A Dose Escalation Study of Long-acting ACTH Gel in Membranous Nephropathy

Inclusion Criteria:• Idiopathic MN with diagnostic biopsy performed less than 36 months from the time of dose randomization. * Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to ACTH treatment and have adequately controlled blood pressure (BP \<130/75 mm Hg in \>75% of the readings). Patients with documented evidence of \>3 months treatment with maximal Ang II blockade, target BP (BP \<130/75 mm Hg in \>75% of the readings) and who remain with proteinuria \>4.0g/24h may enter the ACTH phase of the study without the need to have the run-in/conservative phase of the study. * Proteinuria as measured by Uprot/Ucr \> 4.0 on a spot sample aliquot from a 24-hour urine collection. The choice of Uprot/UCr is in accord with recent NKF-CKD guidelines.\[9\] * Estimated GFR ≥ 40 ml/min/1.73m2 while taking ACEI/ARB therapy. The GFR will be estimated using the 4 variable MDRD equation as published in the NKF-CKD guidelines.\[9\] The same NKF-CKD guidelines also promote the use of estimated GFR (GFRest) values rather than serum creatinine levels or CrCl measurements as the preferred non-invasive method of determining glomerular filtration rates.\[9\] Exclusion Criteria:• Age \<18 years. * Estimated GFR \< 40 ml/min/1.73m2, or serum creatinine \>2.0 mg/dl. * Renal biopsy showing more than 30% glomerulosclerosis and/or tubular atrophy. * Patient must be off glucocorticoid, calcineurin inhibitors (cyclosporin A, tacrolimus) or mycophenolic mofetil for \> 1 month, and alkylating agents or rituximab for \>6 months. * Resistance to the following immunosuppressive routines e.g. steroids alone, calcineurin inhibitors plus or minus steroids, cytotoxic agents plus or minus steroids. * Patients with active infections or secondary causes of MN (e.g. hepatitis B, SLE, medications, malignancies). Testing for HIV, Hepatitis B and C should have occurred \< 2 years prior to enrollment into the study. * Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy. Patients who have recent history of steroid induced diabetes but no evidence on renal biopsy performed within 6 months of entry into the study are eligible for enrollment. * Pregnancy or nursing - for safety reasons. * Acute renal vein thrombosis documented prior to entry by renal US or CT scan and requiring anticoagulation therapy.