Atypical haemolytic uremic syndrome with refractory multiorgan involvement and heterozygous CFHR1/CFHR3 gene deletion

We present this challenging case report of Atypical Haemolytic Uremic Syndrome (aHUS) presenting with multi-organ involvement in a patient and heterozygous CFHR1/CFHR3 gene variant, which was refractory to initial eculizumab therapy.

A forty-three year old female presented with aHUS and had heterozygous disease-associated deletions in the complement genes CFHR1/CFHR3. She had progressive kidney failure and severe extra-renal manifestations including cardiomyopathy and haemorrhagic cystitis; as well as pulmonary, gastrointestinal and neurological involvement. The initial kidney biopsy revealed thrombotic microangiopathy (TMA) changes involving all glomeruli. Clinical improvement was initially seen during eculizumab initiation with suppressed CH50 level, but a new rhinovirus/enterovirus upper respiratory tract infection triggered further severe multi-organ disease activity. The extra-renal manifestations stabilised, then ultimately improved after a period of eculizumab dose intensification. However, the impact on dose intensification on this improvement is unclear. Despite the extra-renal clinical improvement, she ultimately progressed to end-stage kidney disease (ESKD), commencing peritoneal dialysis for three years before undergoing a successful uncomplicated cadaveric kidney transplant without prophylactic eculizumab. Two years after transplant, she has excellent transplant graft function without any further disease recurrence.

This case highlights the concept of extra-renal manifestations in aHUS initially resistant to eculizumab, which potentially responded to dose intensification. Whilst organ injuries are potentially reversible with timely targeted treatment, it appears that the kidneys are most vulnerable to injury.