Project 1. Our preliminary studies have shown that inflammation, oxidative stress, and endothelial dysfunction are evident in patients with chronic kidney dysfunction (CKD). At the current time, there is an immediate need for specific and sensitive biomarkers that can predict disease progression and stratify patients to those at risk to progress faster. With no approved treatment, control of hypertension and management of secondary features of chronic renal insufficiency are present clinical measures to slow the progression of disease. Project 2: Calcineurin inhibitors are highly effective immunosuppressants used in patients with immune diseases and after transplantation. However, their use is limited by their toxic effects on the kidney and the induction of vascular endothelial dysfunction. Current clinical diagnostic markers are known to be insensitive and to only rise after significant damage has already occurred. The proposed study seeks to establish that the negative effects of the calcineurin inhibitor tacrolimus on kidney and vascular endothelial cells in adult and pediatric patients with nephrotic syndrome and after kidney transplantation are reflected by changes in plasma and urine metabolite and protein pattern changes and that these changes have better sensitivity and specificity compared to markers currently established in the clinic such as creatinine in serum.