Effects of uric acid-lowering therapy on renal outcomes

A systematic review and meta-analysis

Bhadran Bose, Sunil Badve, Swapnil Hiremath, Neil Boudville, Fiona Brown, Alan Cass, Janak de Zoysa, Robert Fassett, Randall Faull, David Harris, Carmel Hawley, John Kanellis, Suetonia Palmer, Vlado Perkovic, Elaine Pascoe, Gopala Rangan, Robert Walker, Giles Walters, David Johnson

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes.

    Methods: Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis.

    Results: Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) −0.9, 7.1; heterogeneity χ2 = 1.9, I2 = 0%, P = 0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD −0.4 mg/dL, 95% CI −0.8, −0.0 mg/dL; heterogeneity χ2 = 3, I2 = 34%, P = 0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events.

    Conclusions: Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.
    Original languageEnglish
    Pages (from-to)406-413
    Number of pages8
    JournalNephrology Dialysis Transplantation
    Volume29
    Issue number2
    DOIs
    Publication statusPublished - 2014

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    Uric Acid
    Allopurinol
    Meta-Analysis
    Kidney
    Chronic Renal Insufficiency
    Therapeutics
    Randomized Controlled Trials
    Confidence Intervals
    Serum
    Glomerular Filtration Rate
    Proteinuria
    Chronic Kidney Failure
    Creatinine
    Language
    Placebos
    Databases
    Blood Pressure

    Cite this

    Bose, Bhadran ; Badve, Sunil ; Hiremath, Swapnil ; Boudville, Neil ; Brown, Fiona ; Cass, Alan ; de Zoysa, Janak ; Fassett, Robert ; Faull, Randall ; Harris, David ; Hawley, Carmel ; Kanellis, John ; Palmer, Suetonia ; Perkovic, Vlado ; Pascoe, Elaine ; Rangan, Gopala ; Walker, Robert ; Walters, Giles ; Johnson, David. / Effects of uric acid-lowering therapy on renal outcomes : A systematic review and meta-analysis. In: Nephrology Dialysis Transplantation. 2014 ; Vol. 29, No. 2. pp. 406-413.
    @article{bb74b29f26604765a2901c925f61f867,
    title = "Effects of uric acid-lowering therapy on renal outcomes: A systematic review and meta-analysis",
    abstract = "Background: Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes.Methods: Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis.Results: Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95{\%} confidence intervals (CI) −0.9, 7.1; heterogeneity χ2 = 1.9, I2 = 0{\%}, P = 0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD −0.4 mg/dL, 95{\%} CI −0.8, −0.0 mg/dL; heterogeneity χ2 = 3, I2 = 34{\%}, P = 0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events.Conclusions: Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.",
    keywords = "allopurinol, creatinine, placebo, uric acid, aplastic anemia, blood pressure, chronic kidney disease, controlled study, creatinine blood level, death, drug efficacy, drug safety, end stage renal disease, glomerulus filtration rate, human, kidney function, major clinical study, meta analysis, priority journal, proteinuria, randomized controlled trial, rash, review, risk benefit analysis, Stevens Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis, uric acid blood level, clinical trial, kidney function test, renal dialysis, Allopurinol, Disease Progression, Gout Suppressants, Humans, Renal Insufficiency, Chronic, Uric Acid",
    author = "Bhadran Bose and Sunil Badve and Swapnil Hiremath and Neil Boudville and Fiona Brown and Alan Cass and {de Zoysa}, Janak and Robert Fassett and Randall Faull and David Harris and Carmel Hawley and John Kanellis and Suetonia Palmer and Vlado Perkovic and Elaine Pascoe and Gopala Rangan and Robert Walker and Giles Walters and David Johnson",
    year = "2014",
    doi = "10.1093/ndt/gft378",
    language = "English",
    volume = "29",
    pages = "406--413",
    journal = "Nephrology Dialysis Transplantation",
    issn = "0931-0509",
    publisher = "Oxford University Press",
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    }

