Baseline characteristics and evolution of Brazilian patients with atypical hemolytic uremic syndrome: first report of the Brazilian aHUS Registry

Abstract

Background Atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease. Therefore, studies involving large samples are scarce, making registries powerful tools to evaluate cases. We present herein the first analysis of the Brazilian aHUS Registry (BRaHUS). Methods Analysis of clinical, laboratory, genetic and treatment data from patients inserted in the BRaHUS, from 2017 to 2020, as an initiative of the Rare Diseases Committee of the Brazilian Society of Nephrology. Results Cohort of 75 patients (40 adults and 35 pediatric). There was a predominance of females (56%), median age at diagnosis of 20.7 years, and a positive family history in 8% of cases. Renal involvement was observed in all cases and 37% had Low C3 levels. In the <2 years of age-group, males were predominant. Children presented lower levels of hemoglobin (p = 0.01) and platelets (p = 0.003), and higher levels of LDH (p = 0.004) than adults. Genetic analysis performed in 44% of patients revealed pathogenic variants in 66.6% of them, mainly in CFH and the CFHR1-3 deletion. Plasmapheresis was performed more often in adults (p = 0.005) and 97.3% of patients were treated with eculizumab and its earlier administration was associated with dialysis-free after 3 months (p = 0.08). Conclusions The cohort of BRaHUS was predominantly composed of female young adults, with renal involvement in all cases. Pediatric patients had lower hemoglobin and platelet levels and higher LDH levels than adults, and the most common genetic variants were identified in CFH and the CFHR1-3 deletion with no preference of age, a peculiar pattern of Brazilian patients.

We still need to talk about Hemolytic Uremic Syndrome: early recognition is key!

“…Since 2015, the pathogenicity of genetic variants has been defined 16 but not the ideal number of genes in an aHUS genetics panel, which still varies among laboratories. Although it is very important to define transplant strategies 17 and decide whether or not to discontinue complement inhibitors 18 , 19 , genetics is still not the gold standard diagnostic test for aHUS since positivity is variable 20 , 21 . It is important to highlight that one should not wait for the genetic test result to start treatment of suspected aHUS cases, especially if there is severe organ injury.…”

Ainda precisamos falar sobre a Síndrome Hemolítico-Urêmica: reconhecimento precoce é fundamental!

“…Desde 2015, a patogenicidade das variantes genéticas foi definida 16 mas não o número ideal de genes em um painel genético da SHUa, o qual ainda varia entre laboratórios. Embora seja muito importante definir estratégias de transplante 17 e decidir descontinuar ou não os inibidores do complemento 18,19 , este ainda não é o teste diagnóstico padrão-ouro para SHUa, uma vez que a positividade é variável 20,21 . É importante destacar que não se deve esperar pelo resultado do teste genético para iniciar o tratamento de casos suspeitos de SHUa, especialmente se houver lesão grave de órgãos.…”