title: Atypical haemolytic uraemic syndrome with underlying glomerulopathies. A case series and a review of the literature.
abstract: BACKGROUND
  Primary or secondary glomerulonephritis has been anecdotally reported in association with atypical haemolytic uraemic syndrome (aHUS). We here report a series of six patients who developed aHUS and glomerulopathy, and review the literature on aHUS and glomerulonephritis.
  
  
  METHODS
  Out of all patients diagnosed at our unit with biopsy-proven glomerular diseases between March 2007 and October 2011, selected cases developing aHUS during the follow-up are presented. The following tests were performed in all six patients: serum C3 and C4 levels, ADAMTS13 activity, CFH levels and anti-CFH autoantibodies and genetic screening for CFH, MCP, CFI, C3 and CFHR1-3 mutations and risk haplotypes associated with aHUS.
  
  
  RESULTS
  Two hundred and forty-eight patients received a biopsy-proven diagnosis of glomerulopathy and were followed for a median of 31 months (range 2-58). Of these, six developed aHUS, within a median of 15 months (range 1-36) of their initial diagnosis of glomerulopathy. One of these patients had focal segmental glomerulosclerosis (FSGS), two membranoproliferative glomerulonephritis (MPGN) type I, one C3 glomerulonephritis and two systemic small vessel vasculitis [one granulomatosis with polyangiitis (Wegener's), one Henoch-Schoenlein purpura]. Five patients (one of them heterozygous for a CFH mutation) carried, in homo- or heterozygosity, the risk haplotype CFH-H3 (CFH tgtgt), previously described to be associated with aHUS, while another one patient was homozygous for the MCPggaac risk haplotype predisposing to aHUS when present on both alleles.
  
  
  CONCLUSIONS
  Different types of glomerulopathies can be complicated by aHUS. Several mechanisms can contribute to this association, such as nephrotic-range proteinuria, mutations or aHUS-risk haplotypes involving genes encoding alternative complement regulatory proteins in some patients and inflammatory triggers associated with systemic immune-mediated diseases.
authors.affiliation: Nephrology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Manenti
authors.forename: Elisa
authors.initials: E
authors.lastname: Gnappi
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
authors.forename: Landino
authors.initials: L
authors.lastname: Allegri
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.forename: Elena
authors.initials: E
authors.lastname: Bresin
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Pilato
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Valoti
authors.forename: Sonia
authors.initials: S
authors.lastname: Pasquali
authors.forename: Carlo
authors.initials: C
authors.lastname: Buzio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D065766:Atypical Hemolytic Uremic Syndrome; D003165:Complement System Proteins / Q000235:genetics* / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000150:complications*; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012196:Review Literature as Topic; D055815:Young Adult
chemical_list: D003165:Complement System Proteins
keywords: atypical haemolytic uraemic syndrome; glomerulonephritis; nephrotic syndrome; thrombotic microangiopathy; vasculitis