    Bose, B, Badve, S, Hiremath, S, Boudville, N, Brown, F, Cass, A, de Zoysa, J, Fassett, R, Faull, R, Harris, D, Hawley, C, Kanellis, J, Palmer, S, Perkovic, V, Pascoe, E, Rangan, G, Walker, R, Walters, G & Johnson, D 2014, 'Effects of uric acid-lowering therapy on renal outcomes: A systematic review and meta-analysis', Nephrology Dialysis Transplantation, vol. 29, no. 2, pp. 406-413. https://doi.org/10.1093/ndt/gft378

    Effects of uric acid-lowering therapy on renal outcomes : A systematic review and meta-analysis. / Bose, Bhadran; Badve, Sunil; Hiremath, Swapnil; Boudville, Neil; Brown, Fiona; Cass, Alan; de Zoysa, Janak; Fassett, Robert; Faull, Randall; Harris, David; Hawley, Carmel; Kanellis, John; Palmer, Suetonia; Perkovic, Vlado; Pascoe, Elaine; Rangan, Gopala; Walker, Robert; Walters, Giles; Johnson, David.

    In: Nephrology Dialysis Transplantation, Vol. 29, No. 2, 2014, p. 406-413.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Effects of uric acid-lowering therapy on renal outcomes

    T2 - A systematic review and meta-analysis

    AU - Bose, Bhadran

    AU - Badve, Sunil

    AU - Hiremath, Swapnil

    AU - Boudville, Neil

    AU - Brown, Fiona

    AU - Cass, Alan

    AU - de Zoysa, Janak

    AU - Fassett, Robert

    AU - Faull, Randall

    AU - Harris, David

    AU - Hawley, Carmel

    AU - Kanellis, John

    AU - Palmer, Suetonia

    AU - Perkovic, Vlado

    AU - Pascoe, Elaine

    AU - Rangan, Gopala

    AU - Walker, Robert

    AU - Walters, Giles

    AU - Johnson, David

    PY - 2014

    Y1 - 2014

    N2 - Background: Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes.Methods: Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis.Results: Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) −0.9, 7.1; heterogeneity χ2 = 1.9, I2 = 0%, P = 0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD −0.4 mg/dL, 95% CI −0.8, −0.0 mg/dL; heterogeneity χ2 = 3, I2 = 34%, P = 0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events.Conclusions: Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.

    AB - Background: Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes.Methods: Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis.Results: Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) −0.9, 7.1; heterogeneity χ2 = 1.9, I2 = 0%, P = 0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD −0.4 mg/dL, 95% CI −0.8, −0.0 mg/dL; heterogeneity χ2 = 3, I2 = 34%, P = 0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events.Conclusions: Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.

    KW - allopurinol

    KW - creatinine

    KW - placebo

    KW - uric acid

    KW - aplastic anemia

    KW - blood pressure

    KW - chronic kidney disease

    KW - controlled study

    KW - creatinine blood level

    KW - death

    KW - drug efficacy

    KW - drug safety

    KW - end stage renal disease

    KW - glomerulus filtration rate

    KW - human

    KW - kidney function

    KW - major clinical study

    KW - meta analysis

    KW - priority journal

    KW - proteinuria

    KW - randomized controlled trial

    KW - rash

    KW - review

    KW - risk benefit analysis

    KW - Stevens Johnson syndrome

    KW - thrombocytopenia

    KW - toxic epidermal necrolysis

    KW - uric acid blood level

    KW - clinical trial

    KW - kidney function test

    KW - renal dialysis

    KW - Allopurinol

    KW - Disease Progression

    KW - Gout Suppressants

    KW - Humans

    KW - Renal Insufficiency, Chronic

    KW - Uric Acid

    U2 - 10.1093/ndt/gft378

    DO - 10.1093/ndt/gft378

    M3 - Article

    VL - 29

    SP - 406

    EP - 413

    JO - Nephrology Dialysis Transplantation

    JF - Nephrology Dialysis Transplantation

    SN - 0931-0509

    IS - 2

    ER -