Effect of Modification of Immunosuppressive Regimen on Renal Allograft Survival Rate in Recipients with Mild Chronic Rejection

Kim, Jeong Yoen; Ju, Man Ki; Jeong, Hyeon Joo; Ahn, Hyung Jun; Kim, Myoung Soo; Kim, Soon Il; Kim, Yu Seun

Abstract

Purpose: Concept that modification of immunosuppression can delay the deterioration of graft function and graft failure is the one of strategies for chronic rejection. We analyzed the effect of modification of immunosuppression in 116 recipients with biopsy confirmed mild chronic rejection retrospectively.
Methods
Mild chronic rejection was diagnosed by single renal pathologist under the uniformed criteria; mild tubular atrophy & interstitial fibrosis (less than 25%) combined with vascular change such as fibrous intimal thickening. General rules of modification after chronic rejection in our center were (1) strict adjustment of cyclosporine (CsA) dosage around 100~120microgram/L of trough blood level, (2) triple conversion in double therapy recipients (add anti-metabolites; azathioprine or MMF), (3) dose increment of anti-metabolites, (4) maintain of immunosuppression if ongoing immunosuppression is satisfactory to above criteria.
Results
After 74.8+/-44.5 months of follow-up, we identified 72 graft failures (62.1%). Overall post-diagnosis graft survival rate were 93.1%, 79.7%, 63.6% and 35.8% in 1, 3, 5 and 10 years respectively. The status of graft function categorizedn by stage of chronic kidney disease (CKD) at diagnosis (CKD 4 or 5 stage), timing of diagnosis (more than post-transplant 3 years) and presence of severe proteinuria (more than 1 g/day of urinary excretion) were significant risk factors affecting the post-diagnosis graft survival rate. In multivariate survival analysis, these factors were confirmed as independent variables affecting post-diagnosis graft survival rate. But modification of immunosuppressive regimen after mild chronic rejection which was classified by modification (yes versus no), type of anti-metabolites (azathioprine versus MMF) and change of immunosuppressive strength (equal versus additional versus incremental) didn't cause the significant difference of post-diagnosis graft survival rate.
Conclusion
Though pathologic change is mild, the modification of immunosuppression is not effective to delay graft failure in renal allograft recipient with pathologically established chronic rejection.