Changes in fat mass after initiation of maintenance dialysis is influenced by the uncoupling protein 2 exon 8 insertion/deletion polymorphism

Abstract

A high body mass index (BMI) has been reported to confer a survival advantage in end-stage renal disease (ESRD) patients. On the other hand, body fat accumulation, especially visceral adipose tissue, is an important risk factor for cardiovascular disease, as well as a clinically important source of adipokines. Uncoupling protein 2 (UCP2) uncouples respiration from ATP synthesis, thus regulating energy expenditure and fat oxidation. In this longitudinal cohort study, we investigated the impact of the UCP2 insertion/deletion (ins/del) polymorphism on body composition changes in ESRD patients starting dialysis. A total of 222 incident Caucasian ESRD patients (mean age 53 +/- 12 years; 60% males) were investigated close to the start of dialysis with peritoneal dialysis (PD; n = 126) or haemodialysis (HD; n = 96), and again after about 1 year (n = 159). Genotyping of the UCP2 ins/del polymorphism was performed in the patients and in 207 healthy controls. Dual-energy X-ray absorptiometry was conducted at baseline and after 1 year to monitor body composition. While HD patients and PD patients with the ins/del genotype did not display any changes in body composition, the 48 PD patients with the del/del genotype that completed follow-up had a significant increase; DeltaBMI (0.7 +/- 1.8 kg/m(2)), Deltabody fat mass (3.5 +/- 3.8 kg) and Deltatruncal fat mass (1.7 +/- 1.2 kg). In a multiple linear regression analysis, the del/del genotype was an independent predictor of the increase in truncal fat mass in PD patients (F-ratio = 7.99, P < 0.05) together with age and diabetes mellitus. PD patients, but not HD patients, with the UCP2 del/del genotype showed a significant increase in total and truncal fat mass during the first year of dialysis therapy, suggesting a possible role for UCP2 in dissipating the excess energy of a high-glucose environment.