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Prevention of kidney function decline using uric acid-lowering therapy in chronic kidney disease patients: a
Shunichiro Tsukamoto1, Naohito Okami1, Takayuki Yamada1,2
1Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Introduction:
Several previous studies have suggested that uric acid-lowering therapy (ULT) can slow the progression of chronic kidney disease (CKD). Although crucial for CKD patients, few studies have evaluated the effects of different ULT medications on kidney function. This systematic review summarizes evidence from randomized controlled trials (RCTs) regarding the effects of ULT on kidney function.
Method:
We performed a systematic search of PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library up to September 2021 to identify RCTs in CKD patients comparing the effects of ULT on kidney function with other ULT medications or placebo. A network meta-analysis was performed to compare each ULT indirectly. The primary outcome was a change in estimated glomerular filtration rate (eGFR) from baseline.
Results:
Ten studies were selected with a total of 1480 patients. Topiroxostat significantly improved eGFR and reduced the urinary albumin/creatinine ratio compared to placebo (mean difference (MD) and 95% confidence interval [95% CI]: 1.49 [0.08; 2.90], P = 0.038 and 25.65% [13.25; 38.04], P < 0.001, respectively). Although febuxostat did not show a positive effect overall, it significantly improved renal function (i.e., eGFR) in a subgroup of CKD patients with hyperuricemia (MD [95% CI]: 0.85 [0.02; 1.67], P = 0.045). Allopurinol and pegloticase did not show beneficial effects.
Conclusions:
Topiroxostat and febuxostat may have better renoprotective effects in CKD patients than other ULT medications. Further large-scale, long-term studies are required to determine whether these effects will lead, ultimately, to reductions in dialysis induction and major adverse cardiovascular events. Key Points • This study is the first network meta-analysis comparing the nephroprotective effects of ULT in CKD patients. • Topiroxostat and febuxostat showed better renoprotective effects in CKD patients than other ULT medications. • Heterogeneity was low in this study, suggesting consistency of results.
Insights
Topiroxostat and febuxostat show potential benefits for kidney function in chronic kidney disease (CKD) patients. This systematic review suggests these uric acid-lowering therapies may offer better renoprotective effects compared to other treatments.
Area of Science:
- Nephrology
- Pharmacology
- Internal Medicine
Background:
- Uric acid-lowering therapy (ULT) is suggested to slow chronic kidney disease (CKD) progression.
- Evaluating the impact of different ULT medications on kidney function in CKD patients is crucial but understudied.
Purpose of the Study:
- To systematically review randomized controlled trials (RCTs) on the effects of ULT on kidney function in CKD patients.
- To compare the efficacy of various ULT medications through network meta-analysis.
Main Methods:
- Systematic literature search of major databases up to September 2021.
- Inclusion of RCTs comparing ULT with placebo or other ULTs in CKD patients.
- Network meta-analysis to indirectly compare ULTs, with estimated glomerular filtration rate (eGFR) as the primary outcome.
Main Results:
- Ten studies with 1480 patients were analyzed.
- Topiroxostat significantly improved eGFR and reduced albuminuria versus placebo.
- Febuxostat showed improved eGFR in a subgroup of CKD patients with hyperuricemia; allopurinol and pegloticase did not demonstrate benefits.
Conclusions:
- Topiroxostat and febuxostat may offer superior renoprotective effects in CKD patients compared to other ULTs.
- Further large-scale, long-term studies are needed to confirm effects on dialysis induction and cardiovascular events.
- Low heterogeneity indicates consistent findings across the included studies.
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