Factors associated with progression of interstitial fibrosis in renal transplant patients receiving tacrolimus and mycophenolate mofetil.
BACKGROUND
We recently reported a randomized study in renal transplant patients (RTP) receiving tacrolimus, mycophenolate mofetil, and prednisone in which patients who had early protocol biopsies (PBx) derived no benefit compared with controls (no PBx) at 6 months, likely due to the low prevalence of subclinical rejection. We report on the follow-up of these patients to 24 months at which time a repeat PBx and tests of renal function were performed.


METHODS
Of the 240 RTP randomized, 22 were excluded for a protocol violation. Approximately 75% of the remaining 218 (111 PBx and 107 controls) completed the study.


RESULTS
At 24 months, graft function was excellent with a mean creatinine clearance of approximately 74 mL/min and negligible proteinuria; however, the prevalence of interstitial fibrosis and tubular atrophy (IF/TA)-ci + ct more than or equal to 2-increased from approximately 3% at baseline to up to 40% to 50%. By logistic regression analysis, the only independent positive correlate of IF/TA was transplantation with a deceased donor. However, by post hoc analysis, use of angiotensin-II-converting enzyme inhibitors or angiotensin II receptor blockers was negatively correlated with both the prevalence of IF/TA at 24 months and its progression between 6 and 24 months in RTP that had paired biopsies.


CONCLUSIONS
A regimen of tacrolimus, mycophenolate mofetil, and prednisone results in excellent renal function at 24 months posttransplant but with a progressive increase in IF/TA. A potential inhibitory effect of angiotensin-II-converting enzyme inhibitor/angiotensin II receptor blockers on IF/TA is suggested that requires confirmation in a randomized study.
Rush
David N
DN
Department of Internal Medicine, Health Sciences Centre, Winnipeg, MB, Canada R3A 1R9. drush@exchange.hsc.mb.ca
Cockfield
Sandra M
SM
Nickerson
Peter W
PW
Arlen
Dianne J
DJ
Boucher
Anne
A
Busque
Stephan
S
Girardin
Catherine E
CE
Knoll
Gregory A
GA
Lachance
Jean-Guy
JG
Landsberg
David N
DN
Shapiro
R Jean
RJ
Shoker
Ahmed
A
Yilmaz
Serdar
S
D000328:Adult; D001706:Biopsy; D002102:Cadaver; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D006084:Graft Rejection / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D019520:Living Donors / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D012044:Regression Analysis; D016559:Tacrolimus / Q000009:adverse effects* / Q000627:therapeutic use; D014019:Tissue Donors / Q000706:statistics & numerical data
D006680:HLA Antigens; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus