Fat tissue accumulation during peritoneal dialysis is associated with a polymorphism in uncoupling protein 2

Chronic treatment with peritoneal dialysis (PD) is a unique long-term metabolic procedure entailing a continuous 24-hour supply of glucose absorbed from the dialysis fluid. One common and important side effect of this treatment is weight gain and accumulation of body fat stores. However, not all patients accumulate body fat mass during PD, and the reason for this is not clear. Recently, two new mitochondrial uncoupling proteins (UCP2 and UCP3) have been found to have thermogenic properties that suggest involvement in the control of metabolic efficiency in humans. Moreover, recent results suggest that a polymorphism in the UCP2 gene may contribute to adipose tissue accumulation through its effects on energy metabolism. It could therefore be speculated that genetic differences in the metabolic rate might contribute to the differences in the accumulation of fat tissue during PD.

Genotyping of a polymorphism in the 3' untranslated region of exon 8 of UCP2 was performed in 41 patients (53 +/- 2 years) with chronic renal failure for whom we had prospective data on body composition (as estimated by dual-energy x-ray absorptiometry) following PD. In addition, indices of dialysis adequacy, peritoneal glucose absorption, and urea kinetics were followed (3 to 6 times per year in each patient) during treatment with PD. The degree of physical activity was assessed before the start of PD.

Twenty patients with the deletion/deletion UCP2 genotype had a significant increase in body weight (3.0 +/- 0.8 vs. -1.0 +/- 1.1 kg, P < 0.01) and body fat mass (3.8 +/- 0.9 vs. 0.8 +/- 1.0 kg, P < 0.05) during PD, compared with 19 patients with an insertion/deletion UCP2 genotype. On the other hand, no significant differences in indices of dialysis adequacy, peritoneal glucose absorption, urea kinetic parameters, or degree of physical activity were observed when comparing patients who accumulated or lost fat tissue during PD.

As most patients with the deletion/deletion UCP2 genotype acquired fat tissue during PD, the present results suggest that the UCP2 polymorphism contributes to variations in body composition. Thus, variations in UCP2 production or activity may be factors contributing to adipose tissue accumulation in a subgroup of patients treated with PD. It is possible that the polymorphism has a similar effect in the general population.