The objective of this application is to describe a pilot study to evaluate the efficacy of alternate-day prednisone in the treatment of IgA nephropathy (IgAN) in children, adolescents, and young adults. Details of the study design, administration, and statistical analysis are provided. Although IgAN is a disorder of the kidneys that was first described in France in 1967, none of the current treatment options are of proven benefit. Over the past few years, a number of small studies have suggested that prednisone is beneficial, but none of these have been definitive. The lack of proven therapy for IgAN is of concern because it is now apparent that untreated IgAN progresses to end-stage renal disease in up to 50% of patients and is a significant contributor to the total ESRD population in the United States. The proposed pilot study is a multicenter, double-blind, placebo- controlled, randomized clinical trial of the efficacy and safety of 2 years of therapy with alternate-day prednisone in approximately 90-100 children, adolescents, and young adults with moderately severe IgAN. Since we have defined rather strict criteria for patient entry into this trial, the number of eligible patients in individual nephrology centers will be small. Hence, a large number of centers (34) will be participating in order to recruit sufficient patients for valid statistical analysis. In order to successfully complete this study, it is essential that the activities of the 34 centers are carefully coordinated. This will be achieved through the Administration Center of the Southwest Pediatric Nephrology Study Group (SPNSG), a collaborative group that has been studying various aspects of IgAN for 14 years. To handle the complexities of this multicenter, clinical trial, we will establish rigorous procedures for monitoring medication administration and patient compliance, data management and analysis, clinical and laboratory measurements, and will maintain close communication with the 34 participating centers. Results from this 3-year pilot study will be analyzed by members of an experienced Data and Statistics Core in Birmingham, Alabama. From these pilot data, we will determine if a full- scale clinical trial is justified and feasible. if this is the case, a competitive renewal application will be submitted to the NIH.