Reducing serum uric acid levels using a treat-to-target approach with xanthine oxidase inhibitors may improve renal function in patients with gout and stage 3 chronic kidney disease (CKD), according to study results published in Rheumatology International.1

Studies have showed that hyperuricemia and gout are associated with several comorbidities, including renal disease. Urate-lowering therapy with xanthine oxidase inhibitors has been shown to improve renal function in patients with CKD; however, current guideline-recommended dosage restrictions2 make it difficult for clinicians to treat this patient population with urate-lowering therapy.

The objective of this study was to evaluate the efficacy and safety of xanthine oxidase inhibitors using a treat-to-target approach in patients with gout and stage 3 CKD.

In this multicenter observational retrospective study, researchers reviewed clinical records of patients with gout and stage 3 CKD who received xanthine oxidase inhibitors (allopurinol or febuxostat) using a treat-to-target approach for at least 12 months. Data were assessed at baseline and at 6 and 12 months. Demographic and clinical features examined included age, sex, serum uric acid levels, comorbidities, smoking habits, and alcohol use. A linear mixed-effects model was used to analyze the effects of independent variables over estimated glomerular filtration rate (eGFR).


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The study included complete data from 50 patients (mean age, 72.90±8.94 years; 44 men) who met the inclusion criteria, and among whom 82% achieved the therapeutic serum uric acid target during the 12-month study period. The improvement in eGFR was higher during the first 6 months and showed a median increase of 7.54 mL/min/m2 (standard error [SE], 1.25), which trended towards stability during the 12 months.

Bivariate analysis from mixed effect regression showed that eGFR was significantly correlated with time, serum uric acid levels, sex, and treatment (β-coefficient±SE, -7.54±1.25 mL/min/m2 , -1.57±0.26 mL/min/m2 , -11.17±3.70 mL/min/m2 , and -7.21±2.45 mL/min/m2 , respectively). There were no significant differences in eGFR changes between febuxostat and allopurinol; no adverse events with urate-lowering therapy were reported. Multivariate analysis, which included all the factors from the bivariate analysis and smoking habit, showed that eGFR changed in accordance with serum uric acid levels (β-coefficient±SE=-1.58±0.26 mL/min/m2; P <.001), at a rate of 1.5 mL/min/m2 for every 1 mg/dL of decrease in serum uric acid levels. Higher eGFR values were seen with colchicine administration and among men vs women, while lower eGFR values were observed with age and among current smokers vs nonsmokers.

Study limitations included retrospective design, small sample size, lack of a control group and data on doses of concomitant treatments, and possible confounders, including the natriuretic effect of other drugs used.

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“[I]ntensive reductions in [serum uric acid] levels trended towards achieving a successful treat-to-target approach in gouty patients with moderate CKD. This approach helped to conserve and improve renal function in patients [with] CKD stage 3 treated with [xanthine oxidase inhibitors] (either allopurinol or febuxostat) at optimal doses without serious drug-related adverse events in clinical practice, suggesting that there is a window of opportunity for this set of patients,” the researchers concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

1. Novella-Navarro M, Cabrera-Alarcon JL, Diaz-Torne C, et al. A treat-to-target approach for gout confers renoprotective effect in patients with chronic kidney disease stage 3 [published online January 25, 2020]. Rheumatol Int. doi:10.1007/s00296-020-04517-4

2. Richette P, Doherty M, Pascual E, Barskova V, Becce F,Castañeda-Sanabria J et al. 2016 Updated EULAR evidence based-recommendations for the management of gout. Ann Rheum Dis. 2017;76:29-42.