New insights into postrenal transplant hemolytic uremic syndrome

Abstract

After renal transplantation, hemolytic uremic syndrome (HUS) may occur either as a recurrent or de novo form. Over the past decade, much effort has been devoted to elucidating the pathogenesis of atypical HUS (aHUS). Approximately 60-70% patients with aHUS have mutations in regulatory factors of the complement system or antibodies against complement factor H. The risk of post-transplant recurrence of aHUS depends on the genetic abnormality involved, and ranges from 15% to 20% in patients with mutations in the gene that encodes membrane cofactor protein and from 50% to 100% in patients with mutations in the genes that encode circulating regulators of complement. Given the poor outcomes associated with recurrence, isolated renal transplantation had been contraindicated in patients at high risk of aHUS recurrence. However, emerging therapies, including pre-emptive plasma therapy and anti-C5 component monoclonal antibody (eculizumab) treatment have provided promising results and should further limit indications for the risky procedure of combined liver-kidney transplantation. Studies from the past 2 years have demonstrated genetic abnormalities in complement regulators in 30% of renal transplant recipients who experienced de novo HUS after renal transplantation. This finding suggests that the burden of endothelial injury in a post-transplantation setting may trigger de novo HUS in the presence of mild genetic susceptibility to HUS.

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

“…These relapses may be ascribed either to endothelial microchimerism or to associated mutations of factor H or factor I [120,121] . There are few reports of renal-transplant outcomes in patients with C3 or C3B mutations; however, according to these reports, the relapse incidence appears to be high [66,122] . In addition, a high incidence of HUS recurrence has been described in patients with anti-factor H antibodies; such patients may benefit from treatment with plasma therapy and rituximab if the treatment is initiated immediately before transplantation [118,123] .…”

Current treatment of atypical hemolytic uremic syndrome

“…Eculizumab has been used pre-emptively for renal transplant in aHUS (68) and prophylactically after renal transplantation (43,54,69). The best results in terms of normalizing renal function were obtained when eculizumab was given as soon as possible after onset of aHUS (43). Eculizumab also successfully treated skin necrosis in aHUS (41).…”

“…The clinical and laboratory manifestations partly responded to treatment with daily PE and intravenous immunoglobulin but resolved rapidly and completely on eculizumab (67). Eculizumab has been used pre-emptively for renal transplant in aHUS (68) and prophylactically after renal transplantation (43,54,69). The best results in terms of normalizing renal function were obtained when eculizumab was given as soon as possible after onset of aHUS (43).…”

“…In those with a CFH mutation, 60-70% die or develop ESKD after their first presentation (39). The disease frequently recurs after renal transplantation (43).…”

“…Some patients become refractory to plasma, or have allergic reactions or have complications from the procedure. Renal transplant is associated with a very high incidence of recurrent aHUS and graft loss despite the use of plasma therapy (43).…”