Lely A Titia, van der Kleij Frank G H, Kistemaker Taco J, Apperloo Alfred J, de Jong Paul E, de Zeeuw Dick, Navis Gerjan
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands.
Clin J Am Soc Nephrol. 2008 Jan;3(1):54-60. doi: 10.2215/CJN.01450307. Epub 2007 Dec 12.
Randomized clinical trials on progression of renal diseases usually include patients according to criteria for BP, renal function, and proteinuria. There are no data showing that this provides groups with similar baseline rates of renal function loss. Accordingly, the impact of preintervention rate of renal function loss (slope) on outcome of studies has not been established.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Preintervention slope was established in 60 of 89 renal patients without diabetes in whom a 4-yr prospective, randomized intervention had been performed (enalapril versus atenolol), and whether (1) preintervention slope was distributed equally over the groups; (2) treatment benefit, defined as slope improvement, corresponded to study outcome; and (3) preintervention slope was a determinant of intervention slope were analyzed.
The preintervention slope was different in the groups: -3.7 +/- 3.2 in the group to receive enalapril versus -2.2 +/- 3.3 ml/min per yr in the group to receive atenolol. The intervention slopes were similar: -1.9 +/- 0.8 enalapril and -1.8 +/- 0.7 ml/min per yr atenolol. Accordingly, slope improved during enalapril only. When analyzed by angiotensin-converting enzyme (I/D) genotype, slope improvement was found only in DD genotype. On multivariate analysis, the preintervention slope was a main predictor of the intervention slope.
Differences in preintervention slope are relevant to outcome of trials and can induce bias. For future studies, allocation according to preintervention slope, although time-consuming, may be useful to allow conduction of more valid studies in a smaller number of patients.
关于肾脏疾病进展的随机临床试验通常根据血压、肾功能和蛋白尿标准纳入患者。尚无数据表明这样分组能使各研究组的肾功能丧失基线率相似。因此，干预前肾功能丧失率（斜率）对研究结果的影响尚未明确。
设计、地点、参与者及测量方法：在89例非糖尿病肾病患者中有60例患者建立了干预前斜率，这些患者接受了为期4年的前瞻性随机干预（依那普利与阿替洛尔对照），并分析了以下内容：（1）干预前斜率在各研究组中的分布是否均匀；（2）治疗获益（定义为斜率改善）是否与研究结果相符；（3）干预前斜率是否为干预斜率的决定因素。
各研究组的干预前斜率不同：接受依那普利治疗组为-3.7±3.2，接受阿替洛尔治疗组为-2.2±3.3 ml/min/年。干预斜率相似：依那普利组为-1.9±0.8，阿替洛尔组为-1.8±0.7 ml/min/年。因此，仅依那普利治疗期间斜率有所改善。按血管紧张素转换酶（I/D）基因型分析时，仅在DD基因型中发现斜率改善。多因素分析显示，干预前斜率是干预斜率的主要预测因素。
干预前斜率的差异与试验结果相关且可能导致偏倚。对于未来的研究，根据干预前斜率进行分组，虽然耗时，但可能有助于在较少患者中开展更有效的研究。
