Haptoglobin genotype and the rate of renal function decline in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study

Trevor J Orchard, Wanjie Sun, Patricia A Cleary, Saul M Genuth, John M Lachin, Paula McGee, Andrew D Paterson, Philip Raskin, Yefim Anbinder, Andrew P Levy, DCCT/EDIC Research Group, Trevor J Orchard, Wanjie Sun, Patricia A Cleary, Saul M Genuth, John M Lachin, Paula McGee, Andrew D Paterson, Philip Raskin, Yefim Anbinder, Andrew P Levy, DCCT/EDIC Research Group

Abstract

Many patients with type 1 diabetes develop renal disease despite moderately good metabolic control, suggesting other risk factors may play a role. Recent evidence suggests that the haptoglobin (HP) 2-2 genotype, which codes for a protein with reduced antioxidant activity, may predict renal function decline in type 1 diabetes. We examined this hypothesis in 1,303 Caucasian participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. HP genotype was determined by polyacrylamide gel electrophoresis. Glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and albumin excretion based on timed urine samples. Participants were followed up for a mean of 22 years. HP genotype was significantly associated with the development of sustained estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) and with end-stage renal disease (ESRD), with HP 2-2 having greater risk than HP 2-1 and 1-1. No association was seen with albuminuria. Although there was no treatment group interaction, the associations were only significant in the conventional treatment group, where events rates were much higher. We conclude that the HP genotype is significantly associated with the development of reduced GFR and ESRD in the DCCT/EDIC study.

Trial registration: ClinicalTrials.gov NCT00360815 NCT00360893.

Figures

FIG. 1.
FIG. 1.
Cumulative incidence of sustained GFR 2 in the 1,303 Caucasian DCCT/EDIC participants by HP type 1-1, 2-1, and 2-2. P value is from a log-rank trend test.
FIG. 2.
FIG. 2.
Cumulative incidence of ESRD in the 1,303 Caucasian DCCT/EDIC participants by HP type 1-1, 2-1, and 2-2. P value is from a log-rank trend test.

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