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Hyperuricaemia contributes to the faster progression of diabetic kidney disease and all-cause mortality in type 2 diabetes



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Popis Objective Multiple studies have shown that elevated serum uric acid (SUA) levels are associated with higher risk of renal events among the people with type 1 diabetes but only few studies addressed the role of SUA on progression of diabetic kidney disease (DKD) in type 2 diabetic (T2DM) patients. Many studies now focused on glucose transporter member 9 (GLUT9), as glucose transporter as a high-capacity uric acid transporter, encoded by the SLC2A9 gene. Gene ATP binding cassette, subfamily G, member 2 (ABCG2), is hypothesized to excrete uric acid. The objective of this study was to investigate the contribution of baseline SUA levels and genetic variability in selected genes involved in urate homeostasis on DKD. Method The prospective cohort study comprised 422 T2DM Caucasian subjects, South Moravia region of Czech Republic, with variable stage of DN at baseline, followed for a median 47 [IQR 27 - 79] months. Subjects were considered to have hyperuricaemia when their initial SUA levels were ?420 umol/l for men and ?360umol/l for women, or if they were treated by allopurinol at the time of enrolment in the study. Following end-points were considered: (1) progression of DKD (based on the level of proteinuria and GFR) and (2) major adverse cardiovascular event (MACE) non-cardiovascular mortality was considered a competing risk. Genotyping of 5 SNPs (4 in the SLC2A9 gene and 1 in the ABCG2 gene) was performed by RT-PCR. Time-to-event and competing risk analysis was carried out to ascertain contribution of parameters to studied end-points. Results Cumulative incidence of DKD progression was 54.4 %, MACE 32.2 % and all-cause mortality 43.8 %. Baseline hyperuricaemia proved to be significant risk factor of DKD progression and MACE events (P < 0.00001 and P = 0.0021) with allopurinol treatment exhibiting a protective effect independent on SUA level. We found no significant differences in carriage of risk genotype between subgroups in any of selected SNPs. Conclusions Our results indicate that hyperuricaemia contributes to the progression of diabetes-associated morbidity or mortality. Acknowledgment: Study was supported by the grant NT11405, Ministry of Health of Czech Republic.
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