MP319DOES ALLOPURINOL IMPROVE CARDIOVASCULAR AND KIDNEY RISK IN NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS?

Abstract

Introduction and Aims: Even recent data on small sample size sustained the beneficial effect of lowering uric acid levels with allopurinol on long-term cardiovascular (CV) risk and chronic kidney disease (CKD) progression, the contribution of hyperuricemia to the decline of glomerular filtration rate (eGFR) and mortality is still an active debate, since converse results were also reported. Consequently, the current retrospective cohort study aims to assess the incidence of CV and renal outcomes in stage 2 to 5 non-dialysis CKD patients constantly treated with allopurinol or not. Methods: Two hundred eighteen non-dialysis CKD subjects with asymptomatic hyperuricemia, from a single centre (56% males, 48% >60 years-old, eGFR 41; 95%CI 38-44mL/min, 26% low, 18% moderate, 34% high and 22% very high risk according to KDIGO classification) were enrolled. Exclusion criteria were: known gout, uric acid lithiasis, kidney graft, nephrotic syndrome, systemic lupus erythematosus, vasculitis and immunosuppressive therapy. Two study groups were defined according to the presence (n=108) or absence (n=110) of allopurinol treatment. Active follow-up method was used (by phone contact and Romanian Renal Registry database search) to assess the incidence of major CV events (death, non-fatal myocardial infarction, stroke, coronary or peripheral revascularization) and of renal replacement therapy (RRT) initiation. Eight subjects in allopurinol-treated group and seventeen in the control group were lost of follow-up. The allopurinol administration and dose (100mg/day) remained unchanged in the studied patients. Results: During the follow-up period of 62 (53;58) months the relative risk (RR) for CV death and non-fatal events in treated subjects was 0.56 [95%CI 0.2-1.47] and 1.27 [95%CI 0.7-2.1], respectively. Less CV deaths occurred in allopurinol-treated group (6% vs. 11%, p=0.001), while a similar incidence of non-fatal CV events was recorded in both groups (12% vs. 13%). Conversely, allopurinol-treated patients had a 27% higher risk of RRT initiation, at least partially explained by the lower eGFR [35 (22;47) vs. 54 (27;58), p=0.003] which probably triggered the more severe KDIGO risk category and was expressed by the higher serum uric acid (6.9±1.7 vs. 5.8±1.6 mg/dL, p=0.001). It worth to emphasize the lower CV mortality in treated group despite its more advanced kidney disease which would be expected to increase the CV risk. However, in a multivariate logistic regression analysis (after adjusting for demographics, comorbidities, eGFR, albumin-to-creatinine ratio (ACR), treatment with statins and anti-angiotensin drugs), allopurinol was not retained as an independent protective factor. The only predictors of poor CV outcome were the absence of statins (OR 5.42; 95%CI 1.6-17.7, p=0.005), higher ACR (OR 2.76; 95%CI 1.4-5.6, p=0.005), and older age. Conclusions: Therefore, even the crude incidence of CV deaths was lower in our allopurinol-treated group, the current results seem not to support an independent effect of hypouricemiant therapy on reducing either CV risk or CKD progression.