First experience with rapamycin-based immunosuppression to improve kidney function after heart transplantation.
This study was designed to gain initial experience with rapamycin in thoracic organ transplant recipients with severely compromised kidney function, i.e. to see whether and how kidney function will improve with a rapamycin-based immunosuppressive protocol.


METHODS
Twelve heart transplant patients were included into the study (serum creatinine > 2.5 mg/dL), with an average time after transplantation of more than 4 years. The calcineurin inhibitor (cyclosporine A = 9, tacrolimus = 3) was reduced by 50 %, and rapamycin added to reach a target level of 8 - 12 ng/dL. Azathioprine was halted, corticosteroid treatment remained unchanged.


RESULTS
After implementing the rapamycin-based immunosuppression kidney function improved in all patients within one week. Serum creatinine dropped from 3.1 +/- 0.6 mg/dL to 2.7 +/- 0.5 mg/dL ( p = 0.0004), creatinine clearance increased from 30.4 +/- 11 mL/min to 40.8 +/- 10.5 mL/min ( p = 0.003). This improvement continued until 3 months after the conversion ( p = 0.032). Thereafter, no statistically significant changes were noted up to 6 months posttransplant ( p = 0.41). Serum cyclosporine levels dropped from 180 +/- 40 ng/mL to 132 +/- 46 ng/mL on average ( p = 0.002). Side-effects occurred in 4 patients and were all related to a rapamycin level exceeding 12 ng/mL.


CONCLUSIONS
We conclude that transplant patients with impaired kidney function will have an immediate benefit from partially replacing calcineurin inhibitors by rapamycin.
Trösch
F
F
Department of Thoracic and Cardiovascular Surgery, University Hospital Münster, Münster, Germany.
Rothenburger
M
M
Schneider
M
M
Welp
H
H
Etz
C
C
Wilhelm
M J
MJ
Scheld
H H
HH
Schmid
C
C
D000368:Aged; D003404:Creatinine / Q000097:blood; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus