Individuals with isolated medical abnormalities (IMAs) are undergoing living donor nephrectomy more frequently. Knowledge of health risks for these living donors is important for donor selection, informed consent and follow-up. We systematically reviewed studies with > or = 3 living kidney donors with preexisting IMAs, including older age, obesity, hypertension, reduced glomerular filtration rate (GFR), proteinuria, microscopic hematuria and nephrolithiasis. We abstracted data on study and donor characteristics, perioperative outcomes, longer term renal and blood pressure outcomes and mortality and compared them to those of non-IMA donors. We found 22 studies on older donors (n = 987), 10 on obese donors (n = 484), 6 on hypertensive donors (n = 125), 4 on donors with nephrolithiasis (n = 32), 2 on donors with microscopic hematuria and one study each on donors with proteinuria or reduced GFR. Perioperative outcomes for donors with and without IMAs were similar. Few studies reported longer term (> or = 1 year) rates of hypertension, proteinuria or renal function. Studies were frequently retrospective and without a comparison group. Given the variability among studies and their methodological limitations, uncertainties remain regarding long-term medical outcomes for IMA donors. As transplant centers continue to cautiously screen and counsel potential IMA donors, rigorously conducted, longer term prospective cohort studies are needed.