title: Absence of proteinuria predicts improvement in renal function after conversion to sirolimus-based immunosuppressive regimens in lung transplant survivors with chronic kidney disease.
abstract: BACKGROUND
  Improvement in renal function has been noted in some lung allograft recipients with chronic kidney disease (CKD) converted from a calcineurin inhibitor (CNI)- to a sirolimus (SRL)-based immunosuppressive regimen. However, not all patients have such a positive response. We sought to investigate independent predictors of a favorable renal response in a cohort of lung transplant recipients.
  
  
  METHODS
  We retrospectively studied 56 lung transplant recipients with CKD, defined as a pre-conversion estimated glomerular filtration rate (eGFR) < or =60 ml/min/1.73 m(2), who had been converted to CNI-sparing regimens using SRL (CNI-free: n = 10; CNI dose reduction + SRL: n = 46). Proteinuria prior to conversion, defined as > or =1(+) on urine dipstick, was determined when available (n = 51). Changes in mean eGFR post-conversion and independent predictors of a favorable renal response, defined as a rise in eGFR > or =20% within 1 month, were investigated.
  
  
  RESULTS
  Mean eGFR at conversion was 35 +/- 14 ml/min/1.73 m(2), increasing by 8 +/- 14 ml/min/1.73 m(2) (p < 0.01) by 1 month post-conversion, a trend that remained significant out to 18 months. A total of 43% (n = 24) of patients had a rise in eGFR > or =20%. Forced expiratory volume in 1 second (FEV(1)) remained stable in survivors maintained on SRL and only 1 rejection episode occurred. When controlling for gender, age, pre-conversion eGFR and CNI-free vs CNI-dose reduction, the only variable that remained independently predictive of a favorable renal response was absence of proteinuria, with an odds ratio = 3.3 (95% confidence interval 1.0 to 12.5, p = 0.05).
  
  
  CONCLUSIONS
  Non-proteinuric lung transplant survivors with CKD are more likely to respond favorably from a renal standpoint after conversion to SRL with CNI-dose reduction or elimination.
authors.affiliation: Department of Nephrology and Hypertension, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. stephab@ccf.org
authors.forename: Brian R
authors.initials: BR
authors.lastname: Stephany
authors.forename: Mirna
authors.initials: M
authors.lastname: Boumitri
authors.forename: Marie
authors.initials: M
authors.lastname: Budev
authors.forename: Bashar
authors.initials: B
authors.lastname: Alao
authors.forename: Emilio D
authors.initials: ED
authors.lastname: Poggio
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000150:complications / Q000503:physiopathology*; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus