Zand Ladan, Canetta Pietro, Lafayette Richard, Aslam Nabeel, Jan Novak, Sethi Sanjeev, Fervenza Fernando C
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Division of Nephrology and Hypertension, University of Columbia Medical Center, New York, New York, USA.
Kidney Int Rep. 2019 Oct 31;5(1):58-65. doi: 10.1016/j.ekir.2019.10.007. eCollection 2020 Jan.
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.
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.
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 ( = 0.007) and significant increase in serum albumin (3.79 to 3.93, = 0.02). There was no significant change in eGFR (65.5 to 61.1 ml/min, = 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.
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.
IgA 肾病（IgAN）是最常见的肾小球肾炎，对于蛋白尿>1 g/24 小时的患者，其进展为终末期肾病的风险很高。目前尚无已知的针对 IgAN 患者的有效治疗方法。
我们对 IgAN 患者进行了一项前瞻性开放标签试验性研究，使用促肾上腺皮质激素（ACTH）（Acthar Gel，Mallinckrodt 制药公司，新泽西州贝德明斯特），剂量为每周皮下注射 80 单位，共 6 个月，并对患者进行了总共 12 个月的随访。入选患者尽管肾素-血管紧张素-醛固酮系统（RAAS）充分阻断，但尿蛋白仍>1 g/24 小时，且入组时估计肾小球滤过率（eGFR）>30 ml/min。
共招募了 19 名患者并随访 1 年。基线时，平均年龄为 34.9±10.5 岁，其中男性 11 名，女性 8 名，白种人 14 名，亚洲人 5 名。在 12 个月时，24 小时尿蛋白从 2.6 g 显著下降至 1.3 g（P = 0.007），血清白蛋白显著升高（从 3.79 升至 3.93，P = 0.02）。eGFR 无显著变化（从 65.5 降至 61.1 ml/min，P = 0.1）。完全缓解 0 例，部分缓解 8 例（42%）。共有 6 次感染：2 次为病毒感染，4 次需要抗生素治疗（2 次鼻窦炎、1 次肺炎、1 次中耳炎）。最常见的不良事件包括痤疮、潮热、酸痛和焦虑。
总之，对于 24 小时尿蛋白>1 g 且 eGFR>30 ml/min 的 IgAN 患者，在接受为期 6 个月的 ACTH 治疗后，12 个月随访时 24 小时尿蛋白显著降低，eGFR 保持稳定。
