Urate-Lowering Therapy for Preventing Kidney Disease Progression: Are We There Yet?

Tiku, Anushree; Badve, Sunil V.; Johnson, David W.

doi:10.1053/j.ajkd.2018.07.022

Cited by 9 publications

(10 citation statements)

References 18 publications

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“…Although some data suggesting a potential renoprotective effect by allopurinol exists [24][25][26] the available evidence is insufficient to warrant its recommended general use for CKD. 26,27 Furthermore, it is associated with not uncommon severe adverse side-effects, such as allopurinol hypersensitivity syndrome, hepatotoxicity and Stevens-Johnson syndrome. 28,29 Febuxostat, a xanthine oxidase inhibitor also effective at lowering serum uric acid, may have less adverse effects than allopurinol and provide a better benefit-versus-risk profile in its use for renoprotection.…”

Section: Discussionmentioning

confidence: 99%

“…Although some data suggesting a potential renoprotective effect by allopurinol exists 24–26 the available evidence is insufficient to warrant its recommended general use for CKD 26,27 . Furthermore, it is associated with not uncommon severe adverse side‐effects, such as allopurinol hypersensitivity syndrome, hepatotoxicity and Stevens‐Johnson syndrome 28,29 .…”

Section: Discussionmentioning

confidence: 99%

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Febuxostat as a renoprotective agent for treatment of hyperuricaemia: a meta‐analysis of randomised controlled trials

Chewcharat

Chen

Harrison

et al. 2021

Internal Medicine Journal

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Background: The objective of this meta-analysis of randomised controlled clinical trials (RCT) was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia.Aims: Febuxostat is a xanthine oxidase inhibitor that decreases uric acid production.Recent studies suggested the renoprotective effect of febuxostat among hyperuricaemia patients. The aim of this study was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia.Methods: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify RCT that examined the effects of febuxostat in adult patients with hyperuricaemia on serum creatinine, estimated glomerular filtration rate (eGFR), albuminuria, blood pressure parameters, major cardiovascular events, diarrhoea, joint pain, stroke and arrhythmia.Results: Nine RCT with 2141 participants were included in this meta-analysis. Compared to placebo, the febuxostat group showed a higher eGFR at 6 months with a weighted mean difference (WMD) of 2.86 mL/min/1.73 m 2 (P < 0.001), as well as the end of studies (eGFR WMD 2.69 mL/min/1.73 m 2 , P < 0.001). There was also lower serum creatinine (SrCr WMD = −0.04 mg/dL, P < 0.001), reduction in systolic blood pressure (SBP WMD = −1.18 mmHg, P < 0.001) and diastolic blood pressure (DBP WMD = −1.14 mmHg, P = 0.04). There was no statistical difference between febuxostat and placebo in major cardiovascular events, diarrhoea, joint symptoms, stroke events and arrhythmia. Subgroup analysis among chronic kidney disease showed the febuxostat group had higher eGFR than the placebo group (eGFR WMD = 2.69 mL/min/1.73 m 2 , P < 0.001). Conclusion:Treating hyperuricaemia with febuxostat may slow the progression of chronic kidney disease irrespective of baseline renal function without significantly associated increased risks of major cardiovascular events, diarrhoea, joint symptoms, arrhythmia and stroke, compared to placebo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Febuxostat as a renoprotective agent for treatment of hyperuricaemia: a meta‐analysis of randomised controlled trials

Chewcharat

Chen

Harrison

et al. 2021

Internal Medicine Journal

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“…This made it difficult to use the aforementioned primary end points, so the eGFR time × group effect and the mean rate of eGFR decline were used instead. As mentioned earlier, the former is limited by differences in follow-up duration and selection biases, and the latter remains a controversial method of assessing long-term kidney function [23].…”

Section: Discussionmentioning

confidence: 99%

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury

Cho

Park

et al. 2019

JCM

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Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time × group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age-and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time × group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers; however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.

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“…However, whether hyperuricemia is an indirect marker of impaired kidney function or plays a causative role in progression of kidney disease, or both, remains an interesting and unresolved issue for nephrologists ( Sampson et al, 2017 ). The role of uric acid in the development of CKD and whether urate-lowering therapy (ULT) is warranted for its treatment are controversial issues ( Tiku et al, 2018 ; Sato et al, 2019 ; Steiger et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of Drug Treatments for Lowering Uric Acid on Renal Function in Patients With Chronic Kidney Disease and Hyperuricemia: A Network Meta-Analysis of Randomized Controlled Trials

Liu

Qiu

et al. 2021

Front. Pharmacol.

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Background: Hyperuricemia is very common in patients with chronic kidney disease (CKD); the role of hyperuricemia in the occurrence and progression of kidney disease remains an interesting and unresolved issue for nephrologists, and whether urate-lowering therapy (ULT) is warranted in CKD patients is still in controversy. To summarize and compare the clinical outcomes and adverse events (AEs) of three common ULT drugs, we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs).Method: PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched. The network meta-analysis was performed using the “gemtc 0.8-7” and its dependent packages in R software. The primary outcome was the change of renal function and uric acid; creatinine, proteinuria, blood pressure, and adverse events were assessed as the secondary outcomes.Results: 16 RCTs involving 1,943 patients were included in the final network analysis. Febuxostat, allopurinol, and benzbromarone were not found to exert superior effects over placebo upon renoprotective effect. With respect to lowering urate, the three drugs showed to be statistically superior to placebo, while febuxostat could better lower urate than allopurinol (MD: −1.547; 95% CrI: −2.473 to −0.626). It is also indicated that febuxostat was superior to placebo at controlling blood pressure, while no differences were observed when allopurinol and benzbromarone were compared to placebo. These results are stable in subgroup analysis.Conclusion: There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia; febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, but the difference does not reach a statistical significance. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone, and can control blood pressure better.

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Urate-Lowering Therapy for Preventing Kidney Disease Progression: Are We There Yet?

Cited by 9 publications

References 18 publications

Febuxostat as a renoprotective agent for treatment of hyperuricaemia: a meta‐analysis of randomised controlled trials

Febuxostat as a renoprotective agent for treatment of hyperuricaemia: a meta‐analysis of randomised controlled trials

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury

Effectiveness of Drug Treatments for Lowering Uric Acid on Renal Function in Patients With Chronic Kidney Disease and Hyperuricemia: A Network Meta-Analysis of Randomized Controlled Trials

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