Kidney Week

Abstract: PUB559

Scleroderma Renal Crisis – A Genetic Complementopathy?

Session Information

• Publication Only

Category: Trainee Case Reports

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Waitzman, Joshua S., Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States

Joshua S. Waitzman,

• Gunasekaran, Niranjan, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States

Niranjan Gunasekaran,

• Kanwar, Yashpal S., Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States

Yashpal S. Kanwar,

• Ghossein, Cybele, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States

Cybele Ghossein,

Introduction

Complement dysfunction is a major contributor to the pathophysiology of atypical hemolytic uremic syndrome (aHUS). Scleroderma renal crisis (SRC) shares many clinical and pathologic features with aHUS. We present a case of SRC in a patient with a homozygous mutation associated with aHUS.

Case Description

A 44-year-old woman with a 17-year history of scleroderma presented to rheumatology clinic with new onset hypertension and a rising creatinine. She was admitted to the hospital and started on captopril for blood pressure control; her blood pressure was lowered to her baseline within 48 hours. A 24-hour urine protein demonstrated 1.7 g proteinuria. Given the late presentation of her kidney injury relative to her diagnosis of scleroderma, she underwent a renal biopsy. Blood vessels showed moderate-to-severe wall thickening with semi-occlusive/occlusive changes and some of the vessels revealed “onion skinning,” consistent with SRC (Fig 1). Her creatinine stabilized at 2 mg/dl and she was discharged. She was readmitted one week later with recurrent hypertension and an elevated creatinine. The patient underwent genotyping for mutations of the complement pathway and was found to have a homozygous polymorphism within an intron of the membrane cofactor protein/CD46, which has been associated with aHUS. She was initiated on eculizumab. She subsequently developed an infection and had an antibiotic drug reaction that caused her renal disease to progress and she was initiated on dialysis.

Discussion

SRC and aHUS are two entities that are clinically and pathologically similar. SRC pathogenesis may be related to alternative complement pathway dysfunction.

Fig 1