease is the primary type of CVD in CKD patients and a significant cause of death among renal transplant patients. Traditional and non-traditional risk factors for CVD exist in patients with CKD. Traditional factors include smoking, hypertension, dyslipidemia and diabetes which are highly prevalent in CKD patients. Non-traditional risk factors of CKD are mainly uraemia-specific and increase in prevalence as kidney function declines. Some examples of uraemia-specific risk factors that have been well documented include low levels of haemoglobin, albuminuria, and abnormal bone and mineral metabolism. Therapeutic interventions targeted at more traditional risk factors which contribute to CVD, have not had the desired effect on lowering CVD events and mortality in those suffering with CKD. Future research is warranted to delineate clear evidence to the benefit of modifying non-traditional risk factors.
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