There is a pressing need to develop biomarkers for renal disease, which might assist in diagnosis and prognosis and might provide endpoints for clinical trials of drugs designed to slow progression of renal insufficiency. We propose to study potential biomarkers in five populations. First, we will study remittive therapy for glomerular disease (sample size up to 40), enrolling children with idiopathic nephrotic syndrome (N=20) and adults with minimal change, focal segmental glomerulosclerosis, and collapsing glomerulopathy (N=20). We will collect periodic urine samples as these patients receive remittive therapy with glucocorticoids or other agents. We will also study up to 10 healthy adult volunteers. We will carry out targeted urine proteomic studies, measuring levels of glomerular cell markers and cytokines, and we will profile urine proteins using mass spectrometry. Our goals are to identify markers of particular disease entities and of steroid responsiveness and to explore whether biomarkers contribute to the histologic sub-classification of these diseases. Second, we will study up to 40 adults with progressive chronic kidney disease of various etiologies and glomerular filtration rate <60 ml/min/1.73m2. We will study blood and urine samples, using both targeted and profiling approaches. Our goal is to identify biomarkers that correlate with progressive loss of glomerular filtration function, which is a functional correlate of progressive renal fibrosis. Third, we will study up to 40 adults, primarily with diabetic nephropathy, who start or stop angiotensin antagonist therapy (angiotensin converting enzyme inhibitors or angiotensin receptor blockers) and compare urine proteomic profiles on therapy and off therapy (4 week interval). Our goal is to identify potential biomarkers that correlate with the beneficial anti-fibrotic effects of these agents. Fourth, we wish to define possible sex differences in urine exosome proteins, obtained from healthy volunteers, who are hospitalized for six days for administration of a standard diet and collection of research urine samples. Fifth, we wish to determine whether salt intake influences urine exosome proteins, obtained from healthy volunteers. These subjects will be hospitalized for 12 days during which time they will be placed sequentially on a high salt diet and a low salt diet, with collection of research urine samples and blood pressure monitoring. Proteomic analysis in these studies will take several approaches, including mass spectrometry of urinary peptides, analysis of urinary exosomes, and immunologic detection and quantification of candidate proteins in urine and blood.