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

Abstract

Obesity is a major factor in contemporary clinical practice in nephrology. Obesity accelerates the progression of both diabetic and non-diabetic chronic kidney disease and, in renal transplantation, both recipient and donor obesity increase the risk of allograft complications. Obesity is thus a major driver of renal disease progression and a barrier to deceased and living donor kidney transplantation. Large observational studies have highlighted that metabolic surgery reduces the incidence of albuminuria, slows chronic kidney disease progression, and reduces the incidence of end-stage kidney disease over extended follow-up in people with and without type 2 diabetes. The surgical treatment of obesity and its metabolic sequelae has therefore the potential to improve management of diabetic and non-diabetic chronic kidney disease and aid in the slowing of renal decline toward end-stage kidney disease. In the context of patients with end-stage kidney disease, although complications of metabolic surgery are higher, absolute event rates are low and it remains a safe intervention in this population. Pre-transplant metabolic surgery increases access to kidney transplantation in people with obesity and end-stage kidney disease. Metabolic surgery also improves management of metabolic complications post-kidney transplantation, including new-onset diabetes. Procedure selection may be critical to mitigate the risks of oxalate nephropathy and disruption to immunosuppressant pharmacokinetics. Metabolic surgery may also have a role in the treatment of donor obesity, which could increase the living kidney donor pool with potential downstream impact on kidney paired exchange programmes. The present paper provides a comprehensive coverage of the literature concerning renal outcomes in clinical studies of metabolic surgery and integrates findings from relevant mechanistic pre-clinical studies. In so doing the key unanswered questions for the field are brought to the fore for discussion.

Keywords: chronic kidney disease; diabetic kidney disease; dialysis; end-stage kidney disease; kidney transplantation; metabolic surgery; obesity; type 2 diabetes mellitus.

Figure 1

Overview of the four principal metabolic surgery types. AGB, adjustable gastric banding; BPD/DS, biliopancreatic diversion with duodenal switch; RYGB, Roux-en-Y gastric bypass surgery; VSG, vertical sleeve gastrectomy. (A) vertical sleeve gastrectomy; (B) Roux-en-Y gastric bypass surgery; (C) adjustable gastric banding; (D) biliopancreatic diversion with duodenal switch.

Figure 2

Overview of mechanisms underpinning weight loss, improved glycaemia, and renoprotection after metabolic surgery. RYGB is depicted in the figure as more mechanistic data supports its weight loss, glycaemic, and renoprotective benefits compared with other metabolic surgery procedures. FGF-19, fibroblast growth factor-19; GLP-1, glucagon-like peptide-1; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; NAFLD, non-alcoholic fatty liver disease; OXY, oxyntomodulin; PYY, peptide YY; TGs, triglycerides. Figure 2 was created by adapting images downloaded from the image bank of Servier Medical Art (https://smart.servier.com/). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (CC BY 3.0: https://creativecommons.org/licenses/by/3.0/).

Figure 3

Potential roles of metabolic surgery in facilitating access to kidney transplantation and improving allograft outcomes in people with obesity and end-stage kidney disease. Although not visually represented, pre-transplant laparoscopic metabolic surgery has been successfully performed in people on peritoneal dialysis without necessitating temporary haemodialysis. However, reports to date are limited and further study is warranted to determine surgical and dialysis complication rates in this population. Figure 3 was created by adapting images downloaded from the image bank of Servier Medical Art (https://smart.servier.com/). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (CC BY 3.0: https://creativecommons.org/licenses/by/3.0/).