mTOR inhibitors: do they help preserve renal function?
BACKGROUND
Renal function deterioration is one of the main problems facing heart transplant recipients. The mammalian target of rapamycin (mTOR) inhibitors, in combination with or replacing calcineurin inhibitors, may help preserve renal function. The aim of this study was to evaluate the progression of renal function after switching the immunosuppressive regimen.


METHODS
We studied 23 heart transplant recipients (5.5 +/- 4.5 years since transplantation). An mTOR inhibitor was introduced to replace cyclosporine (everolimus, 65%; sirolimus, 35%). Patient clinical characteristics and renal function were studied after switching. The statistical analysis used Student t test for paired data.


RESULTS
The reason for the transplantation was ischemic cardiopathy (52%), dilated myocardiopathy (39%), or other causes (9%). Mean age at time of transplantation was 52 +/- 9 years. Comorbidities were as follows hypertension (43%), insulin-dependent diabetes (22%), hypercholesterolemia (39%), and ex-smokers (70%). The reason for the switch was increased creatinine (65%), appearance of tumors (26%), or others (8%). Previous creatinine level was 1.89 +/- 0.6 mg/dL with clearance of 61.7 +/- 23 mL/min and at the end of follow-up (mean follow-up, 11 +/- 6 months) creatinine level was 2.0 +/- 1.45 mg/dL with clearance of 68.3 +/- 35 mL/min, namely, no significant difference (P = .49 and P = .57, respectively). In the subgroup of patients who switched treatment due to renal dysfunction, initial creatinine level was 2.38 +/- 0.4 mg/dL with clearance of 42.3 +/- 10 mL/min and at the end of follow-up it was 2.28 +/- 0.2 mg/dL and 43.6 +/- 11 mL/min, respectively (P = .68 for creatinine and clearance).


CONCLUSIONS
The introduction of mTOR inhibitors to the immunosuppressant regimen may be useful to delay renal functional deterioration caused by calcineurin inhibitors.
Moro
J
J
Cardiac Failure and Transplant Unit, Cardiology Service, Valencia, Spain. moro@uv.es
Almenar
L
L
Martínez-Dolz
L
L
Agüero
J
J
Rueda
J
J
Arnau
M A
MA
Izquierdo
M
M
Cano
O
O
Sánchez-Lázaro
I
I
Salvador
A
A
D000328:Adult; D009202:Cardiomyopathies / Q000601:surgery*; D002311:Cardiomyopathy, Dilated / Q000601:surgery; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011494:Protein Kinases / Q000502:physiology*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
D007166:Immunosuppressive Agents; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus