Effect of Roux-en-Y gastric bypass and diet-induced weight loss on diabetic kidney disease in the Zucker diabetic fatty rat

Background: Reductions in urinary protein excretion after Roux-en-Y gastric bypass (RYGB) surgery in patients with diabetic kidney disease have been reported in multiple studies.

Objectives: To determine the weight loss dependence of the effect of RYGB on urinary protein excretion by comparing renal outcomes in Zucker diabetic fatty rats undergoing either gastric bypass surgery or a sham operation with or without weight matching.

Setting: University laboratories.

Methods: Zucker diabetic fatty rats underwent surgery at 18 weeks of age. A subgroup of sham operated rats were weight matched to RYGB operated rats by restricting food intake. Urinary protein excretion was assessed at baseline and at postoperative weeks 4 and 12. Renal histology and macrophage-associated inflammation were assessed at postoperative week 12.

Results: Progressive urinary protein excretion was attenuated by both RYGB and diet-induced weight loss, albeit to a lesser extent by the latter. Both weight loss interventions produced equivalent reductions in glomerulomegaly, glomerulosclerosis, and evidence of renal macrophage infiltration.

Conclusion: Weight loss per se improves renal structure and attenuates renal inflammatory responses in an experimental animal model of diabetic kidney disease. Better glycemic control post-RYGB may in part explain the greater reductions in urinary protein excretion after gastric bypass surgery.