Kidney Week

Abstract: FR-PO0430

Complement-Mediated Thrombotic Microangiopathy Unmasked by an Autoimmune Overlap Syndrome: A Diagnostic Challenge

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

• Mathews, Hella Fiona, Northwell Health, New Hyde Park, New York, United States

Hella Fiona Mathews, MD

• Wanchoo, Rimda, Northwell Health, New Hyde Park, New York, United States

Rimda Wanchoo, MD

• Jhaveri, Kenar D., Northwell Health, New Hyde Park, New York, United States

Kenar D. Jhaveri, MD, FASN

• Kim, Sungsoo, Northwell Health, New Hyde Park, New York, United States

Sungsoo Kim, MD

Introduction

Thrombotic microangiopathy (TMA) is a life-threatening condition characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and organ damage. It’s critical to distinguish between etiologies--including aHUS, scleroderma renal crisis (SRC), and antiphospholipid syndrome (APLS), as management is significantly different. This is a complex case of complement-mediated TMA in a patient with an autoimmune overlap syndrome.

Case Description

A 55-year-old female with HTN and kidney stones presented with a SBP >200 mmHg and AMS. Labs showed AKI (baseline Scr 0.88mg/dL),presenting Scr 2.59 mg/dL and progressively worsening, elevated LDH, low haptoglobin, acute anemia with schistocytes on peripheral blood smear and thrombocytopenia consistent with TMA. UA showed microscopic hematuria and proteinuria (UPCR 0.7). PLEX and steroids were initiated on admission as suspicion for TTP was high. PLEX was discontinued after three sessions when ADAMTS13 resulted at 64% excluding TTP. Serologies revealed ANA 1:320, positive anti-RNP (2.1AI), low C4 (10 mg/dl), and normal C3. Other serologues were negative.Echo showed LVH. Secondary HTN workup revealed elevated aldo(41 ng/dl) and PRA (11 ng/ml/hr) but negative RA duplex. Genetic testing identified a homozygous CFHR1-CFHR3 deletion. Renal biopsy confirmed TMA with severe arteriosclerosis, mild IFTA, and no immune complex deposition. She also had features of APLS/MCTD/scleroderma given sclerodactyly, anti-RNP positivity, and six prior miscarriages. She was started on eculizumab weekly for aHUS, captopril for scleroderma renal crisis and mycophenolate mofetil, apixaban for APLS. Pt is currently dialysis dependent and is monitored for renal recovery.

Discussion

This case highlights the diagnostic complexity of TMA when multiple conditions coexist- aHUS and autoimmune disease. The homozygous CFHR1-CFHR3 deletion provided genetic evidence of complement dysregulation, while the autoimmune phenotype — including sclerodactyly, anti-RNP positivity, recurrent miscarriages, and severe hypertension—suggested SRC and APLS/MCTD as potential complement-activating triggers. A "two-hit" model likely applies here; wherein genetic complement susceptibility was unmasked by autoimmune activation. This case highlights the need for comprehensive genetic, serological, and histopathological evaluation in TMA to guide targeted, multidisciplinary therapy.