Weight loss interventions for overweight or obese individuals with chronic kidney disease (CKD): a systematic review and meta-analysis

Obesity and chronic kidney disease (CKD) are two major health problems worldwide, highly intertwined with one another, with an increasing prevalence in recent years. Many studies have shown that obesity is associated not only with the onset but also with the progression of CKD. In the past decades, several weight loss interventions have been developed, including non-pharmacological measures such as lifestyle changes, pharmacological interventions, as well as bariatric surgery techniques. However, to date, it is unclear whether these interventions are safe for those patients and efficient in reducing renal and overall cardiovascular risk. A systematic search of PubMed and CENTRAL databases was performed up to August 2025. Randomized clinical trials evaluating the effectiveness and/or safety of any weight-loss interventions (lifestyle, pharmacological, and surgical approaches) in overweight (BMI 25–29.9 kg/m²) or obese (BMI ≥30 kg/m²) adult patients with any stage of CKD (pre-dialysis, dialysis, kidney transplantation) were included. Primary endpoints were kidney outcomes (estimated glomerular filtration rate and albuminuria/proteinuria) and cardiovascular outcomes and mortality; secondary endpoints included anthropometric parameters (change in body weight, body mass index and waist circumference) and blood pressure (systolic and diastolic). Data were extracted independently by two authors using predefined forms. The RoB 2 tool from the Cochrane Handbook was used to assess the risk of bias of the included studies. Due to significant heterogeneity, a random effects model was applied for the meta analysis. Results were expressed as mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes. Additionally, a qualitative synthesis was performed when statistical data could not be pooled. From 24,553 identified records, 39 studies (n=10,928) were included in qualitative and 27 (n=7,015) in quantitative analysis. Cardiovascular outcomes and mortality were insufficiently reported and could not be pooled. With regards to the other endpoints, eGFR demonstrated a non-significant upward trend following lifestyle and pharmacological interventions (GLP-1 based therapies), and a significant increase following bariatric surgery (MD 6.09 ml/min/1.73 m²; 95% CI [3.66, 8.52], I2=1%). Pharmacological interventions were associated with a significant reduction in albuminuria, with a 41% relative decrease in urine albumin-to-creatinine ratio compared with placebo (95% CI 29%, 52%; I²=86%). Anthropometric parameters, including body weight, BMI, and waist circumference, improved across all intervention categories, with lifestyle-based approaches being the most extensively studied (weight loss MD –4.13 kg; 95% CI [–6.49, –1.76], I2=83%). Systolic and diastolic BP showed modest, non-significant reductions following lifestyle interventions compared with usual care (for SBP: MD −3.10mmHg; 95% CI −7.59 to 1.38, I2=45%), while data for pharmacological and surgical approaches were limited and conclusions cannot be made. To conclude, in patients with CKD and overweight or obesity, all types of interventions (lifestyle, pharmacological, surgical) are effective for weight loss, associated with a trend toward increased eGFR after the intervention. GLP-1–based therapies confer additional nephroprotective effects by significantly reducing albuminuria. Uncertainty persists for the remaining outcomes, highlighting the need for additional research.