Abstract: SA-OR062
An Open-Label Pilot Study of ACTH in the Treatment of IgA Nephropathy at High Risk of Progression
Session Information
- IgA Nephropathy and Lupus Nephritis
October 27, 2018 | Location: 6E, San Diego Convention Center
Abstract Time: 05:18 PM - 05:30 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Zand, Ladan, Mayo Clinic, Rochester, Minnesota, United States
- Canetta, Pietro A., Columbia Universtiry, New York, New York, United States
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Aslam, Nabeel, Mayo Clinic Florida, Jacksonville, Florida, United States
- Sethi, Sanjeev, Mayo Clinic, Rochester, Minnesota, United States
- Leung, Nelson, Mayo Clinic, Rochester, Minnesota, United States
- Fervenza, Fernando C., Mayo Clinic, Rochester, Minnesota, United States
Background
Patients with IgAN and elevated proteinuria despite renin-angiotensin inhibition (RASI) are at risk of progressive CKD, and therapeutic options are limited. ACTH has been shown to lower proteinuria in certain proteinuric kidney diseases. We hypothesized that it may be effective in lowering proteinuria and preserving renal function in patients with IgAN at high risk of progression.
Methods
We conducted a prospective open-label pilot study in patients with IgAN using ACTH (H.P. Acthar® Gel) at a dose of 80 units SC twice weekly for a total of 6 months (m) and followed patients for a total of 12m. Patients had to have urinary protein (UP) > 1 g/24 hr despite adequate RASI & eGFR >30 ml/min at enrollment. Secondary IgAN & those with hepatitis were excluded. Glucocorticoids could not have been used for the prior 3m. Primary endpoint was defined as achieving CR (24 hr UP <300 mg & ≤10% reduction in eGFR) or PR (≥50% reduction in UP and ≤25% reduction in eGFR).
Results
Twenty patients were enrolled. One was removed from the study at 3m as he was hepatitis B positive. Another patient withdrew at 6m due to progression of IgAN but was included in the analysis at 12m. At baseline, the mean age was 34.5 ± 10.5 yrs with 11 males & 8 females, 14 Caucasian & 5 Asians. At 12m there was a statistically significant decline in 24hr UP from 2.8 to 1.9 g (P=0.006) 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 8 PRs (42%). There were total of 4 infections (1 pneumonia, 1 otitis media, and 2 sinus infections) that required antibiotics. Most common adverse events included acne, hot flashes, and anxiety.
Conclusion
Patient with IgAN with >1 g/24 hr UP and eGFR >30ml/min had a significant reduction in 24hr UP with stable eGFR at 12m follow up after being treated with 6 months of ACTH.
Patients' clinical and renal charactersitics
| Baseline (n=19) | 12 months (n=19) | P value | |
| sBP (mmHg) | 124.2 ± 20.2 | 118.8 ± 11.1 | 0.24 |
| dBP (mmHg) | 76.0 ± 8.2 | 76.6 ± 9.8 | 1.0 |
| BMI (kg/m2) | 27.7 ± 7.4 | 28.5 ± 7.0 | 0.18 |
| Serum creatinine (mg/dL) | 1.40 ± 0.49 | 1.55 ± 0.64 | 0.1 |
| eGFR - CKD-EPI (ml/min) | 65.5 ± 28.8 | 61.1 ± 31.1 | 0.1 |
| Serum albumin (g/dL) | 3.79 ± 0.54 | 3.93 ± 0.39 | 0.02 |
| 24 hour urinary protein (mg) | 2821 ± 1234 | 1963 ± 1668 | 0.006 |
Funding
- Commercial Support – Mallinckrodt