These factors are also corrected by TZD treatment in ZDF rats, via mechanisms that require further studies. Together, our experiments in rodents and in cultured cells support the hypothesis that renal steatosis may be one sellckchem of the factors responsible for unduly acidic urine in the metabolic syndrome. In addition, our findings raise the possibility that treatment with PPAR�� agonists could reduce renal fat accumulation, having as one consequence improved urinary acidification and, in humans, decreased risk for uric acid stone formation. Renal steatosis and the antisteatotic action of TZD in the kidney are likely to have multiple effects beyond urinary acidification.

Several lines of evidence in both humans and animal models have associated TZD treatment with surrogate markers of renal protection in type 2 diabetes and the metabolic syndrome (3, 23, 30, 56), but whether this effect is at least in part due to decreased steatosis in the kidney requires further exploration. Importantly, whether humans accumulate fat in the kidney and whether renal steatosis causes damage in a similar fashion are currently unknown. A comprehensive approach to renal steatosis is required to establish its importance in human pathophysiology, including experiments aimed to characterize its correlation with systemic disease and its effects on various aspects of renal function, including but not limited to urinary acidification. GRANTS This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants P01-DK-020543, R01-DK-48482 and R01-DK-081423 and by a grant from the Simmons Family Foundation (to O.

W. Moe). These studies utilized the Biomedical Cores of the O’Brien Kidney Center (P30-DK-079328). I. A. Bobulescu was supported by a Fellowship Grant from the National Kidney Foundation, by a Seed Grant from the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, and by the Carl W. Gottschalk Research Scholar Award from the American Society of Nephrology. ACKNOWLEDGMENTS The authors are grateful to Dr. Roger Unger for expert advice and for generously providing ZDF rats and to Janice Koska, Kathy Rodgers, Alan Stewart, and Anthony Nguyen for technical assistance.
A 61-year old man presented with a left upper quadrant abdominal mass after experiencing several intermittent episodes of nausea, vague abdominal discomfort, and mild acid reflux. He also reported a nine kilogram weight loss over the prior six to eight months. Physical Brefeldin_A examination revealed a large mass in his upper abdomen. Abdominal computed tomography (CT) revealed a 21 �� 12 cm heterogeneous mass occupying his mid and left upper quadrants (Figure (Figure1).1). Based on its location and imaging characteristics, the mass was hypothesized to be a GIST.