An Open-Label Pilot Study of Adrenocorticotrophic Hormone in the Treatment of IgA Nephropathy at High Risk of Progression

Ladan Zand, Pietro Canetta, Richard Lafayette, Nabeel Aslam, Novak Jan, Sanjeev Sethi, Fernando C Fervenza, Ladan Zand, Pietro Canetta, Richard Lafayette, Nabeel Aslam, Novak Jan, Sanjeev Sethi, Fernando C Fervenza

Abstract

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis with high risk of progression to end-stage renal disease in patients with proteinuria >1 g/24 hours. There are no known effective treatments in patients with IgAN.

Methods: We conducted a prospective open-label pilot study in patients with IgAN using adrenocorticotrophic hormone (ACTH) (Acthar Gel, Mallinckrodt Pharmaceuticals, Bedminster, NJ) at a dosage of 80 units subcutaneously twice weekly for a total of 6 months and followed patients for a total of 12 months. Patients had to have urinary protein >1 g/24 hours despite adequate renin-angiotensin-aldosterone system (RAAS) blockade and estimated glomerular filtration rate (eGFR) >30 ml/min at enrollment.

Results: A total of 19 patients were recruited and followed for 1 year. At baseline, the mean age was 34.9 ± 10.5 years with 11 men and 8 women, and 14 Caucasian and 5 Asian individuals. At 12 months, there was a statistically significant decline in 24-hour urinary protein from 2.6 to 1.3 g (P = 0.007) and significant increase in serum albumin (3.79 to 3.93, P = 0.02). There was no significant change in eGFR (65.5 to 61.1 ml/min, P = 0.1). There were 0 complete remissions and 8 partial remissions (42%). There were a total of 6 infections: 2 were viral and 4 required antibiotic therapy (2 sinusitis, 1 pneumonia, 1 otitis media). The most common adverse events included acne, hot flashes, soreness, and anxiety.

Conclusion: In summary, patients with IgAN with >1 g/24-hour urinary protein and eGFR >30 ml/min had a significant reduction in 24-hour urinary protein with stable eGFR at 12-month follow-up after being treated with 6 months of ACTH.

Keywords: ACTH; IgA nephropathy; proteinuria.

© 2019 International Society of Nephrology. Published by Elsevier Inc.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Proteinuria at baseline and 6-month and 12-month follow-up.

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