Observation of efficacy and safety of converting the calcineurin inhibitor to sirolimus in renal transplant recipients with chronic allograft nephropathy.
OBJECTIVE
The objective of this study was to evaluate the efficacy and safety of converting from a calcineurin inhibitor (CNI) to sirolimus among renal transplant recipients with chronic allograft nephropathy (CAN).


METHODS
In 16 patients with CAN, substituted sirolimus for CsA or FK506 and observed the incidence of acute rejection and changes in serum creatinine, triglycerides, cholesterol, blood uric acid, and peripheral blood leukocyte/platelet counts within 12 months. All recipients underwent an allograft biopsy before conversion. The targeted sirolimus level was 4-8 ug/L.


RESULTS
After conversion to sirolimus, the creatinine level of 7 cases decreased and the efficacy rate was (43.8%). No acute rejection occurred during the follow-up. The cases with hypercholesteremia increased from 3 to 7 after conversion; hypertriglyceridemia increased from 3 to 5; leukopenia occurred in 2; subnormal platelet counts increased from 2 to 3; and hyperuricemia increased from 6 to 7. Meanwhile, the average level of peripheral blood leukocytes obviously decreased in the first month, the average peripheral blood cholesterol increased over 12 months, but the average content of peripheral blood platelets, triglyceride and blood uric acid failed to display as statistic difference. Eight patients showed C4d deposition in peritubular capillary in graft tissue before conversion, 7 cases of whom showed no improvement in renal function. In 6 cases there was no C4d deposition in peritubular capillary in graft tissue. Only 2 of 6 cases showed no improvement in renal function. There were 6 patients whose creatinine level was <2.48 mg/dL before conversion, and renal function in 5 of them improved in a year after conversion. In contrast, among 10 patients whose blood creatinine level was >2.48 mg/dL, only 2 cases improved.


CONCLUSIONS
It is safe for patients with CAN to use substitute sirolimus for CNI; the incidence of acute rejection did not increase. In this study, 43.8% of patients showed improved renal function. The main adverse reactions after conversion to sirolimus were hypercholesteremia and decreased peripheral blood leukocytes. The serum creatinine level and the deposition of C4d in peritubular capillary were important factors influencing therapeutic efficacy.
Chen
J
J
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Li
L
L
Wen
J
J
Tang
Z
Z
Ji
S
S
Sha
G
G
Cheng
Z
Z
Sun
Q
Q
Cheng
D
D
Liu
Z
Z
D000328:Adult; D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D010976:Platelet Count; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D012449:Safety; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology* / Q000502:physiology
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D011239:Prednisolone; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus