Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis

Bhadran Bose; Sunil V Badve; Swapnil S Hiremath; Neil Boudville; Fiona G Brown; Alan Cass; Janak R de Zoysa; Robert G Fassett; Randall J Faull; David C H Hamlyn Harris; Carmel Mary Hawley; John Kanellis; Suetonia C Palmer; Vlado Perkovic; Elaine Pascoe; Gopala K Rangan; Robert James Walker; Giles D Walters; David W Johnson

doi:10.1093/ndt/gft378

Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis

Bhadran Bose, Sunil V Badve, Swapnil S Hiremath, Neil Boudville, Fiona G Brown, Alan Cass, Janak R de Zoysa, Robert G Fassett, Randall J Faull, David C H Hamlyn Harris, Carmel Mary Hawley, John Kanellis, Suetonia C Palmer, Vlado Perkovic, Elaine Pascoe, Gopala K Rangan, Robert James Walker, Giles D Walters, David W Johnson

Medicine Monash Health

Research output: Contribution to journal › Article › Research › peer-review

183 Citations (Scopus)

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 chi2=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 chi2=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 language	English
Pages (from-to)	406 - 413
Number of pages	8
Journal	Nephrology Dialysis Transplantation
Volume	29
Issue number	2
DOIs	https://doi.org/10.1093/ndt/gft378
Publication status	Published - 2014

Access to Document

10.1093/ndt/gft378

Cite this

Bose, B., Badve, S. V., Hiremath, S. S., Boudville, N., Brown, F. G., Cass, A., de Zoysa, J. R., Fassett, R. G., Faull, R. J., Harris, D. C. H. H., Hawley, C. M., Kanellis, J., Palmer, S. C., Perkovic, V., Pascoe, E., Rangan, G. K., Walker, R. J., Walters, G. D., & Johnson, D. W. (2014). Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis. Nephrology Dialysis Transplantation, 29(2), 406 - 413. https://doi.org/10.1093/ndt/gft378

@article{ec8652d8bb5d44b29dc86f6a4a21bb01,

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 chi2=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 chi2=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.",

author = "Bhadran Bose and Badve, {Sunil V} and Hiremath, {Swapnil S} and Neil Boudville and Brown, {Fiona G} and Alan Cass and {de Zoysa}, {Janak R} and Fassett, {Robert G} and Faull, {Randall J} and Harris, {David C H Hamlyn} and Hawley, {Carmel Mary} and John Kanellis and Palmer, {Suetonia C} and Vlado Perkovic and Elaine Pascoe and Rangan, {Gopala K} and Walker, {Robert James} and Walters, {Giles D} and Johnson, {David W}",

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",

number = "2",

}

Bose, B, Badve, SV, Hiremath, SS, Boudville, N, Brown, FG, Cass, A, de Zoysa, JR, Fassett, RG, Faull, RJ, Harris, DCHH, Hawley, CM, Kanellis, J, Palmer, SC, Perkovic, V, Pascoe, E, Rangan, GK, Walker, RJ, Walters, GD & Johnson, DW 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

TY - JOUR

T1 - Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis

AU - Bose, Bhadran

AU - Badve, Sunil V

AU - Hiremath, Swapnil S

AU - Boudville, Neil

AU - Brown, Fiona G

AU - Cass, Alan

AU - de Zoysa, Janak R

AU - Fassett, Robert G

AU - Faull, Randall J

AU - Harris, David C H Hamlyn

AU - Hawley, Carmel Mary

AU - Kanellis, John

AU - Palmer, Suetonia C

AU - Perkovic, Vlado

AU - Pascoe, Elaine

AU - Rangan, Gopala K

AU - Walker, Robert James

AU - Walters, Giles D

AU - Johnson, David W

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 chi2=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 chi2=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 chi2=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 chi2=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.

UR - http://ndt.oxfordjournals.org/content/29/2/406.full.pdf

U2 - 10.1093/ndt/gft378

DO - 10.1093/ndt/gft378

M3 - Article

SN - 0931-0509

VL - 29

SP - 406

EP - 413

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

IS - 2

ER -

Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis

Abstract

Access to Document

Other files and links

Cite this