Renal risks of an emerging "epidemic" of obesity: The role of adipocyte-derived factors

Obesity has reached epidemic proportions in the affluent societies of the world, especially during the last two decades. Recently, there has been growing awareness and concern regarding rapidly emerging renal complications of obesity. It appears to play a central contributory role in the genesis of systemic hypertension, nephrotic-range proteinuria with focal segmental glomerulosclerosis (FSGS), and renal cell carcinoma, apart from the likely impact that the obesity has on the outcomes of patients on long-term dialysis and those with renal transplants. Obesity-related FSGS has characteristic clinicopathological features, i.e., minimal clinical edema and more or less normal levels of serum albumin, cholesterol, and blood pressure. It may progress to end-stage renal disease (ESRD) in about 50% of cases. In addition, severe obesity may enhance the progression to ESRD of preexisting nephropathies such as IgA nephropathy. The likely pathophysiology of obesity-associated nephropathy may include increased renal venous pressure, hyperfiltration glomerular injury, glomerular hypertrophy, hyperlipidemia, and increased synthesis of vasoactive and fibrogenic substances, including angiotensin II, prostaglandin I-2alpha, insulin, leptin, tumor necrosis factor-alpha, and transforming growth factor-beta 1, all of which are adipocyte-derived factors. Strategies such as weight reduction early in the course of the disease, in conjunction with the judicious use of angiotensin-converting enzyme inhibitors and possibly statins, might improve the outcome of obesity-related hypertension and nephropathy. However, the impact of obesity on the outcome of patients on long-term dialytic therapy and of those undergoing renal transplantation remains largely uncertain.