Kidney Week

Abstract: FR-PO0434

Scleroderma Renal Crisis-Thrombotic Microangiopathy with Pathogenic CFH Variant and Response to Anti-C5 Therapy

Session Information

• AKI: Case Reports - TMA, Vasculitis, Immune-Mediated Injury, and Systemic Disease
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Lopez Madrid, Rosario Michelle, Johns Hopkins University, Baltimore, Maryland, United States

Rosario Michelle Lopez Madrid, MD

• Al Suradi, Haya H., Johns Hopkins University, Baltimore, Maryland, United States

Haya H. Al Suradi, MD

• Singh, Aditi, Johns Hopkins University, Baltimore, Maryland, United States

Aditi Singh, MBBS

• Wilkins, Reid C., Johns Hopkins University, Baltimore, Maryland, United States

Reid C. Wilkins, MD

• Sperati, John, Johns Hopkins University, Baltimore, Maryland, United States

John Sperati, MD, FASN

• Gautam, Samir, Johns Hopkins University, Baltimore, Maryland, United States

Samir Gautam

Introduction

Scleroderma renal crisis (SRC) is a rare life-threatening complication of systemic sclerosis seen in 1.1% with limited cutaneous variant (lcSSc). Complement activation in part mediates endothelial injury in SRC, although the prevalence of rare germline variants in complement genes is not increased in SRC. We present a case of lcSSC with RNA polymerase III positive SRC- thrombotic microangiopathy (TMA) and heterozygous pathogenic CFH variant who exhibited prompt clinical response to anti-C5 therapy.

Case Description

A 50-year-old female with invasive ductal carcinoma of the breast in remission was evaluated for acute kidney injury, anemia, thrombocytopenia, and new onset hypertension (145/90 mmHg). Labs (Table 1) raised concerns for complement mediated TMA. Eculizumab was initiated with prompt hematological response. Kidney biopsy showed endothelial swelling, focal arteriolar thrombi, severe interstitial fibrosis/tubular atrophy, and ischemic glomeruli (Fig 1). Exam showed abnormal nailfold capillaries, perioral skin tightening and positive anti-RNA polymerase III antibodies (>80 units). Diagnosis of lcSSc with SRC was made. Genetic testing revealed a heterozygous pathogenic variant in CFH gene c.3007G>T (p.Glu1003Ter). Following five weekly eculizumab doses and maximum-tolerated lisinopril, serum creatinine improved 1.17 mg/dL by week 24.

Discussion

This case illustrates that pathogenic germline complement variants may influence therapeutic decision-making in SRC, highlighting the need for further investigation into the role of adjunctive C5 inhibition in this population.