Background and objectives Concerns exist about deleterious renal effects of low-carbohydrate high-protein weight loss diets. This issue was addressed in a secondary analysis of a parallel randomized, controlled long-term trial. Design, setting, participants, and measurements Between 2003 and 2007, 307 obese adults without serious medical illnesses at three United States academic centers were randomly assigned to a low-carbohydrate highprotein or a low-fatweight-loss diet for 24months. Main outcomes included renal filtration (GFR) indices (serum creatinine, cystatin C, creatinine clearance); 24-hour urinary volume; albumin; calcium excretion; and serum solutes at 3, 12, and 24 months. Results Comparedwith the low-fat diet, low-carbohydrate high-protein consumptionwas associatedwithminor reductions in serum creatinine (relative difference, 24.2%) and cystatin C (28.4%) at 3 months and relative increases in creatinine clearance at 3 (15.8 ml/min) and 12 (20.8 ml/min) months; serum urea at 3 (14.4%), 12 (9.0%), and 24 (8.2%) months; and 24-hour urinary volume at 12 (438 ml) and 24 (268 ml)months.Urinary calcium excretion increased at 3 (36.1%) and 12 (35.7%)months without changes in bone density or clinical presentations of new kidney stones. Conclusions In healthy obese individuals, a low-carbohydrate high-protein weight-loss diet over 2 yearswas not associatedwith noticeably harmful effects on GFR, albuminuria, or fluid and electrolyte balance comparedwith a low-fat diet. Further follow-up is needed to determine even longer-term effects on kidney function. Copyright © 2012 by the American Society of Nephrology.