Renal recovery with eculizumab in atypical hemolytic uremic syndrome following prolonged dialysis

Abstract

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) which encompasses hemolytic anemia, thrombocytopenia, and organ impairment. Around 10% of cases are atypical HUS (aHUS), a rare disease with poor outcomes caused by uncontrolled activation of the alternative complement pathway. This case describes a young woman with clinical manifestations compatible with TMA during childhood and adolescence who was formally diagnosed with aHUS at the age of 21. She was managed with intensive plasma exchange and hemodialysis, which failed to improve her severe acute kidney injury and other hematological manifestations of aHUS. This was further compounded by several episodes of flash pulmonary edema and the posterior reversible encephalopathy syndrome (PRES). Treatment with the monoclonal anti-C5 inhibitor, eculizumab, improved all hematological parameters with almost full renal recovery following 3.5 months of dialysis. So far, long-term use of eculizumab (> 11 months) continues to be effective and without complication. Our case illustrates the difficulty but importance of early consideration of aHUS in patients presenting with TMA. More importantly, we highlight that near-normal renal recovery may be attained with eculizumab in adults even after a long dependence on dialysis - an observation that has not been reported in the literature so far.

Efficacy and safety of eculizumab in childhood atypical hemolytic uremic syndrome in Japan

“…suggested that earlier initiation of eculizumab therapy was associated with better improvement of renal function [9][10][11], although some cases experienced a significant improvement in renal function after RRT of several months [9,24,25]. In our study, two of the eight patients who required RRT during the course of the disease (Patients 1, 3) started eculizumab more than one month after the onset of aHUS.…”

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

“…We are aware of two patients who started eculizumab after 90 and 225 days on dialysis and did not recover renal function [55,131], but also of two patients who recovered normal [132] or nearly normal [133] serum creatinine levels despite eculizumab initiation after 4 and 3.5 months on dialysis, respectively. Therefore eculizumab treatment is reasonable to consider for patients requiring dialysis for 3-4 months or even more and should be maintained for at least 3-6 months before concluding there has been no benefit.…”

Severe Case of Thrombotic Microangiopathy with a Delayed Diagnosis of Atypical Haemolytic Uraemic Syndrome Successfully Managed with Eculizumab

“…On discharge, the patient had stage 4 chronic kidney disease; at follow-up, levels of creatinine remained near normal, eGFR had increased to 35 ml /min/1.73 m 2 , and a renal biopsy found no signs of TMA. A similarly impressive degree of renal recovery has also been reported recently in a case of eculizumab therapy after >3 months of dialysis [5] , but is not seen in all cases if treatment with eculizumab is initiated too late [6] . Our case indicates that eculizumab therapy is of clinical benefit despite delayed diagnosis of aHUS and established kidney failure, an outcome also reported by Povey et al [5] .…”

“…A similarly impressive degree of renal recovery has also been reported recently in a case of eculizumab therapy after >3 months of dialysis [5] , but is not seen in all cases if treatment with eculizumab is initiated too late [6] . Our case indicates that eculizumab therapy is of clinical benefit despite delayed diagnosis of aHUS and established kidney failure, an outcome also reported by Povey et al [5] . The long-term effects of eculizumab treatment are still being established.…”