Permeability Factor in Focal Segmental Glomerulosclerosis

INCLUSION CRITERIA: Patients with idiopathic focal segmental glomerulosclerosis on renal biopsy, including the following categories: A) Untreated FSGS B) Steroid-dependent FSGS C) Steroid resistant FSGS D) Recurrent FSGS, with functioning allograft E) FSGS in ESRD, receiving hemodialysis Adults greater than or equal to18 will be eligible for all studies. Children greater than 20 kilograms, will be eligible for all branches of the study except for treatment of steroid resistant FSGS with pirfenidone, as pirfenidone has not previously been administered to pediatric patients in any setting. Children less than 20 kilograms will be excluded from the study for the following reason: plasma exchange in patients less than 20 kilograms requires a red blood cell transfusion, which significantly increases the risk of the procedure by exposing the patient to the risk of transfusion associated infections, and the safety of an aggressive course of plasma exchange has not been established in this population. EXCLUSION CRITERIA: Secondary FSGS: HIV-associated FSGS or hyperfiltration FSGS, including FSGS associated with congenital renal abnormalities, renal mass reduction, reflux nephropathy, interstitial nephritis, and sickle cell anemia are excluded. Patients with disease associated with immunosuppression, other than chronic renal failure. The presence of malignancy or the history of other serious, complicating illness such as myocardial infarction or cerebrovascular accident in the past six months, at the discretion of the investigators. For plasma exchange: A Department of Transfusion Medicine consultant will evaluate all potential plasma exchange patients. Those with prolonged PT, PTT, platelet count less than 100,000 or receiving anticoagulant therapy will undergo plasma exchange only if the consultant considers this to be safe. For prednisone: uncontrolled diabetes mellitus (requiring greater than 100 units of insulin/day with the concurrence of the Endocrinology consultant), active infection including hepatitis B or C (if that is the advice of the Hepatology consultant), infection with HIV (as these patients are at increased risk of avascular necrosis), other active infection (if that is the advice of the Infectious Disease consultant), history of avascular necrosis or bone densitometry indicating bone mass less than 2SD below normal, active ulcer disease, history of steroid-induced psychosis, morbid obesity, positive PPD or history of past positive PPD without adequate treatment are excluded. For Cyclophosphamide: A) Allergy or hypersensitivity to cyclophosphamide B) Leukocyte less than 3000 cells/microliter or ANC less than 1500 cells/microliter or evidence of bone marrow compromise C) Prior irradiation to the heart or therapy with doxorubicin or other cardiotoxic medication (may increase the risk for cardiotoxicity) D) Peritoneal dialysis, as there is no published evidence that cyclophosphamide metabolites can be safely removed. E) Certain drugs will be used with caution or avoided. Barbiturates and phenytoin induce the hepatic enzymes that metabolize cyclophosphamide and therefore if these medications are required, cyclophosphamide doses may need to be increased to achieve a comparable immunosuppressive effect. Drugs that inhibit cyclophosphamide metabolism include allopurinol, imipramine, and phenothiazines, chloramphenicol and chlorpromazine; these drugs will be avoided. NSAID increase the risk of hyponatremia; these drugs will be avoided.