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

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BARTÁKOVÁ Vendula KURICOVÁ Katarína PÁCAL Lukáš NOVÁ Zuzana DVOŘÁKOVÁ Veronika ŠVRČKOVÁ Martina MALÚŠKOVÁ Denisa SVOBODOVÁ Ivana ŘEHOŘOVÁ Jitka SVOJANOVSKÝ Jan OLŠOVSKÝ Jindřich BĚLOBRÁDKOVÁ Jana KAŇKOVÁ Kateřina

Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Diabetes and its Complications
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://www.sciencedirect.com/science/article/pii/S1056872716301829
Doi http://dx.doi.org/10.1016/j.jdiacomp.2016.06.002
Obor Endokrinologie, diabetologie, metabolismus, výživa
Klíčová slova Diabetic kidney disease; uric acid; allopurinol; type 2 diabetes mellitus; mortality; single nucleotide polymorphism
Popis The aims of the study: (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. Study comprised 422 subjects with diabetes duration at least 15 years. 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 above 420 umol/l for men and above 360 umol/l for women and/or allopurinol treatment). Five SNPs in the SLC2A9 and ABCG2 genes were determined by PCR. Time-to-event analysis with subgroups defined by the presence/absence of initial hyperuricemia revealed significant differences in all three end-points (P les than 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 less than 377.5 umol/l for men and less than 309.0 umol/l for women. We found no differences in allele or genotype frequencies in selected SNPs between patients with and without hyperuricemia (all P more than 0.05). Initial hyperuricemia or need for allopurinol are independent risk factors for DKD progression and that SUA levels in diabetics subjects conferring protection against DKD progression might be lower than current cut-offs for general population.
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