Eculizumab Use in Scleroderma Renal Crisis With Thrombotic Microangiopathy: A Case Report

Abstract

A Black woman in her 40s with past medical history significant for obesity treated with Roux-en-Y bypass surgery and a history of Raynaud's phenomenon, presented with acute pulmonary edema secondary to severe malignant hypertension and critically accelerated acute kidney injury, with evidence of systemic microangiopathic hemolytic anemia in the setting of clinical suspicion of systemic sclerosis sine scleroderma. Renin-angiotensin system blockade (angiotensin-converting enzyme inhibitor) was immediately started at the maximum possible dose in the setting of scleroderma renal crisis. Despite better control of blood pressure and volume status, kidney function continued to rapidly decline, thus a decision was made to go ahead with a kidney biopsy on day 3 of admission, which revealed severe features of scleroderma renal crisis with active thrombotic microangiopathy. The multidisciplinary team elected to treat the patient with terminal complement blockade using eculizumab in addition to high dose lisinopril and blood pressure control. Her serum creatinine peaked at 9.3 mg/dL shortly after eculizumab initiation, but improved soon after, dropping to 2.8 mg/dL after completion of the final eculizumab dose and 1.8 mg/dL 3 years later.

Keywords: Scleroderma renal crisis; acute kidney injury; case report; complement blockade; thrombotic microangiopathy.

Figure 1

Kidney biopsy showing acute thrombotic microangiopathy associated with severe arteriolar narrowing. (A) Low magnification, periodic acid–Schiff stain showing moderate chronic tubular atrophy and minimal acute tubular injury. (B) Arteriole (black arrow) with typical onion-skin muco-intimal thickening and sclerosis with widespread glomerular hypoperfusion. (C, D) Higher magnification showing acute thrombotic microangiopathy involving glomerular capillaries and arteriole (black arrow). (E) Fibrinogen immunostaining. (F) C4d immunostaining in arteriole (white arrow) and glomerular capillaries but not in peritubular capillaries.

Figure 2

Creatinine over time since hospital admission. Patient presented to the emergency department with a creatinine of 4.5 mg/dL from a baseline at 0.8 mg/dL 4 years prior. Kidney function rapidly deteriorated and the patient was rapidly started on angiotensin conversion enzyme inhibitors followed by complement blockade, and subsequently showed sustained recovery with a creatinine of 1.8 mg/dL more than 3 years after eculizumab discontinuation. Angiotensin-converting enzyme inhibitor (ACEi) treatment has been maintained.