Background: Obesity is a global epidemic associated with risk factors for chronic kidney disease (CKD). The Action for Health in Diabetes (Look AHEAD) trial showed greater weight loss after exposure to intensive lifestyle intervention compared to diabetes support and education (i.e., usual care). Weight loss interventions can improve short-term kidney outcomes, but larger longitudinal studies on non-surgical obesity treatments are needed. We investigated the effects of weight loss from lifestyle modifications on kidney function over ten years. Methods: We performed a retrospective cohort study of 4,901 individuals with type 2 diabetes and BMI ≥25kg/m2 using the Look AHEAD dataset which was collected between 2001-2015. We used linear mixed effect models to evaluate for within-individual changes of mean values and slope of estimated glomerular filtration rate (eGFR) (primary outcome) and urine albumin to creatinine ratio (UACR) (secondary outcome) between randomization arms. We evaluated for effect modification by baseline kidney function and visit year using the Wald test and a two-sided significance level of 0.05. Results: At baseline, mean eGFR in both randomization arms was 89ml/min/1.73m2 and 83% of participants had normal albuminuria. Over 10 years, the intervention arm had a slightly higher mean eGFR compared to the usual care arm (beta-coefficient (B): 0.5, p=0.04). The intervention improved loss of eGFR after year two (B: 0.78, pinteraction=0.001). The magnitude of the intervention''''''''s effect differed by year with the slowest decline in eGFR by 1.20ml/min/1.73m2 (p=0.002) at year 3. Among individuals with a baseline eGFR <80ml/min/1.73m2, the mean eGFR in the intervention arm was 1.25ml/min/1.73m2 (p=0.02) higher than the usual care arm. However, there was no difference in mean UACR (B: -0.001, p=0.94) or slope of UACR (B: 0.0002, p=0.80) between arms. Conclusion: Among individuals at high risk for CKD, exposure to intensive lifestyle intervention resulted in slower eGFR loss by year 2 and slightly higher kidney function over 10 years compared to usual care. Individuals with lower kidney function had greater benefit from the intervention than those with higher kidney function. Future longitudinal studies studying the effect of lifestyle modifications in individuals with excess body weight and reduced kidney function may support its use to treat kidney disease.