Nephrol Dial Transplant (2002) 17: 793-797
© 2002 European Renal Association-European Dialysis and Transplant Association
Do severe systemic sequelae of proteinuria modulate the antiproteinuric response to chronic ACE inhibition?
1 Departments of Clinical Pharmacology 2 Nephrology, Faculty of Medical Sciences and Groningen University Institute of Drug Exploration (GUIDE), University of Groningen, The Netherlands
Background. ACE inhibition exerts an antiproteinuric and renoprotective effect. However, residual proteinuria is often present. As residual proteinuria is associated with a poor renal outcome, identification of its determinants is important. We found previously that the systemic sequelae of proteinuria enhance renal damage in untreated nephrotic rats. The impact of systemic nephrosis on renal therapy response, however, is unclear. In the present study we therefore investigated whether the severity of systemic nephrosis, estimated from plasma cholesterol, predicts residual proteinuria during ACE inhibition.
Methods. Sixty male Wistar rats with established adriamycin nephrosis were studied. Six weeks after the induction of nephrosis, rats were stratified for proteinuria and treated for 2 weeks with lisinopril (75 mg/l) or vehicle.
Results. At the start of treatment, median proteinuria was 744 mg/day (95% confidence interval (CI) 609–860) and plasma cholesterol was 10.4 mmol/l (95% CI 8.0–12.6), reflecting the state of systemic nephrosis. Lisinopril, but not vehicle, reduced blood pressure and proteinuria (-62%; range -70 to -48; P<0.001). Residual proteinuria was 275 mg/day, with a wide range (47–1119 mg/day). Pre-treatment proteinuria and pre-treatment cholesterol correlated positively with residual proteinuria. By multivariate analysis (r2 of model =0.92), both pre-treatment cholesterol and pre-treatment proteinuria were independent predictors of residual proteinuria. The quantitative impact of this multivariate analysis is illustrated by the difference in residual proteinuria between rats with a cholesterol:proteinuria ratio less than, compared with greater than, the median (residual proteinuria 298 mg/day (CI 129–496) vs 439 mg/day (CI 158–670), respectively). Blood pressure response was not predicted by the tested predictor variables.
Conclusions. In this model of proteinuria-induced renal damage, not only proteinuria as such, but also the concomitant nephrotic alterations predict residual proteinuria. Further studies, applying specific interventions, are needed to determine which components of the systemic derangements could play a causal role in the modulation of therapy response.
Keywords: established adriamycin nephrosis; lisinopril; plasma cholesterol; proteinuria; residual proteinuria; systemic nephrosis
Correspondence and offprint requests to: G. J. Navis, Department of Nephrology, Faculty of Medical Sciences, Hanzeplein 1, NL-9713 GZ Groningen, The Netherlands. Email: g.j.navis{at}int.azg.nl
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