Eculizumab safely reverses neurologic impairment and eliminates need for dialysis in severe atypical hemolytic uremic syndrome

Abstract

This case report describes how eculizumab reversed neurologic impairment and improved renal damage in severe atypical hemolytic uremic syndrome. A 50-year-old female, after presenting with diarrhea and abdominal pain, developed pancolitis, acute renal failure, and thrombocytopenia. The patient underwent total abdominal colectomy. Pathology confirmed ischemic colitis with scattered mesenteric microthrombi. Due to mental and respiratory decline, she remained intubated. Continuous venovenous hemodialysis was initiated. Renal failure, neurologic changes, hemolysis, thrombotic microangiopathy, and low complement levels all suggested atypical hemolytic uremic syndrome. Eculizumab 900 mg was administered intravenously on hospital day 6 and continued weekly for four doses followed by maintenance therapy. She recovered neurologically and renally after the third dose, and hematologically by the sixth dose. Her recovery has been sustained on long-term eculizumab treatment. In severe atypical hemolytic uremic syndrome, eculizumab safely reverses neurologic impairment and eliminates the need for dialysis. The optimal duration of treatment with eculizumab remains to be determined.

Keywords: atypical hemolytic uremic syndrome; eculizumab; thrombotic microangiopathy.

Figure 1

Lactate dehydrogenase (normal 108–202 U/L) shown as a function of time (hospital days). Lactate dehydrogenase gradually dropped after initiating treatment with eculizumab. Eculizumab administration is denoted by vertical tick marks (hospital days 6, 13, 20, 27, 34, 48, and day 63). Four days after the first dose, lactate dehydrogenase dropped to 837 U/L. After the second dose of eculizumab on day 13, lactate dehydrogenase dropped to 556 U/L. A week after the third dose, lactate dehydrogenase was down to 349 U/L. Three days after the sixth dose, lactate dehydrogenase was normal. It did rise slightly before the seventh dose was due.

Figure 2

C3 (normal 83–184 mg/dL) shown as a function of time (hospital days). Eculizumab administration is denoted by vertical tick marks (hospital days 6, 13, 20, 27, 34, 48, and day 63). After the second dose of eculizumab on day 13, C3 rose to 81. Thirteen days after the sixth dose, C3 was normal and remained normal.

Figure 3

Creatinine (normal 0.5–1.3 mg/dL) shown as a function of time (hospital days). Eculizumab administration is denoted with vertical tick marks (hospital days 6, 13, 20, 27, 34, 48, and day 63). The start and end dates of continuous venovenous hemodialysis are marked on the time axis by 2 carat (^) symbols (hospital days 4 and 27). Three days after the second dose of eculizumab, dialysis frequency was reduced to three times per week. Continuous venovenous hemodialysis was completely discontinued after the fourth dose of eculizumab. Despite a delayed and reduced dose of eculizumab at the seventh administration, creatinine continued to decrease to as low as 2.24 mg/dL.

Figure 4

Haptoglobin shown as a function of time (hospital days). Eculizumab administration is denoted by vertical tick marks (hospital days 6, 13, 20, 27, 34, 48, and days 63 and 69). Initial haptoglobin was <6 (normal range 62–197) mg/dL. Five days after the third dose, haptoglobin was normal and remained normal until the time the seventh dose was due. Haptoglobin then dropped precipitously, indicating an ongoing need for the drug. Haptoglobin did increase again after the seventh dose on day 63, and later normalized to 71 mg/dL three days after receiving the eighth dose on day 69.

Figure 5

C4 (normal 17–59 mg/dL) shown as a function of time (hospital days). Eculizumab administration is denoted by vertical tick marks (hospital days 6, 13, 20, 27, 34, 48, and day 63). The day after the second dose of eculizumab on day 13, C4 rose to 16. Three days after the sixth dose, C4 was normal and remained normal.

Figure 6

Magnetic resonance imaging scan findings.