Febuxostat for Asymptomatic Hyperuricemia in CKD.

Abstract

We are greatly interested in the article by Sircar et al,1Sircar D. Chatterjee S. Waikhom R. et al.Efficacy of febuxostat for slowing the GFR decline in patients with CKD and asymptomatic hyperuricemia: a 6-month double-blind, randomized, placebo-controlled trial.Am J Kidney Dis. 2015; 66: 945-950Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar which demonstrates the efficacy of febuxostat in retarding estimated glomerular filtration rate decline in patients with chronic kidney disease (CKD) and asymptomatic hyperuricemia. Numerous studies have demonstrated a relationship between serum uric acid levels and cardiovascular morbid entities, including kidney diseases.2Zhao G. Huang L. Song M. Song Y. Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: a meta-analysis of prospective studies.Atherosclerosis. 2013; 231: 61-68Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar Others have explored the effectiveness of conventional hypouricemic agents such as allopurinol in slowing CKD progression.3Zhang Y.F. He F. Ding H.H. et al.Effect of uric acid lowering agent on progression of chronic kidney disease: a meta-analysis.J Huazhong Univ Sci Technol Med Sci. 2014; 34: 476-481Crossref PubMed Scopus (16) Google Scholar This study appears to demonstrate the cause-effect relationship between hyperuricemia and CKD and the clinical effectiveness of febuxostat, a nonpurine selective xanthine oxidase inhibitor. Results from this study could potentially affect current CKD management guidelines, particularly in the Western world, where pharmacotherapy for asymptomatic hyperuricemia is not proactively recommended. We recognize the study limitations, including small size and short follow-up, and are concerned about the generalizability of the results. In addition, the authors do not comment about whether a statistically significant difference exists in baseline characteristics between the groups, notably age, sex, proteinuria, body mass index, dietary factors, and alcohol use. We wonder how much confounding effect these parameters have on the results, considering that they are established independent risk factors for a decline in kidney function.4Fox C.S. Larson M.G. Leip E.P. Culleton B. Wilson P.W. Levy D. Predictors of new-onset kidney disease in a community-based population.JAMA. 2004; 291: 844-850Crossref PubMed Scopus (983) Google Scholar, 5Lu J.L. Molnar M.Z. Naseer A. Mikkelsen M.K. Kilantar-Zadeh K. Kovesdy C.P. Association of age and BMI with kidney function and mortality: a cohort study.Lancet Diabetes Endocrinol. 2015; 3: 704-714Abstract Full Text Full Text PDF Scopus (139) Google Scholar We agree that more studies with larger population size are needed to fully explore not only the clinical benefits of febuxostat, but also adverse effects, such as rhabdomyolysis6Ghosh D. McGann P.M. Furlong T.J. Day R.O. Febuxostat associated rhabdomyolysis in chronic renal failure.Med J Aust. 2015; 203: 107-108Crossref PubMed Scopus (12) Google Scholar and elevated liver function test results. We suggest that future trials specifically address the possible confounders mentioned. Furthermore, we propose including serum cystatin C, a more sensitive marker for kidney function,7Wei L. Ye X. Pei X. Wu J. Zhao W. Diagnostic accuracy of serum cystatin C in chronic kidney disease: a meta-analysis.Clin Nephrol. 2015; 84: 86-94Crossref PubMed Scopus (15) Google Scholar, 8Oh S.J. Lee J.I. Ha W.C. et al.Comparison of cystatine C and creatinine based estimation of glomerular filtration rate according to glycaemic status in type 2 diabetes.Diabet Med. 2012; 29: 121-125Crossref PubMed Scopus (11) Google Scholar to better appreciate the effects of febuxostat. Financial Disclosure: The authors declare that they have no relevant financial interests. Peer Review: Evaluated by a Co-Editor and the Editor-in-Chief. Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia: A 6-Month, Double-Blind, Randomized, Placebo-Controlled TrialAmerican Journal of Kidney DiseasesVol. 66Issue 6PreviewHyperuricemia is a putative risk factor for the progression of chronic kidney disease (CKD). We hypothesized that control of asymptomatic hyperuricemia may slow disease progression in CKD. Full-Text PDF In Reply to ‘Febuxostat for Asymptomatic Hyperuricemia in CKD' and ‘Febuxostat Renoprotection in CKD Patients With Asymptomatic Hyperuricemia’American Journal of Kidney DiseasesVol. 67Issue 6PreviewWe agree with Mome and Bakinde1 that our study has a lack of generalizability because the population was solely from Eastern India. However, of note, Goicoechea et al2 have demonstrated the effects of allopurinol in a Spanish cohort. Significance tests of baseline differences have been discouraged by the CONSORT statement,3 and it has been suggested that such testing does not provide an appropriate criterion to assess the effect of imbalance on outcome or the decision to adjust for baseline variables. Full-Text PDF