Obesity-Related Impacts on Kidney Function

Obesity is now recognised as an independent driver of chronic kidney disease through a combination of haemodynamic, structural and metabolic processes. Excess adiposity promotes glomerular hyperfiltration and increased intraglomerular pressure, leading to glomerular hypertrophy and eventual sclerosis. Adipose‐derived mediators, including leptin, tumour necrosis factor–α and other adipokines, fuel a pro-inflammatory milieu that accentuates oxidative stress and endothelial dysfunction within the renal microvasculature. Lipid accumulation in proximal tubular cells and podocytes further disrupts cellular energy balance, contributing to tubular injury and proteinuria. Over time these changes translate into progressive decline in glomerular filtration rate (GFR), heightened risk of albuminuria and accelerated progression to end-stage renal disease. Globally, the rising prevalence of obesity has magnified the burden of kidney dysfunction, underscoring the importance of integrated strategies that combine lifestyle modification, targeted blood pressure control and emerging pharmacological interventions to mitigate renal risk.

Research from Nature Portfolio

Recent clinical trial evidence has extended the benefits of glucagon-like peptide-1 receptor agonist therapy to renal endpoints in people with overweight or obesity. In a large randomised study of once-weekly semaglutide, treatment reduced the incidence of major composite kidney outcomes—including sustained decline in estimated GFR (eGFR), onset of macroalbuminuria and initiation of kidney replacement therapy—by nearly a quarter compared with placebo over two years. The protective effect was most pronounced in participants with baseline eGFR below 60 ml min–1 1.73 m–2, where the slowing of eGFR decline exceeded 2 ml min–1 1.73 m–2. These findings suggest that weight-loss–independent metabolic actions of semaglutide, such as improved glomerular haemodynamics and reduced intrarenal inflammation, can confer direct renal protection in obese populations without established diabetes.

Obesity-Related Impacts on Kidney Function publication trend

The graph below shows the total number of articles in obesity-related impacts on kidney function across all publications each year (not limited to Nature Index journals).

Technical terms

Glomerular filtration rate (GFR): the volume of fluid filtered by the renal glomeruli per unit time, a key indicator of kidney function.

Estimated GFR (eGFR): a calculated approximation of GFR based on serum creatinine or cystatin C levels, adjusted for age, sex and body size.

Albuminuria: the presence of albumin in urine, reflecting increased glomerular permeability and early kidney damage.

Glomerular hyperfiltration: an elevated GFR above normal physiological levels, often an early adaptive response in obesity that predisposes to later injury.

Adipokines: signalling proteins secreted by adipose tissue that modulate inflammation, insulin sensitivity and vascular function, affecting renal health.

References

1. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nature Medicine (2024).
2. Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium. The BMJ (2019).
3. Obesity-Related Chronic Kidney Disease—The Role of Lipid Metabolism. Metabolites (2015).
4. Proximal Tubular Hypertrophy and Enlarged Glomerular and Proximal Tubular Urinary Space in Obese Subjects with Proteinuria. PLOS ONE (2013).
5. Obesity and chronic kidney disease: A current review. Obesity Science & Practice (2022).
6. A Nephrologist Perspective on Obesity: From Kidney Injury to Clinical Management. Frontiers in Medicine (2021).