Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis

Abstract

Background: Accruing evidence suggests that Xanthine Oxidase inhibitors (XOis) may bring direct renal benefits, besides those related to their hypo-uricemic effect. We hence aimed at performing a systematic review of randomized controlled trials (RCTs) to verify if treatment with XOis may improve renal outcomes in individuals with chronic kidney disease (CKD). Methods: Ovid-MEDLINE, PubMed and CENTRAL databases were searched for RCTs comparing any XOi to standard therapy or placebo. The primary endpoint of interest was progression to End-Stage Kidney Disease (ESKD); secondary endpoints were changes in serum creatinine, glomerular filtration rate (eGFR), proteinuria and albuminuria. Results: XOis treatment significantly reduced the risk of ESKD compared to the control (3 studies, 204 pts; RR = 0.42; 95% CI, 0.22, 0.80) and also improved eGFR in data pooled from RCTs with long follow-up times (>3 mo.) (4 studies, 357 pts; mean difference (MD) 6.82 mL/min/1.73 m2; 95% CI, 3.50, 10.15) and high methodological quality (blind design) (3 studies, 400 pts; MD 2.61 mL/min/1.73 m2; 95% CI, 0.23, 4.99). Conversely, no definite effects were apparently noticed on serum creatinine, proteinuria and albuminuria. Conclusions: XOis may represent a promising tool for retarding disease progression in CKD patients. Future trials are awaited to confirm the generalizability of these findings to the whole CKD population.

Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial

“…1 Furthermore, information for the effects of xanthine oxidase inhibitors on early kidney damage is sparse or lacking. 9 Febuxostat, a novel potent nonpurine-selective inhibitor of xanthine oxidase for oral use, is metabolized predominantly in the liver by glucuronidation, with only 1% to 6% of the dose being excreted unchanged through the kidneys. 10 Hence, decreased glomerular filtration rate (GFR) has little impact on the pharmacokinetic profile of febuxostat, 11 allowing its safe administration for patients with low GFRs.…”

Risks of female genital tract related cancers (gynecological cancers) or breast cancer in women with and without chronic kidney disease

“…This is an unexpected finding, as many studies suggested that cancer risk would be increased in the CKD patients. [ 7 – 12 , 21 – 31 ] The further surprising finding was that our study showed a negative association between CKD and GC.…”

Fructose and Uric Acid: Major Mediators of Cardiovascular Disease Risk Starting at Pediatric Age

“…This hypothesis might explain the conflicting results reported in studies investigating the use of urate- lowering treatments in adults with established hypertension or chronic renal disease. Thus, at variance with these data, small pilot studies conducted in children and adolescents showed a reduction in blood pressure [ 63 , 64 ] and improvement in insulin sensitivity [ 99 , 100 ] and CKD [ 101 ] with the use of urate-lowering treatments. We believe further studies are needed before definitive conclusions can be drawn regarding the reversibility of the mechanisms sustaining the relationship between fructose, uric acid and all the metabolic dysregulations.…”