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

Abstract

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 15years 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≥420μmol/l for men and ≥360μmol/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 49months compared with remaining subjects (32months, 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 ≤377.5μmol/l for men and ≤309.0μmol/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.

• Authors: Vendula Bartáková, Katarína Kuricová, Lukáš Pácal, Zuzana Nová, Veronika Dvořáková, Martina Švrčková, Denisa Malúšková, Ivana Svobodová, Jitka Řehořová, Jan Svojanovský, Jindřich Olšovský, Jana Bělobrádková, Kateřina Kaňková
• Journal: Journal of diabetes and its complications (J Diabetes Complications) 2016 Sep-Oct Vol. 30 Issue 7 Pg. 1300-7 ISSN: 1873-460X [Electronic] United States
• PMID: 27324705 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• Glucose Transport Proteins, Facilitative
• Neoplasm Proteins
• SLC2A9 protein, human
• Uric Acid
• Allopurinol

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2 (genetics)
• Aged
• Albuminuria (physiopathology)
• Allopurinol (therapeutic use)
• Diabetes Mellitus, Type 2 (complications)
• Diabetic Nephropathies (physiopathology)
• Disease Progression
• Female
• Glucose Transport Proteins, Facilitative (genetics)
• Humans
• Hyperuricemia (drug therapy, physiopathology)
• Male
• Neoplasm Proteins (genetics)
• Polymorphism, Single Nucleotide
• Proportional Hazards Models
• Renal Insufficiency, Chronic (physiopathology)
• Risk Factors
• Uric Acid (blood)