BACKGROUND Little is known about the effect of weight loss/gain on kidney function. Analyses are complicated by uncertainty about optimal body surface indexing strategies for measured glomerular filtration rate (mGFR). METHODS Using data from the African-American Study of Kidney Disease and Hypertension (AASK), we determined the association of change in weight with three different estimates of change in kidney function: (i) unindexed mGFR estimated by renal clearance of iodine-125-iothalamate, (ii) mGFR indexed to concurrently measured BSA and (iii) GFR estimated from serum creatinine (eGFR). All models were adjusted for baseline weight, time, randomization group and time-varying diuretic use. We also examined whether these relationships were consistent across a number of subgroups, including tertiles of baseline 24-h urine sodium excretion. RESULTS In 1094 participants followed over an average of 3.6 years, a 5-kg weight gain was associated with a 1.10 mL/min/1.73 m(2) (95% CI: 0.87 to 1.33; P < 0.001) increase in unindexed mGFR. There was no association between weight change and mGFR indexed for concurrent BSA (per 5 kg weight gain, 0.21; 95% CI: -0.02 to 0.44; P = 0.1) or between weight change and eGFR (-0.09; 95% CI: -0.32 to 0.14; P = 0.4). The effect of weight change on unindexed mGFR was less pronounced in individuals with higher baseline sodium excretion (P = 0.08 for interaction). CONCLUSIONS The association between weight change and kidney function varies depending on the method of assessment. Future clinical trials should examine the effect of intentional weight change on measured GFR or filtration markers robust to changes in muscle mass.