Impact of Metabolic Surgery on Renal Injury in Pre-Clinical Models of Diabetic Kidney Disease

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Title: Impact of Metabolic Surgery on Renal Injury in Pre-Clinical Models of Diabetic Kidney Disease
Authors: Martin, William P.le Roux, Carel W.Docherty, Neil G.
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Date: Nov-2021
Online since: 2021-11-29T12:33:38Z
Abstract: Background: Surgical approaches to the treatment of obesity and type 2 diabetes, most notably the Roux-en-Y gastric bypass (RYGB) procedure, have been shown to be renoprotective, reducing the incidence of albuminuria and end-stage kidney disease over 15- to 20-year follow-up in patients with obesity. The tissue level effects of metabolic surgery on the diabetic kidney are not easily interrogated in clinical samples. However, elucidation of the cellular and molecular basis for the renoprotective effects of metabolic surgery is now emerging from a body of pre-clinical work in rodent models of diabetic kidney disease (DKD). Summary: Experimental metabolic surgery (RYGB, sleeve gastrectomy [SG], Roux-en-Y oesophagojejunostomy, and duodenojejunal bypass) exerts a pronounced albuminuria-lowering effect in rat models of DKD. Following RYGB in the Zucker diabetic fatty rat, glomerular histology is improved as demonstrated by reductions in podocyte stress, glomerulomegaly, and glomerulosclerosis. Glomerular ultrastructure improves after RYGB and after SG, manifested by quantifiable reductions in podocyte foot process effacement. The transcriptional programme underpinning these structural improvements has been characterized at the pathway level using RNA sequencing and is associated with a significant reduction in the activation of inflammatory and fibrotic responses. Key Messages: Experimental metabolic surgery reduces biochemical, histological, and molecular indices of DKD. These pre-clinical data support a growing interest in the potential utility of metabolic surgery as a therapeutic approach to slow renal functional decline in patients with obesity and DKD.
Funding Details: Wellcome Trust
Type of material: Journal Article
Publisher: Karger
Journal: Nephron
Volume: 145
Issue: 6
Start page: 585
End page: 595
Copyright (published version): 2020 Karger
Keywords: ObesityType 2 diabetesDiabetic kidney diseaseChronic kidney diseaseAlbuminuriaMetabolic surgeryZucker diabetic fatty rats
DOI: 10.1159/000511790
Language: en
Status of Item: Peer reviewed
ISSN: 1660-8151
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Appears in Collections:Conway Institute Research Collection
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