Is Plasma Exchange Efficacious in Shiga Toxin‐Associated Hemolytic Uremic Syndrome? A Narrative Review of Current Evidence

Abstract

Shiga toxin‐associated hemolytic uremic syndrome (STEC‐HUS) is associated with significant mortality and morbidity. Case fatalities are often associated with severe neurological involvement in children and advanced age in adults but specific treatment is currently unavailable. Plasma exchange (PE) could theoretically enable removal of Shiga toxins, pro‐inflammatory cytokines, and prothrombotic factors and has been used in deteriorating patients with STEC‐HUS but the efficacy remains uncertain. In order to assess efficacy of PE in STEC‐HUS, a literature review was performed. PubMed, Web of Science, Embase, and LiLACS were searched for reports describing the outcomes of patients with STEC‐HUS treated with PE and 16 reports were included. Reports ranged from case reports to cohort studies and one case–control study with the largest study population coming from the 2011 German STEC‐HUS outbreak. Outcomes were variable but seemed to point towards lower case fatality rates in the elderly and improved outcomes in children with STEC‐HUS, treated with PE early in the course. However studies were mostly of low quality with risk of observation bias and confounding. Currently no definitive answers concerning the efficacy of PE in STEC‐HUS can be given, highlighting the need for well performed randomized controlled trials.

Neurological involvement in children with hemolytic uremic syndrome

“…Evidence supporting the use of supplemental treatments, such as PE or eculizumab, in STEC-HUS is lacking [48][49][50][51]. Extensive cases series and small cohort studies have been published but no randomized control trials have been reported (Supplementary Table 2) [13,15,29,33,34,[37][38][39][40][41][42][43][52][53][54].…”

Shiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, France, 2009–2017

“…Because the effectiveness of specific treatments remains unclear, BSC is the cornerstone of STEC-associated HUS treatment (2,35,36). Univariate analysis indicated that TPE was not associated with overall survival improvement, although other studies have concluded differently (37)(38)(39). However, considering the substantial overlap between the signs and symptoms of STEC-associated HUS in adults and TMA of other etiologies, some researchers believe that plasma therapy should be given until TTP or atypical HUS are ruled out (13,40).…”

Neurological Involvement in Children with Hemolytic Uremic Syndrome

“…Evidence supporting the use of supplemental treatments, such as PE or Eculizumab, in STEC-HUS is lacking. [47][48][49][50] Extensive cases series and small cohort studies have been published but no randomized control trials have been reported (Supplementary Table 2). [13,15,29,33,34,[37][38][39][40][41][42][43][51][52][53] Many specialists, whilst cautiously skeptical of the role of such treatments, tend to use supplemental therapies in severe cases of HUS, particularly in the context of CNS involvement.…”

“…[13,15,29,33,34,[37][38][39][40][41][42][43][51][52][53] Many specialists, whilst cautiously skeptical of the role of such treatments, tend to use supplemental therapies in severe cases of HUS, particularly in the context of CNS involvement. [47][48][49][50] In our cohort, we reserved additional treatments for children with severe disease, treating 20/202 children (9.9%) with PE, 4/202 (1.9%) with Eculizumab and 4/202 (1.9%) with both. Our initial approach is treatment with PE; reserving Eculizumab for use when prompt initiation of PE is not practicable or if overwhelming multi-system involvement.…”