Kidney Week

Abstract: SA-PO0687

Complement-Mediated Thrombotic Microangiopathy in Scleroderma Renal Crisis with CFH-H3 Risk Haplotype and Response to C5 Blockade

Session Information

• Glomerular Diseases: Complement-Mediated Glomerulopathies and Infection-Related GN
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Chung, Tung-Ling, Kaohsiung Veterans General Hospital, Kaohsiung, Kaohsiung City, Taiwan

Tung-Ling Chung, MD

• Lee, Po-Tsang, Kaohsiung Veterans General Hospital, Kaohsiung, Kaohsiung City, Taiwan

Po-Tsang Lee, MD

• Hsu, Chih-yang, Kaohsiung Veterans General Hospital, Kaohsiung, Kaohsiung City, Taiwan

Chih-yang Hsu, MD

• Huang, Chien-Wei, Kaohsiung Veterans General Hospital, Kaohsiung, Kaohsiung City, Taiwan

Chien-Wei Huang

• Chen, Xin-You, Kaohsiung Veterans General Hospital, Kaohsiung, Kaohsiung City, Taiwan

Xin-You Chen

• Chuang, Hao-Wen, Kaohsiung Veterans General Hospital, Kaohsiung, Kaohsiung City, Taiwan

Hao-Wen Chuang

• Chen, Chien-Liang, Kaohsiung Veterans General Hospital, Kaohsiung, Kaohsiung City, Taiwan

Chien-Liang Chen

Introduction

Scleroderma renal crisis (SRC) is a life-threatening complication characterized by accelerated hypertension, acute kidney failure (AKI) and thrombotic microangiopathy (TMA). Endothelial injury is thought to play a central role in the pathogenesis of SRC-associated TMA, while emerging evidence suggests that complement activation may also contribute. Although angiotensin-converting enzyme inhibitors (ACEi) remain the standard treatment, complement C5 blockade may provide therapeutic benefit.

Case Description

A 70-year-old male with hypertension and diabetes presented with progressive dyspnea for 2 weeks. Laboratory evaluation revealed AKI (Cr 3.42 mg/dL; baseline 1.15 mg/dL), MAHA (hb 4.7 g/dL, LDH 633 U/L, schistocytes), and thrombocytopenia (84k/μL). Normal ADAMTS-13 activity excluded thrombotic thrombocytopenic purpura. Serologic testing revealed high ANA (1:2560), low C3 (78.2 mg/dL) and C4 (9.5 mg/dL), and elevated anti-Scl-70 Ab (>240 U/mL). Physical examination was notable for sclerodactyly and “salt-and-pepper” skin changes over the neck. Systemic sclerosis with SRC was diagnosed and ACEi treatment was initiated. Kidney biopsy findings were compatible with TMA. However, persistent MAHA and renal deterioration requiring hemodialysis raised suspicion for complement-mediated TMA (C-TMA) overlapping with SRC. After multidisciplinary discussion, eculizumab was initiated, resulting in significant improvement in MAHA. Genetic testing reveals the core coding variants of CFH-H3 risk haplotype (Val62Ile, His402Tyr, and Glu936Asp). After 2 months of treatment, MAHA was sustained in remission, although the patient remained dialysis-dependent.

Discussion

This case suggests a potential role of complement dysregulation in SRC-associated TMA. Despite ACEi therapy, the patient’s hemolysis improved only after initiation of eculizumab. The CFH-H3 risk haplotype is associated with reduced factor H levels and may create a “second-hit” susceptibility to complement overactivation during vascular stress. Early recognition of C-TMA in SRC patients and prompt initiation of C5 blockade may improve hematologic outcomes.

Hemolytic parameters improved after initiation of eculizumab.