Various non-mutually exclusive and partly overlapping mechanisms

The mechanisms by which Rolipram obesity can directly contribute to increased CKD and ESRD risk, independent of its association with hypertension and type 2 diabetes, are incompletely understood. Various non-mutually exclusive and partly overlapping mechanisms have been proposed, including inflammation, hyperfiltration, podocyte stress, oxidative stress, changes in various hormones or signaling molecules such as leptin and adiponectin, as well as renal lipid accumulation and lipotoxicity. In addition to its association with CKD and ESRD, obesity has been linked with increased risk for kidney stones in general, and uric acid stones in particular. While the pathophysiology of uric acid nephrolithiasis is likely multifactorial, animal and cell culture experiments have shown that lipid accumulation in proximal tubule cells may contribute to the urinary biochemical abnormalities that underpin uric acid stone risk. Lipid accumulation in other organs, including skeletal Sulfamethoxypyridazine muscle, myocardium, pancreas and liver, has been associated with obesity in humans, and has been implicated in cell and organ dysfunction. Lipid accumulation in the kidney has been described in a number of animal models, but very little human data are available. In particular, establishing whether renal lipid accumulation occurs in humans with increased BMI, thus potentially contributing to obesity-related CKD, ESRD and nephrolithiasis risk, is of fundamental importance, and there is no database on this topic. To address this knowledge gap, we measured renal triglycerides and defined their localization in normal kidney surgical specimens obtained from patients undergoing nephrectomy, with a wide range of BMI. In addition, we measured tissue levels of 16 common ceramide species in representative samples. Lipid accumulation with increasing BMI has been described in multiple non-adipose tissues, including the liver, pancreas, myocardium and skeletal muscle.With some exceptions, such as the ����athlete��s paradox���� of high intramuscular lipid associated with marked insulin sensitivity in endurancetrained athletes, lipid accumulation has been associated with lipotoxicity and organ dysfunction.