Hyperuricemia contributes to the faster progression of diabetic kidney disease in type 2 diabetes mellitus

Aims: The aims of the study were (i) to ascertain prognostic value of serum uric acid (SUA) for diabetic kidney disease (DKD) progression and major adverse cardiovascular event (MACE) in a cohort of T2DM patients, (ii) to ascertain eventual protective effect of allopurinol treatment, (iii) to determine the effect of genetic variability in UA transporters on DKD progression, and (iv) to define optimal cut-off values for SUA in patients with DKD. Methods: Study comprised 422 subjects with diabetes duration at least 15 years followed-up for a median of 43 [IQR 22-77] months. Participants were categorized into stable or progressors according to their change in albuminuria or chronic kidney disease (CKD) stage. At baseline, 68% patients had hyperuricemia (SUA >= 420 mu mol/l for men and >= 360 mu mol/l for women and/or allopurinol treatment). Five SNPs in the SLC2A9 and ABCG2 genes were determined by PCR. Results: Time-to-event analysis with subgroups defined by the presence/absence of initial hyperuricemia revealed significant differences in all three end-points (P < 0.0001 for DKD progression, P = 0.0022 for MACE and P = 0.0002 for death, log-rank test). Subjects with normal SUA not requiring allopurinol had median time to DKD progression 49 months compared with remaining subjects (32 months, P = 0.0002, log-rank test). Multivariate Cox regression model revealed hyperuricemia (i.e. high SUA and/or allopurinol treatment) significant predictor of DKD progression independent of baseline CKD stage. Optimal cut-off values identified by ROC analysis for T2DM subjects were <= 377.5 mu mol/l for men and <= 309.0 mu mol/l for women. We found no differences in allele or genotype frequencies in selected SNPs between patients with and without hyperuricemia (all P > 0.05). Conclusions: Our study demonstrated that initial hyperuricemia or need for allopurinol is an independent risk factor for DKD progression and that SUA levels in diabetic subjects conferring protection against DKD progression might be lower than current cut-offs for general population. (C) 2016 Elsevier Inc. All rights reserved.