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      Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis

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      Publication date (Electronic):
      Journal: PLoS ONE
      Publisher: Public Library of Science

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          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 m 2 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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          Most cited references40

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          Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

          Josef Coresh, Tanvir Turin, Kunihiro Matsushita … (2014)
          The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
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            Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study.

            B Culleton, M Larson, W Kannel … (1999)
            Hyperuricemia is associated with risk for cardiovascular disease and death. However, the role of uric acid independent of established risk factors is uncertain. To examine the relation of serum uric acid level to incident coronary heart disease, death from cardiovascular disease, and death from all causes. Community-based, prospective observational study. Framingham, Massachusetts. 6763 Framingham Heart Study participants (mean age, 47 years). Serum uricacid level at baseline (1971 to 1976); event rates per 1000 person-years by sex-specific uric acid quintile. During 117,376 person-years of follow-up, 617 coronary heart disease events, 429 cardiovascular disease deaths, and 1460 deaths from all causes occurred. In men, after adjustment for age, elevated serum uric acid level was not associated with increased risk for an adverse outcome. In women, after adjustment for age, uric acid level was predictive of coronary heart disease (P = 0.002), death from cardiovascular disease (P = 0.009), and death from all causes (P = 0.03). After additional adjustment for cardiovascular disease risk factors, uric acid level was no longer associated with coronary heart disease, death from cardiovascular disease, or death from all causes. In a stepwise Cox model, diuretic use was identified as the covariate responsible for rendering serum uric acid a statistically nonsignificant predictor of outcomes. These findings indicate that uric acid does not have a causal role in the development of coronary heart disease, death from cardiovascular disease, or death from all causes. Any apparent association with these outcomes is probably due to the association of uric acid level with other risk factors.
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              Maximum Likelihood Approaches to Variance Component Estimation and to Related Problems

              David A. Harville (1977)
              Article 0 comments Cited 262 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Xiaole Su: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Boyang Xu: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Bingjuan Yan: Role: Data curationRole: Formal analysisRole: Software
                Xi Qiao: Role: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Lihua Wang:
                ORCID: http://orcid.org/0000-0001-9908-2816
                Role: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Antonio Carlos Seguro: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 2 November 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 11
                Electronic Location Identifier: e0187550
                Affiliations
                [001]Renal Division, Shanxi Medical University Second Hospital, Taiyuan, Shanxi, China
                Universidade de Sao Paulo Faculdade de Medicina, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-9908-2816
                Article
                Publisher ID: PONE-D-17-27996
                DOI: 10.1371/journal.pone.0187550
                PMC ID: 5667873
                PubMed ID: 29095953
                SO-VID: c2bfd0c6-4d4a-4c7e-8107-fddf14901adf
                Copyright © © 2017 Su et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 26 July 2017
                Date accepted : 20 October 2017
                Page count
                Figures: 4, Tables: 3, Pages: 17
                Funding
                Support was provided by the Science and Technology Project of Shanxi Province (Grant No. 20140313013-5), Natural Science Foundation of Shanxi Province (Grant No. 201701D221173), [ http://www.sxinfo.gov.cn/]; Shanxi Province Health and Family Planning Commission, Science and Technology (Grant No. 201601054), [ http://www.sxwsjs.gov.cn/]. The funders had no role in decision to publish and preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Nephrology
                Subject: Chronic Kidney Disease
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Renal System
                Subject: Kidneys
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Renal System
                Subject: Kidneys
                Subject: Medicine and Health Sciences
                Subject: Pharmaceutics
                Subject: Drug Therapy
                Subject: Cardiovascular Therapy
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Renal Physiology
                Subject: Glomerular Filtration Rate
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Renal Physiology
                Subject: Glomerular Filtration Rate
                Subject: Biology and Life Sciences
                Subject: Population Biology
                Subject: Population Metrics
                Subject: Death Rates
                Subject: Physical Sciences
                Subject: Chemistry
                Subject: Chemical Compounds
                Subject: Acids
                Subject: Uric Acid
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Biomarkers
                Subject: Creatinine
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Signs and Symptoms
                Subject: Proteinuria
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Signs and Symptoms
                Subject: Proteinuria
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

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                ScienceOpen disciplines: Uncategorized

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