The present protocol seeks to advance our understanding of glomerular diseases characterized by progressive glomerulosclerosis in the absence of established immune-mediated renal injury. To this end, we will enroll patients with primary podocytopathies (minimal change nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy) and diabetic nephropathy, as well as patients with the clinical diagnosis (prior to renal biopsy) with one of these conditions. The protocol has three modules, with two consents and two assents. There is no ceiling on patient recruitment for modules 1 and 2. We want to recruit 16 patients for module 3.

1. EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS: This protocol will serve as a screening protocol for specific treatment protocols. It will also allow us to provide second opinions about selected glomerular diseases, to collect research samples (blood, urine, and archival kidney tissue) and treat selected patients with renal disease using standard therapy. These studies will allow us to test particular hypotheses and may provide the opportunity to generate new hypotheses that could be tested in other protocols.
2. RESEARCH RENAL BIOPSY IN PATIENTS WITH GLOMERULOSCLEROSIS: We will carry out renal biopsy for research purposes (limited to previously-diagnosed collapsing glomerulopathy) or to obtain additional renal tissue for research from a biopsy performed for clinical indications (includes diagnosed or suspected minimal change nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy, diffuse mesangial sclerosis, and diabetic nephropathy). This tissue will be used for studies of the podocyte transcriptome, and other glomerular and tubular processes, and for studies to identify viral causes of primary podocyte diseases.
3. Obesity-Associated Kidney Disease. We will collaborate with Dr. Mona Khurana in studies of lean and obese young adults carried out at Children's National Medical Center. We will assist her in the measurements of iothalamate and para-aminnohippurate clearance, in order to determine glomerular filtration rate and renal plasma flow.

The present protocol seeks to advance our understanding of glomerular diseases characterized by progressive glomerulosclerosis in the absence of established immune-mediated renal injury. To this end, we will enroll patients with primary podocytopathies (minimal change nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy) and diabetic nephropathy, as well as patients with the clinical diagnosis (prior to renal biopsy) with one of these conditions. The protocol has three modules, with three consents and three assents. There is no ceiling on patient recruitment for modules 1 and 2. We want to recruit 16 patients for module 3.

1. EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS: This protocol will serve as a screening protocol for specific treatment protocols. It will also allow us to provide second opinions about selected glomerular diseases, to collect research samples (blood, urine, and archival kidney tissue) and treat selected patients with renal disease using standard therapy. These studies will allow us to test particular hypotheses and may provide the opportunity to generate new hypotheses that could be tested in other protocols.
2. RESEARCH RENAL BIOPSY IN PATIENTS WITH GLOMERULOSCLEROSIS: We will carry out renal biopsy for research purposes (limited to previously-diagnosed collapsing glomerulopathy) or to obtain additional renal tissue for research from a biopsy performed for clinical indications (includes diagnosed or suspected minimal change nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy, diffuse mesangial sclerosis, and diabetic nephropathy). This tissue will be used for studies of the podocyte transcriptome, and other glomerular and tubular processes, and for studies to identify viral causes of primary podocyte diseases.
3. OBESITY-ASSOCIATE KIDNEY DISEASE. We will collaborate with Dr. Mona Khurana in studies of lean and obese young adults carried out at Children's National Medical Center. We will assist her in the measurements of iothalamate and para-aminnohippurate clearance, in order to determine glomerular filtration rate and renal plasma flow.

• Module 1:EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS

InclusionCriteria: children of all ages and adults, including pregnant women, and impaired subjects, all with kidney disease. For pathogenetic studies, we will also include healthy volunteers, including children greater than 12 yrs of age and adults.

Module 2:RESEARCH RENAL BIOPSY

1. Clinically-indicated renal biopsy, with use of a portion of a second biopsy core for research.

   Inclusion Criteria: all adults or children with past renal biopsy which demonstrated a glomerulosclerotic disease or in all adults or children without prior renal biopsy and clinical suspicion of glomerulosclerotic disease.

   Exclusion Criteria: Pregnant women.

2. Clinically-indicated renal biopsy, obtaining a third biopsy core for research purposes.

   Inclusion Criteria: all adults with past renal biopsy which demonstrated a glomerulosclerotic disease or in all adult patients without prior renal biopsy and high pre-test likelihood of a glomerulosclerotic disease.

   Exclusion Criteria: Pregnant women, patients with a single kidney, impaired subjects, and children less than 18 yr.

3. Research renal biopsy, performed largely or exclusively for research purposes.

Inclusion Criteria: adults with collapsing glomerulopathy.

Exclusion Criteria: Pregnant women, patients with a single kidney, impaired subjects, and children less than 18 yr.

Module 3: RENAL FUNCTION AND STRUCTURE IN LEAN, OVERWEIGHT, AND OBESE YOUNG ADULTS

Inclusion Criteria: young adults aged 18 to 21, including lean young adults with BMI less than 25 kg/m2 and obese young adults with BMI greater than 30 kg/m2. Participants with a history of hyperlipidemias or high fasting glucose will still be eligible for the study as these co-morbidities are often consequence of being obese.

Exclusion Criteria: Young adults with proteinuria (random urine protein to creatinine ratio greater than 0.2, microalbuminuria (spot urine albumin to cretinine ratio greater than 20 mg/g), creatinine clearance less than 80 mL/min/1.73m2, chronic kidney disease, high blood pressure (systolic blood pressure greater than 140 and diastolic blood pressure greater than 90 on 3 blood pressure readings obtained at least one week apart), diabetes, and pregnant women.