Efficacy of Acthar gel and Tacrolimus in DNA-JB9 Positive Fibrillary Glomerulopathy

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports Pub Date : 2025-09-01 DOI:10.1016/j.ekir.2025.06.042

James A. Tumlin , Amber Podoll , Nelson Kopyt , Brad Rovin , Richard Lafayette , Andrew Bomback , Richard Glassock , Jeremy Whitson , Adam Press , Gerald B. Appel

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Abstract

Introduction

Fibrillary glomerulopathy (FGN) is a rare glomerular disease characterized by the deposition of randomly arranged fibrils that results in proteinuria and end-stage renal disease (ESRD) in up to 50% of patients within 2 years. The FACT trial is a prospective, randomized, open-labeled study of patients with biopsy-proven, DNA-JB9 positive FGN comparing the safety and efficacy of repository corticotropin (ACTH) injection, Acthar gel alone or in combination with tacrolimus on proteinuria and change in estimated glomerular filtration rate (eGFR).

Methods

Patients (N = 34) were randomized to ACTH 80 units subcutaneous 2×/wk alone or in combination with tacrolimus (1.0 mg 2×/d) for 12 months. Changes in the mean urinary protein-to-creatinine ratio (UPCR) and eGFR were reported at 6 and 12 months and last follow-up.

Results

A total of 34 patients completing 1 year of therapy were analyzed. In the ACTH-alone group (19 patients), UPCR decreased from a mean of 6.21 ± 0.8 g/g at baseline to 2.92 ± 0.90 g/g (P < 0.009) at 6 months and 1.76 ± 1.3 g/g (P < 0.02) at month 12. In the combination group (15 patients), mean UPCR decreased significantly from 6.00 ± 1.4 g/g at baseline to 4.27 ± 1.1 g/g (P < 0.01) and to 1.83 ± 0.90 g/g (P < 0.0006) at 6 and 12 months, respectively. At 12 months, combination therapy induced complete or partial responses in 13.3% and 53.3% compared with 15.8% and 26.3% in the ACTH alone group, respectively.

Conclusion

Repository ACTH (Acthar gel) significantly reduced UPCR at 6 and 12 months. The addition of tacrolimus was not additive with ACTH in reducing proteinuria or stabilization of eGFR. Acthar gel is an effective antiproteinuric therapy for DNA-JB9 positive FGN.

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阿克他凝胶联合他克莫司治疗DNA-JB9阳性原纤维性肾小球的疗效观察

原纤维性肾小球病（FGN）是一种罕见的肾小球疾病，其特征是随机排列的原纤维沉积，可在2年内导致高达50%的患者蛋白尿和终末期肾病（ESRD）。FACT试验是一项前瞻性、随机、开放标记的研究，研究对象是活检证实的DNA-JB9阳性FGN患者，比较库促肾上腺皮质激素（ACTH）注射液、Acthar凝胶单独或联合他克莫司对蛋白尿和肾小球滤过率（eGFR）变化的安全性和有效性。方法34例患者随机接受ACTH 80单位皮下单药2×/周或联合他克莫司（1.0 mg 2×/d）治疗12个月。在6个月和12个月以及最后一次随访时报告尿蛋白与肌酐比值（UPCR）和eGFR的平均变化。结果共分析了34例完成1年治疗的患者。在单独acth组（19例患者）中，UPCR从基线时的平均6.21±0.8 g/g下降到6个月时的2.92±0.90 g/g （P < 0.009）和12个月时的1.76±1.3 g/g （P < 0.02）。在联合治疗组（15例），平均UPCR在6个月和12个月时分别从基线时的6.00±1.4 g/g显著下降到4.27±1.1 g/g （P < 0.01）和1.83±0.90 g/g （P < 0.0006）。在12个月时，联合治疗引起完全或部分缓解的比例分别为13.3%和53.3%，而单独ACTH组分别为15.8%和26.3%。结论ACTH （Acthar凝胶）可显著降低6个月和12个月的UPCR。他克莫司的加入与ACTH在降低蛋白尿或稳定eGFR方面没有加法作用。Acthar凝胶是一种有效的抗蛋白尿治疗DNA-JB9阳性FGN。

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来源期刊

Kidney International Reports Medicine-Nephrology

CiteScore

7.70

自引率

3.30%

发文量

1578

审稿时长

8 weeks

期刊介绍： Kidney International Reports, an official journal of the International Society of Nephrology, is a peer-reviewed, open access journal devoted to the publication of leading research and developments related to kidney disease. With the primary aim of contributing to improved care of patients with kidney disease, the journal will publish original clinical and select translational articles and educational content related to the pathogenesis, evaluation and management of acute and chronic kidney disease, end stage renal disease (including transplantation), acid-base, fluid and electrolyte disturbances and hypertension. Of particular interest are submissions related to clinical trials, epidemiology, systematic reviews (including meta-analyses) and outcomes research. The journal will also provide a platform for wider dissemination of national and regional guidelines as well as consensus meeting reports.