Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Dublin, Ireland,
Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Dublin, Ireland.
Nephron. 2021;145(6):585-594. doi: 10.1159/000511790. Epub 2020 Dec 2.
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).
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.
肥胖和 2 型糖尿病的手术治疗方法，尤其是 Roux-en-Y 胃旁路（RYGB）手术，已被证明具有肾脏保护作用，在肥胖患者中，经过 15 至 20 年的随访，可降低白蛋白尿和终末期肾病的发生率。代谢手术对糖尿病肾病患者肾脏的组织水平影响在临床样本中不易检测。然而，从糖尿病肾病（DKD）啮齿动物模型的一系列临床前研究中，现在已经阐明了代谢手术对肾脏保护作用的细胞和分子基础。
实验性代谢手术（RYGB、袖状胃切除术[SG]、Roux-en-Y 食管空肠吻合术和十二指肠空肠旁路术）在 DKD 大鼠模型中表现出明显的降低白蛋白尿作用。在 Zucker 糖尿病肥胖大鼠中进行 RYGB 后，肾小球组织学得到改善，表现为足细胞应激、肾小球肥大和肾小球硬化减少。RYGB 和 SG 后肾小球超微结构得到改善，表现为足细胞足突融合的可量化减少。这些结构改善的潜在途径水平的转录程序已通过 RNA 测序进行了描述，与炎症和纤维化反应的激活显著降低有关。
实验性代谢手术可降低 DKD 的生化、组织学和分子指标。这些临床前数据支持了人们对代谢手术作为肥胖和 DKD 患者减缓肾功能下降的潜在治疗方法的兴趣日益增加。
