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



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.



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).



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.
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. Electronic address: vbartak@med.muni.cz.
Vendula
V
Bartáková
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Katarína
K
Kuricová
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Lukáš
L
Pácal
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Zuzana
Z
Nová
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Veronika
V
Dvořáková
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Martina
M
Švrčková
Institute of Biostatistics and Analyses, Masaryk University, Netroufalky 797/5, 625 00 Brno, Czech Republic.
Denisa
D
Malúšková
Institute of Biostatistics and Analyses, Masaryk University, Netroufalky 797/5, 625 00 Brno, Czech Republic.
Ivana
I
Svobodová
Diabetes Centre, Department of Internal Medicine - Gastroenterology, University Hospital Brno, Jihlavská 20, 625 00 Brno, Czech Republic.
Jitka
J
Řehořová
Nephrology & Dialysis Unit, The 2nd Department of Internal Medicine, St. Anne's University Hospital, Pekařská 53, 656 91 Brno, Czech Republic.
Jan
J
Svojanovský
Nephrology & Dialysis Unit, The 2nd Department of Internal Medicine, St. Anne's University Hospital, Pekařská 53, 656 91 Brno, Czech Republic.
Jindřich
J
Olšovský
Diabetes Centre, Department of Internal Medicine - Gastroenterology, University Hospital Brno, Jihlavská 20, 625 00 Brno, Czech Republic.
Jana
J
Bělobrádková
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Kateřina
K
Kaňková
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics; D000368:Aged; D000419:Albuminuria / Q000503:physiopathology; D000493:Allopurinol / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D051246:Glucose Transport Proteins, Facilitative; D009363:Neoplasm Proteins; C411811:SLC2A9 protein, human; D014527:Uric Acid; D000493:Allopurinol
Allopurinol; Diabetic kidney disease; Mortality; Single nucleotide polymorphism; Type 2 diabetes mellitus; Uric acid