Fluvastatin in the prevention of renal transplant vasculopathy: results of a prospective, randomized, double-blind, placebo-controlled trial.
BACKGROUND
Statins prevent the progression of transplant vasculopathy in heart transplants, but its beneficial effect on the transplanted kidney is controversial.


METHODS
The aim is to evaluate the utility of fluvastatin 80 mg/day to reduce the progression of 6-month renal transplant vasculopathy in a multicenter, prospective, randomized, placebo-controlled trial stratified according to donor age. All patients received cyclosporine, mycophenolate mofetil, and prednisone. The progression of transplant vasculopathy was evaluated in paired donor and 6-month protocol biopsies. The primary efficacy variable was the progression of mean arterial intimal volume fraction (deltaVvintima/artery) evaluated with histomorphometry. The minimum sample size to detect a 50% reduction in the progression of deltaVvintima/artery was 62 patients per group. The secondary efficacy variable included the incidence of transplant vasculopathy evaluated according to Banff criteria.


RESULTS
A total of 89 patients were included, 74 completed the 6-month study and 57 have paired biopsies with sufficient tissue for histological evaluation. The deltaVvintima/artery was not different between treatment and placebo groups (6.9+/-8.2% vs. 6.9+/-7.4%, P=ns), whereas the incidence of transplant vasculopathy was lower in the fluvastatin group (7% vs. 33%; P=0.02). Because there was a discrepancy between the primary and secondary efficacy variables, post hoc analysis was performed to evaluate the reproducibility of both variables in a subset of 50 biopsies. The reproducibility of transplant vasculopathy was higher than the reproducibility of Vvintima/artery (kappa 0.86 vs. 0.33).


CONCLUSIONS
In summary, there were no differences in deltaVvintima/artery between groups, but fluvastatin treatment was associated with a reduced incidence of transplant vasculopathy.
Serón
Daniel
D
Nephrology Department, Hospital Universitari Bellvitge, Barcelona, Spain. 17664dsm@comb.es
Oppenheimer
Federico
F
Pallardó
Luis M
LM
Lauzurica
Ricardo
R
Errasti
Pedro
P
Gomez-Huertas
Ernesto
E
Bosmans
Jean Louis
JL
Sanchez-Plumed
Jaime
J
Romero
Rafael
R
Marques
María
M
Fulladosa
Xavier
X
Moreso
Francesc
F
D000328:Adult; D001530:Belgium; D001707:Biopsy, Needle; D018450:Disease Progression; D004311:Double-Blind Method; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012077:Renal Artery / Q000187:drug effects / Q000473:pathology; D015203:Reproducibility of Results; D013030:Spain; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014652:Vascular Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D007211:Indoles; D000077340:Fluvastatin