We report the first cases of atypical hemolytic and uremic syndrome associated with
complement factor H (
CFH) deficiency in native kidneys and
glomerulonephritis with isolated C3 deposits after
kidney transplantation. Two boys developed atypical hemolytic and uremic syndrome at 16 and 11 months of age, associated with low C3 and CFH levels. Both rapidly progressed to
end-stage renal failure and received a kidney transplant. Patient 1 had combined CFH and
complement factor I (
CFI) heterozygous mutations and a
membrane cofactor protein (gene symbol, CD46) gene polymorphism. Five years posttransplantation, an allograft biopsy specimen showed numerous mesangial and extramembranous C3 deposits, although the patient had no biological sign of glomerulopathy. Nine years after
transplantation, he was well with stable kidney function. Patient 2, who had a homozygous CFH mutation, developed
glomerulonephritis with isolated C3 deposits 5 months after
kidney transplantation while he was treated for early recurrence of
hemolytic anemia. Four years later, the second kidney transplant biopsy specimen showed recurrence of
thrombotic microangiopathy. Six years posttransplantation, kidney function was stable and complete blood cell count was normal with regular plasma
therapy. These observations suggest that constitutional dysregulation of the alternative pathway is associated with a wide spectrum of
kidney diseases, and
glomerulonephritis with isolated C3 deposits and
thrombotic microangiopathy may be different expressions of the same condition. Several factors could influence the disease, such as degree of CFH haploinsufficiency and other
complement alternative pathway regulator abnormalities, such as a
membrane cofactor protein polymorphism.