• INCLUSION CRITERIA:
• Patients with podocyte diseases, MCD, FSGS (including idiopathic, secondary, and hyperfiltration variants), and CG (including HIV-associated variant), who meet the following criteria:
• An adequate renal biopsy, defined as having a minimum of 10 glomeruli for light microscopy and a minimum of 3 glomeruli for electron microscopy. Patients who have biopsies that contain fewer glomeruli will be offered the opportunity to undergo a research biopsy to determine eligibility.
• Adults greater than or equal to 16 years of age. The rationale for excluding younger children is that retinoids may carry greater toxicity in children, as there are reports of premature epiphyseal closure, development of slender long bones, and periostial thickening.
• Prior treatment with at least two immunosuppressive agents that have been shown to induce remission in MCD and FSGS: glucocorticoids, cyclosporine, tacrolimus, cyclophosphamide, chlorambucil, and mycophenolate mofetil. Therapy with each agent must last at least 8 weeks. Exemptions will be made for those with contraindications to these medications or those who cannot tolerate these medications. The rationale is to recruit patients who have failed conventional therapy. All patients will be off immunosuppression for at least 4 weeks before starting retiniods in order to avoid a confounding effect.
• Three 24h urine collections with mean protein excretion greater than or equal to 3.5 g/d obtained within one month prior to enrolling in the study. These 24hr urine collections will be collected after the patient has been on a stable dose of ACE inhibitor or ARB for at least 4 weeks (the maximal antiproteinuric effect of these medications occurs after 4 weeks). The rationale is that patients with nephrotic-range proteinuria are at high risk for progressive renal disease, justifying participation in a clinical trial with novel agents.
• Blood pressure of less than or equal to 130/80 on a stable dose of ACE inhibitor or ARB for at least 1 month or greater than or equal to 75 percent of measurements before the entry of the study. The rationale is that uncontrolled hypertension can exacerbate proteinuria.

EXCLUSION CRITERIA:

• Pregnancy, breastfeeding, or unwillingness to use at least two contraceptive methods (at least one of which must be primary, including tubal ligation, partner vasectomy, oral contraceptives, implanted contraceptives, and intrauterine device). The rationale is that retinoids are teratogenic and are excreted in breast milk.
• Abnormal liver function test, including AST, ALT, total bilirubin, or protime. The rationale is that retinoids can be hepatotoxic. The only exception will be the following: if the cause of abnormality of LFTs is felt to be due to a specific hepatotoxic drug such as a statin and the levels are less than 2 times the upper limit of the normal AND normalize upon holding the offending drug, patients may be considered for study participation after consultation with hepatology service.
• Hypertriglyceridemia greater than 500 mg/dL despite statin/fibrate therapy. The rationale is that retinoids can increase lipids, particularly triglyceride and this can lead to pancreatitis.
• Any medical conditions requiring concurrent immunosuppression, as this pilot study is designed to evaluate the effect of retinoids as a monotherapy.
• Any medical conditions requiring concurrent use of tetracycline, minocycline, or doxycycline, due to enhanced risk of increased intracranial pressure.
• Hypersensitivity to retinoids.
• Presence of any unstable cardiovascular disease, uncontrolled diabetes with hemoglobin A1c greater than 8 percent, chronic inflammatory or infectious conditions except HIV-1 infection. Retinoids have been associated with chest pain of unclear etiology, increased serum glucose, myelosuppression and increased risk of infection. The etiology of infection is not clear but may be related to myelosuppression.
• Those with HIV-1 infection must not have any evidence for opportunistic infectious complications and have CD4 count greater than or equal to 200. Both tretinoin and isotretinoin have been safely studied in HIV-infected patients for other indications.
• GFR less than 25 ml/min/1.73m(2)estimated by 5-variable MDRD equation, as the metabolities of retinoids are excreted in part in urine, and there is a concern for increased toxicity. In participants less than 18 years of age, we will use Schwartz equation.
• Untreated depression, as retinoids have been associated with depression, suicidal ideation, and aggressive behavior. If patients manifest significant depressive symptoms, they will be included in the study only if assessed and agreed by a psychiatrist (either at NIH or other) and if they have regular follow-up visits with a psychiatrist.
• Factors that increase the risk of renal biopsy. These include the following: unwillingness to accept blood transfusion, bleeding diathesis, single kidney, small kidneys (less than 9.5 cm).
• Inability or unwillingness to undergo research renal biopsy.