Serón Daniel, Oppenheimer Federico, Pallardó Luis M, Lauzurica Ricardo, Errasti Pedro, Gomez-Huertas Ernesto, Bosmans Jean Louis, Sanchez-Plumed Jaime, Romero Rafael, Marques María, Fulladosa Xavier, Moreso Francesc
Nephrology Department, Hospital Universitari Bellvitge, Barcelona, Spain.
Transplantation. 2008 Jul 15;86(1):82-7. doi: 10.1097/TP.0b013e318174428d.
Statins prevent the progression of transplant vasculopathy in heart transplants, but its beneficial effect on the transplanted kidney is controversial.
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.
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).
In summary, there were no differences in deltaVvintima/artery between groups, but fluvastatin treatment was associated with a reduced incidence of transplant vasculopathy.
他汀类药物可预防心脏移植中移植血管病变的进展，但其对移植肾的有益作用存在争议。
目的是在一项多中心、前瞻性、随机、安慰剂对照试验中，根据供体年龄分层，评估每日80毫克氟伐他汀对减少6个月肾移植血管病变进展的效用。所有患者均接受环孢素、霉酚酸酯和泼尼松治疗。在配对的供体活检和6个月方案活检中评估移植血管病变的进展。主要疗效变量是用组织形态计量学评估的平均动脉内膜体积分数（ΔVv内膜/动脉）的进展。检测ΔVv内膜/动脉进展减少50%所需的最小样本量为每组62例患者。次要疗效变量包括根据班夫标准评估的移植血管病变的发生率。
共纳入89例患者，74例完成了6个月的研究，57例有配对活检且有足够组织进行组织学评估。治疗组和安慰剂组之间的ΔVv内膜/动脉无差异（6.9±8.2%对6.9±7.4%，P=无统计学意义），而氟伐他汀组移植血管病变的发生率较低（7%对33%；P=0.02）。由于主要和次要疗效变量之间存在差异，进行了事后分析以评估50例活检子集中两个变量的可重复性。移植血管病变的可重复性高于Vv内膜/动脉的可重复性（kappa 0.86对0.33）。
总之，各组之间的ΔVv内膜/动脉无差异，但氟伐他汀治疗与移植血管病变发生率降低相关。
