Background and objectives: 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.Results: 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.Conclusions: 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.