Improvements in diabetic albuminuria and podocyte differentiation following Roux-en-Y gastric bypass surgery

Abstract

Background: Multiple studies demonstrate an albuminuria-lowering impact of Roux-en-Y gastric bypass surgery, but neither evaluation of its penetrance across different baseline levels of albuminuria nor its association with alterations in podocyte phenotype has previously been reported. Methods: We profiled changes in body weight, glycaemic control and urinary albumin excretion following Roux-en-Y gastric bypass surgery in 105 patients with type 2 diabetes, albuminuria of varying degrees of severity and classified as being at moderate or high risk of chronic kidney disease progression according to the Kidney Disease: Improving Global Outcomes 2012 criteria. In parallel pre-clinical studies, the impact of Roux-en-Y gastric bypass surgery on markers of podocyte injury was assessed in the Zucker diabetic fatty rat model of diabetic kidney disease. Results: At 12- to 18-month post-operative follow-up in patients at moderate or high risk of chronic kidney disease, significant reductions in albuminuria were observed across all tertiles of baseline albumin–creatinine ratio, with remission of albuminuria occurring in 78% of patients. Relative to sham-operated control animals, weight loss and improvements in glycaemia following Roux-en-Y gastric bypass surgery in Zucker diabetic fatty rats were paralleled by normalisation of glomerular tuft-size, reductions in podocyte expression of desmin, and preservation of podocyte foot process morphology. Conclusion: Improvements in podocyte differentiation likely underpin the reductions in albuminuria observed following Roux-en-Y gastric bypass surgery.

Characterization of the renal cortical transcriptome following Roux-en-Y gastric bypass surgery in experimental diabetic kidney disease

“…We corroborated our previous findings regarding the beneficial impact of RYGB on the cardinal biochemical, structural and ultrastructural features of experimental DKD in the ZDF rat. 21 22 We sought then to describe both the transcriptional landscape in the kidneys of ZDF SHAM rats, the changes to that landscape arising secondary to RYGB and how these changes correlated with structural and ultrastructural indicators of renal injury.…”

“…Under isoflurane anesthesia, a midline laparotomy and mobilization of the gut was performed as SHAM surgery. According to standard protocol, 21 22 in RYGB-operated rats the proximal jejunum was transected 12 cm from the pylorus and a side-to-side jejuno-jejunal anastomosis created leaving a common channel of 30 cm. A small gastric pouch was created and end-to-end anastomosed to the alimentary limb.…”

“… 19 20 We have previously reported that RYGB effectively reduces albuminuria in the Zucker diabetic fatty (ZDF) rat in conjunction with evidence of improvements in glomerular histology and ultrastructure. 21 22 …”

Metabolic Surgery to Treat Obesity in Diabetic Kidney Disease, Chronic Kidney Disease, and End-Stage Kidney Disease; What Are the Unanswered Questions?

“…Canney et al investigated the impact of RYGB in addition to optimal medical therapy in 105 individuals with type 2 diabetes (mean duration 13 ± 3 years) and moderately or severely increased albuminuria ( 77 ). At mean 13-month follow-up, mean BMI reduced from 38 to 27 kg/m 2 , mean HbA 1c decreased from 8 to 6%, and median uACR decreased by 81% from 88 to 14 mg/g.…”

Obesity is common in chronic kidney disease and associates with greater antihypertensive usage and proteinuria: evidence from a cross‐sectional study in a tertiary nephrology centre

“…Reducing the severity of obesity with metabolic surgery decreases the incidence of albuminuria and end‐stage kidney disease (ESKD) over long‐term follow‐up 5‐7 . In a single‐centre study of 105 individuals with type 2 diabetes and albuminuria who underwent gastric bypass surgery, median reductions in albuminuria of 80.7% were achieved over mean 13‐month follow‐up 8 . Postoperative reductions in proteinuria occur independently of improvements in blood pressure and metabolic control, suggesting that weight‐ and glycaemia‐independent mediators may contribute to the renoprotective effects of the procedure 9,10 .…”