interindividual differences in antiproteinuric response to acei in established adriamycin nephrotic rats are predicted by pretreatment renal damage ace inhibition acei reduces proteinuria and provides renoprotection but not all subjects benefit from acei individual differences in the reduction in proteinuria at the onset of treatment and in residual proteinuria during therapy predict differences in renal outcome the present study investigated whether individual differences in the antiproteinuric efficacy of acei are explained by differences in the severity of pretreatment renal structural damage and whether differences in the level of residual proteinuria during therapy are explained by the severity of renal structural damage at that time in adriamycin nephrosis in the rat pretreatment renal structural damage was assessed in biopsies 6 weeks after exposure to adriamycin 2 mgkg iv then acei 75 mgl lisinopril n 23 or vehicle n 10 was administered renal biopsies were repeated after stabilization of the antiproteinuric response week 8 early renal damage interstitial alphasmooth muscle actin expression and macrophage accumulation and established lesions focal glomerulosclerosis fgs and interstitial fibrosis were scored during acei proteinuria fell from 834 487851 mg24 h pretreatment to 153 66265 mg24 h at week 8 p 005 fgs stabilized from 27 470 arbitrar units au pretreatment to 26 484 at week 12 whereas the vehicle did not affect proteinuria resulting in progressive fgs 18 1026 au pretreatment versus 88 46130 at week 12 p 005 all parameters of pretreatment damage significantly predicted the antiproteinuric response residual proteinuria during acei correlated significantly with renal structural damage parameters at that time pretreatment renal damage also predicted renal outcome during extended treatment thus in this experimental setting in rats with the same renal disorder and the same duration of disease individual differences in pretreatment renal damage albeit relatively modest explain individual differences in renal responsiveness to acei this implies that the limits of the efficacy of acei are set by prevalent renal damage further studies into the mechanisms of individual resistance to the antiproteinuric action of acei are needed to develop additive intervention strategies