Low factor H-related 5 levels contribute to infection-triggered haemolytic uraemic syndrome and membranoproliferative glomerulonephritis

Dysregulation of the alternative complement pathway is a major pathogenic mechanism in two rare renal diseases: atypical haemolytic uraemic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN). We report on a 66-year-old male with chronic hepatitis C virus (HCV) infection and a combined liver-kidney transplant that was diagnosed with MPGN at the age of 63 years and a 5-year-old boy who presented with aHUS at the age of 21months following a Streptococcus pneumoniae infection. Both patients carried similar frameshift variants in the complement CFHR5 gene that segregate with reduced levels of factor H-related 5 (FHR-5). We conclude that low FHR-5 levels may predispose to viral and bacterial infections that then trigger different renal phenotypes.

Automated summary

Dysregulation of the alternative complement pathway plays a major role in the pathogenesis of atypical haemolytic uraemic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN). Both a 66-year-old male with chronic hepatitis C virus infection and a 5-year-old boy with aHUS carried similar frameshift variants in the complement CFHR5 gene, resulting in reduced levels of factor H-related 5 (FHR-5). Lower FHR-5 levels may predispose individuals to viral and bacterial infections that trigger different renal phenotypes.