title: Differences in proteinuria and graft function in de novo sirolimus-based vs. calcineurin inhibitor-based immunosuppression in live donor kidney transplantation.
abstract: BACKGROUND
  Calcineurin inhibitor(CNI)-free protocols using sirolimus (SRL) in kidney transplantation have proven effective, although reports have linked SRL to proteinuria. We sought to investigate this link and its impact on graft function.
  
  
  METHODS
  We retrospectively analyzed 184 live donor kidney transplant recipients who exclusively received de novo CNI-based (n = 106) or SRL-based (n = 78) regimens. Estimated glomerular filtration rate (GFR) and semi-quantitative dipstick proteinuria measurements were obtained at one, six, 12, and 24 months and six and 12 months, respectively.
  
  
  RESULTS
  SRL-treated patients had higher frequencies of proteinuria (> or =1+) at 6 months (40.8% vs. 21.4%, P = 0.006) and 12 months (37.8% vs. 18.4%, P = 0.004) than those treated with CNI. Independent predictors of proteinuria at 12 months were GFR at one month (OR 0.62 per 10 ml/min/1.73 m, P<0.001), delayed graft function (OR 11.5, P = 0.02), and a SRL-based regimen (OR 4.18, P=0.002). By univariable analysis, SRL vs. CNI patients had higher GFR at each point. SRL-treated patients without proteinuria had higher GFR at 12 months compared to CNI-treated patients with and without proteinuria (66 vs. 50 or 56 ml/min/1.73 m, P < 0.05). No difference in GFR was seen between SRL-treated patients with proteinuria vs. CNI-treated patients without proteinuria (57 vs. 56 ml/min/1.73 m, P > 0.05). Absence of proteinuria and a SRL-based regimen remained independently associated FS with higher GFR at 12 months by multivariable analyses.
  
  
  CONCLUSIONS
  De novo SRL-based immunosuppression is associated with a higher frequency of semi-quantitative proteinuria, however, estimated graft function at 1 year posttransplant remains superior to that of CNI-treated patients. Nevertheless, the long-term implications of these findings need to be determined.
authors.affiliation: Department of Nephrology and Hypertension, Cleveland Clinic Foundation, OH 44195, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Stephany
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Augustine
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnamurthi
authors.forename: David A
authors.initials: DA
authors.lastname: Goldfarb
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Flechner
authors.forename: William E
authors.initials: WE
authors.lastname: Braun
authors.forename: Donald E
authors.initials: DE
authors.lastname: Hricik
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Dennis
authors.forename: Emilio D
authors.initials: ED
authors.lastname: Poggio
mesh_terms: D000328:Adult; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000652:urine*; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D019703:Calcineurin; D020123:Sirolimus