IPNA clinical practice recommendations for the management of aHUS and secondary TMA in children

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement-mediated injury of the vascular endothelium. We present Clinical Practice Recommendations (CPRs) and Practice Points (CPPs) for the diagnosis and management of aHUS and the related spectrum of secondary thrombotic microangiopathies (TMAs) in children, based on current evidence and expert consensus, developed by a panel of international experts including pediatric nephrologists associated with the International Pediatric Nephrology Association (IPNA), kidney pathologists, geneticists, and adult nephrologists. The guidance focuses exclusively on pediatric populations, in alignment with IPNA's scope, and does not address diagnoses exclusive to the adult age group.

Six structured clinical questions were formulated using the PICO (Population, Intervention, Comparator, Outcomes) framework, guiding comprehensive literature reviews. Recommendations were developed through expert consensus using a modified Delphi process. Two predefined levels of agreement-agreement and strong agreement-were used, with consensus on either level requiring ≥ 80% concurrence among panel members.

A total of 51 CPRs for the diagnosis and management of genetic aHUS, autoimmune aHUS, aHUS in the setting of kidney transplantation, and secondary TMA are presented. Additionally, 9 CPPs provide guidance for the management of secondary TMA. Importantly, all guidance is contextualized to also reflect the distinct epidemiology and healthcare landscapes of less well-resourced countries.

These recommendations, based on global consensus, aim to standardize and provide guidance for the diagnostic work-up and treatment of aHUS and secondary TMAs in children worldwide, thus ultimately improving patient outcomes. In addition, this guidance supports implementation efforts in resource-limited settings and provides direction for future research.