Effect of everolimus on left ventricular hypertrophy of de novo kidney transplant recipients:  a 1 year, randomized, controlled trial.
BACKGROUND
Although conversion from calcineurin inhibitors to mammalian target of rapamycin inhibitors proved to be effective in regressing left ventricular hypertrophy (LVH) in renal transplant recipients (RTRs) with chronic allograft dysfunction, there are currently no reports of randomized trials on this issue involving de novo RTRs administered everolimus (EVL).


METHODS
This randomized, open-label, controlled trial evaluated the effect of EVL on the left ventricular mass index (LVMi) of 30 nondiabetic RTRs (21 men; age 28-65 years). Ten were allocated to EVL plus reduced-exposure cyclosporine A (CsA), and 20 to standard dose CsA. LVMi was assessed by echocardiography both at baseline and 1 year later. Blood pressure (BP), hemoglobin, serum creatinine, lipids, trough levels of immunosuppressive drugs, and daily proteinuria were also evaluated twice monthly. Antihypertensive therapy that did not include renin-angiotensin system blockers was administered to achieve BP less than or equal to 130/80 mm Hg.


RESULTS
Changes in BP were similar in the two groups (between group difference 1.2 ± 5.7 mm Hg, P=0.84 for systolic, and -1.5 ± 3.7, P=0.69, for diastolic BP), whereas LVMi significantly decreased in the EVL group alone (between group difference 9.2 ± 3.1 g/m(2.7), P=0.005), due to a reduction in both the interventricular septum and the left ventricular posterior wall thickness. EVL therapy together with baseline LVMi were the only significant predictors of LVH regression according to a multivariate model that explained 49% of the total LVMi variance (P=0.0015).


CONCLUSIONS
An immunosuppressive regimen consisting of EVL plus reduced exposure CsA proved to be effective in regressing LVH in RTRs regardless of BP, mainly by reducing left ventricular wall thickness.
Division of Nephrology, Dialysis and Transplantation, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. ernesto.paoletti@hsanmartino.it
Ernesto
E
Paoletti
Luigina
L
Marsano
Diego
D
Bellino
Paolo
P
Cassottana
Giuseppe
G
Cannella
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D016009:Chi-Square Distribution; D016572:Cyclosporine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007558:Italy; D016030:Kidney Transplantation / Q000009:adverse effects*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012307:Risk Factors; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography
D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus