Novel Insights in the Physiopathology and Management of Obesity-Related Kidney Disease

Abstract

Obesity is recognized as an independent risk factor for the development of kidney disease, which has led to the designation of obesity-related glomerulopathy (ORG). Common renal features observed in this condition include glomerular hypertrophy, glomerulosclerosis, haemodynamic changes and glomerular filtration barrier defects. Additionally, and although less studied, obesity-related kidney disease also involves alterations in renal tubules, including tubule hypertrophy, lipid deposition and tubulointerstitial fibrosis. Although not completely understood, the harmful effects of obesity on the kidney may be mediated by different mechanisms, with alterations in adipose tissue probably playing an important role. An increase in visceral adipose tissue has classically been associated with the development of kidney damage, however, recent studies point to adipose tissue surrounding the kidney, and specifically to the fat within the renal sinus, as potentially involved in the development of ORG. In addition, new strategies for the treatment of patients with obesity-related kidney disease are focusing on the management of obesity. In this regard, some non-invasive options, such as glucagon-like peptide-1 (GLP-1) receptor agonists or sodium–glucose cotransporter-2 (SGLT2) inhibitors, are being considered for application in the clinic, not only for patients with diabetic kidney disease but as a novel pharmacological strategy for patients with ORG. In addition, bariatric surgery stands as one of the most effective options, not only for weight loss but also for the improvement of kidney outcomes in obese patients with chronic kidney disease.

Inhibition of the mTORC1 pathway alleviates adipose tissue fibrosis

“…In the future, we will explore the roles of mTORC1 in adipose fibrosis caused by ageing and other factors that are still unclear. In addition, the ectopic adipose deposition caused by obesity causes fibrosis of the liver, kidney [ 31 , 32 ], and other organs. In this study, we mainly discuss the role of mTORC1 in the fibrosis of adipose tissue itself.…”

Bariatric Surgery Outcomes in Patients with Chronic Kidney Disease

“…Actually, several observational studies have analyzed kidney outcomes in patients with or without CKD who undergo BS [ 9 , 34 , 35 , 36 ]. Overall, results have consistently shown that BS is associated with slower eGFR decline [ 8 , 9 , 37 , 38 , 39 ]. In line with these findings, patients in our cohort experienced an improvement in eGFR in the short and medium term.…”

“…Recent studies point to a connection between lipotoxicity and CKD. Moreover, adipose tissue depots directly related to the kidney (renal sinus fat) might also play a role [ 39 ].…”

Emerging roles of proximal tubular endocytosis in renal fibrosis

“…It is believed that megalin could be a therapeutic target for obesity-related CKD. In obesity-related renal disease, numerous factors contribute to the development and progression of CKD, including insulin resistance, lipotoxicity, dysregulation of adipocytokine secretion, contribution of different fat depots, etc., ( Sandino et al, 2022 ). Endocytosis impairment in tubule may partially contribute to CKD progression.…”