title: De novo thrombotic microangiopathy after kidney transplantation: clinical features, treatment, and long-term patient and graft survival.
abstract: BACKGROUND
  Posttransplant thrombotic microangiopathy (TMA)/hemolytic uremic syndrome (HUS) can occur as a recurrent or de novo disease.
  
  
  METHODS
  A retrospective single-center observational study was applied in order to examine the incidence and outcomes of de novo TMA/HUS among transplantations performed between 2000 and 2010. Recurrent HUS or antibody-mediated rejections were excluded.
  
  
  RESULTS
  Seventeen (1.1%) among 1549 kidney transplant recipients fulfilled criteria for de novo TMA. The mean follow-up was 572 days (range, 69-1769). Maintenance immunosuppression was prednisone, tacrolimus (TAC), and mycophenolic acid in 14 (82%) patients. Mean age at onset was 40 ± 15 years, and serum creatinine was 6.1 ± 4.1 mg/dL. TMA occurred at a median of 25 days (range, 1-1755) after transplantation. Nine (53%) patients developed TMA within 1 month of transplantation and only 12% after 1 year. Clinical features were anemia (hemoglobin < 10 g/dL) in 9 (53%) patients, thrombocytopenia in 7 (41%), and increased lactate dehydrogenase in 12 (70%). Decreased haptoglobin was observed in 64% and schistocytes in 35%. Calcineurin inhibitor (CNI) withdrawal or reduction was the first step in the management of 10/15 (66%) patients, and 6 (35%) received fresh frozen plasma (FFP) and/or plasmapheresis. TAC was successfully reintroduced in six patients after a median of 17 days. Eight (47%) patients needed dialytic support after TMA diagnosis and 75% remained on dialysis. At 4 years of follow-up, death-censored graft survival was worse for TMA group (43.0% versus 85.6%, log-rank = 0.001; hazard ratio = 3.74) and there was no difference in patient survival (53.1% versus 82.2%, log-rank = 0.24).
  
  
  CONCLUSIONS
  De novo TMA after kidney transplantation is a rare but severe condition with poor graft outcomes. This syndrome may not be fully manifested, and clinical suspicion is essential for early diagnosis and treatment, based mainly in CNI withdrawal and FFP infusions and/or plasmapheresis.
authors.affiliation: Nephrology Division, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: R A
authors.initials: RA
authors.lastname: Caires
authors.forename: I D B
authors.initials: ID
authors.lastname: Marques
authors.forename: L P
authors.initials: LP
authors.lastname: Repizo
authors.forename: V A H
authors.initials: VA
authors.lastname: Sato
authors.forename: L P F
authors.initials: LP
authors.lastname: Carmo
authors.forename: D J B
authors.initials: DJ
authors.lastname: Machado
authors.forename: F J
authors.initials: FJ
authors.lastname: de Paula
authors.forename: W C
authors.initials: WC
authors.lastname: Nahas
authors.forename: E
authors.initials: E
authors.lastname: David-Neto
mesh_terms: D000328:Adult; D016913:Blood Component Transfusion; D057915:Drug Substitution; D042241:Early Diagnosis; D005260:Female; D006085:Graft Survival; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D057049:Thrombotic Microangiopathies / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents