title: Advanced diabetic nephropathy with nephrotic range proteinuria: a pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1.
abstract: OBJECTIVE
  Adrenocorticotropic hormone (ACTH) is able to reduce proteinuria in nondiabetic glomerulopathies through activation of melanocortin receptors (MCR) expressed in the podocyte. To determine the efficacy of ACTH, we conducted a randomized, open-label pilot trial of ACTH gel in patients with advanced diabetic nephropathy.
  
  
  METHODS
  Twenty-three (23) patients with diabetic nephropathy were randomized to daily subcutaneous (SQ) injections of 16 or 32 units of ACTH gel for six months. Outcome. The primary endpoint was the percentage of patients achieving a complete remission (<300 mg/24 hours) within 6 months. Exploratory endpoints included the percentage of partial (50% reduction) remissions, changes in Cr, and urinary cytokine markers.
  
  
  RESULTS
  After 6 months of ACTH gel therapy, 8 of 14 (57%) patients achieved a complete (n = 1) or partial (n = 7) remission. In the low-dose ACTH gel group (16 units), urinary protein fell from 6709 + 953 to 2224 + 489 mg/24 hrs (P < 0.001). In contrast, 2 of 6 patients in the 32-unit group achieved partial remission, but aggregate proteinuria (5324 + 751 to 5154 + 853 mg/24 hours) did not change. Urinary VEGF increased from 388 to 1346 pg/mg urinary creatinine (P < 0.02) in the low-dose group but remained unchanged in the high-dose group.
  
  
  CONCLUSIONS
  ACTH gel stabilizes renal function and reduces urinary protein for up to 6 months after treatment. The ClinTrials.gov identifier is NCT01028287.
authors.affiliation: Internal Medicine/Nephrology, University of Tennessee College Medicine, Chattanooga, TN 37403, USA ; Southeast Renal Research Institute, 45 East Main Street, Chattanooga, TN 37408, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Tumlin
authors.forename: C M
authors.initials: CM
authors.lastname: Galphin
authors.forename: B H
authors.initials: BH
authors.lastname: Rovin
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage* / Q000009:adverse effects; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000652:urine; D018450:Disease Progression; D005260:Female; D005782:Gels; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy* / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000652:urine*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005782:Gels; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000324:Adrenocorticotropic Hormone