Gastric bypass vs. 'Medical Bypass' - Impact on experimental diabetic kidney disease

Albuminuria is significantly reduced following Roux-en-Y gastric bypass (RYGB) surgery, suggesting a renoprotective effect of the intervention. Herein, we assess the relative impact of RYGB and RYGB equivalent non-surgical weight loss and glycaemic improvement on glomerular injury and global renal transcriptomic responses in the Zucker diabetic fatty rat (ZDF) model of diabetic nephropathy. We coined the term "medical bypass" (MB) to describe the intensive diet and pharmacotherapy based non-surgical intervention Adult ZDF rats underwent sham surgery (n=15) or RYGB (n=9). Nine sham-operated rats were calorie restricted and received insulin, liraglutide, metformin, ramipril, rosuvastatin and fenofibrate for 2 months (MB). Zucker fa/+ rats acted as healthy controls throughout. Bodyweight, glycaemia, albuminuria and glomerular injury specifically podocyte number, density and ultrastructure were assessed at follow up. Renal transcriptomes were compared by RNA-seq. RYGB resulted in 20-30% weight loss, normalized glycaemia and albuminuria and reduced indices of glomerular injury, specifically podocyte injury (foot process effacement). RYGB equivalent outcomes were obtained on all parameters following MB. Overall design: RNA-seq was performed to identify the renal transcriptomic profile of kidney disease in the ZDF rat, and to investigate the relative effects of Medical bypass intervention on the renal transcriptome. N=9 replicates were profiled.