title: Proteinuria following sirolimus conversion is associated with deterioration of kidney function in liver transplant recipients.
abstract: BACKGROUND
  The role of sirolimus (SRL) conversion in the preservation of kidney function in liver transplant (LT) recipients with calcineurin inhibitor (CNI) nephrotoxicity is unclear.
  
  
  METHODS
  Data on 102 LT recipients with deteriorating kidney function after CNI exposure who were later converted to SRL were retrospectively reviewed. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR) at time of conversion and serially thereafter. The primary endpoint was stabilization or improvement of kidney function as assessed by eGFR at last recorded follow-up compared with eGFR at the time of conversion.
  
  
  RESULTS
  After a median (interquartile range) of 3.1 (1.6-4.5) years of follow-up, serum creatinine decreased from 1.9 ± 0.8 to 1.8 ± 0.7 mg/dL (P=0.25) and eGFR increased from 40.8 ± 16.7 to 44.3 ± 20.0 mL/min (P=0.03). During the same time period, 24-hr urinary protein excretion increased from median (interquartile range) of 72 (0-155) to 382 (169-999) mg/day (P=0.0001). Sixty-five (64%) patients achieved the primary endpoint and 37 (36%) experienced deterioration in kidney function. Independent predictors of deterioration of kidney function after SRL conversion were development of proteinuria ≥ 1000 mg/day (odds ratio [OR]: 3.3, confidence interval [CI]: 1.1-9.5 P=0.03), post-LT diabetes (OR: 4.2, CI: 1.6-11.1, P=0.004), and higher eGFR at time of conversion (OR: 1.6, CI: 1.2-2.2, P=0.003).
  
  
  CONCLUSIONS
  Improvement or stabilization of kidney function occurred in the majority of LT recipients converted to SRL for CNI nephrotoxicity. Proteinuria ≥ 1000 mg/day, post-LT diabetes, and higher baseline eGFR were independent predictors of kidney function loss after SRL conversion.
authors.affiliation: Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224, USA. wadei.hani@mayo.edu
authors.forename: Hani M
authors.initials: HM
authors.lastname: Wadei
authors.forename: Ziad S
authors.initials: ZS
authors.lastname: Zaky
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Keaveny
authors.forename: Barry
authors.initials: B
authors.lastname: Rosser
authors.forename: Melanie
authors.initials: M
authors.lastname: Jones
authors.forename: Martin L
authors.initials: ML
authors.lastname: Mai
authors.forename: Ilynn
authors.initials: I
authors.lastname: Bulatao
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Gonwa
mesh_terms: D000368:Aged; D065095:Calcineurin Inhibitors; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000139:chemically induced*; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus