Obesity’s Double Role in CKD as Comorbidity and Driver

As obesity and chronic kidney disease (CKD) continue to rise as global clinical challenges, the intersection between excess weight and kidney function has become increasingly important to patient outcomes and disease progression.1

To discuss the association between excess adiposity, defined as a body mass index (BMI) ≥30 kg/m², and impaired renal function, HCPLive spoke with 2 experts in nephrology to glean insights relevant to clinical practice.

Each kidney contains a finite number of nephrons, ranging from approximately 200,000 to 2 million per kidney. As body mass increases, metabolic demand rises, prompting compensatory increases in glomerular capillary pressure, intraglomerular flow, and single-nephron glomerular filtration. Over time, this sustained hyperfiltration places mechanical stress on the glomerulus, contributing to podocyte injury, glomerulosclerosis, proteinuria, and progressive nephron loss. Obesity itself has been independently linked to these pathophysiological changes, even after accounting for common comorbidities such as diabetes and hypertension.1

This physiologic strain becomes more pronounced at increased levels of adiposity, where obesity may contribute directly to renal injury beyond hyperfiltration alone.1

“Severe obesity, like a BMI above 40, can also lead to nephron loss itself because of the inflammatory effects obesity has on the body,” explained Holly Kramer, MD, a nephrologist at Loyola University Medical Center and editor in chief of Advances in Kidney Disease and Health.1

The inflammatory burden associated with severe obesity may help explain why individuals with higher BMI often experience more rapid CKD progression, even in the absence of advanced disease at baseline.1

Clinical trial populations have also highlighted the frequent coexistence of impaired kidney function and elevated BMI. Vlado Perkovic, MBBS, PhD, the provost at the University of New South Wales and an investigator in the FLOW trial, has observed this pattern firsthand.2,3

FLOW, which evaluated kidney outcomes in adults with type 2 diabetes (T2D) and CKD, was not designed as a weight-loss study and did not include BMI-based eligibility criteria. Participants were enrolled based on kidney disease parameters, including an estimated glomerular filtration rate (eGFR) of 25–75 mL/min/1.73 m² and a urine albumin-to-creatinine ratio (UACR) of >300–<5000 mg/g, or 100–5000 mg/g among those with an eGFR of 25–<50 mL/min/1.73 m². Notably, a quarter of patients had a BMI <27 in the FLOW trial.2

Despite this, the mean BMI of participants in the FLOW trial was 32. Similarly, the CREDENCE trial, which also did not focus on weight loss, reported an average BMI of 31. This highlights obesity as a prevalent, rather than incidental, comorbidity in contemporary CKD populations. Taken together, these findings underscore the importance of considering body weight as a core component of CKD risk assessment, rather than a secondary concern.2,3

“What that tells us is that people with diabetes and kidney disease, on average, are very overweight,” said Perkovic. “And certainly are likely to benefit from weight loss as well. These are wonderful treatments that help address multiple sorts of parallel pathologies that are developing in many of our patients, and it's exciting to think about the future and whether some of the more potent agents that produce even more weight loss might.”

References

1. Kramer H. Utilizing diet to prevent obesity, preserve kidney function, with Holly Kramer, MD. HCPLive. January 30, 2026. https://www.hcplive.com/view/utilizing-diet-prevent-obesity-preserve-kidney-function-holly-kramer-md. Accessed January 31, 2026.

2. Rossing P, Baeres FMM, Bakris G, et al. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrology Dialysis Transplantation. 2023;38(9). doi:https://doi.org/10.1093/ndt/gfad009

3. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. New England Journal of Medicine. 2019;380(24):2295-2306. doi:https://doi.org/10.1056/nejmoa1811744