title: Sodium intake modifies the negative prognostic value of renal damage prior to treatment with ACE inhibitors on proteinuria induced by adriamycin.
abstract: BACKGROUND
  Antiproteinuric treatment by ACE inhibition (ACEi) provides renoprotection. However, resistance to antiproteinuric intervention occurs frequently, resulting in progressive renal damage. The extent of renal damage prior to treatment with ACEi reversely correlates with the antiproteinuric effects of ACEi in established adriamycin nephrosis. Sodium restriction enhances the response to ACEi, but whether it can overcome the negative predictive value of preceding renal damage on the therapeutic response is unknown. We studied the impact of preceding renal damage on the efficacy of ACEi in adriamycin nephrosis on different oral sodium loads.
  
  
  METHODS
  Male Wistar rats were randomly assigned to a low (LS), normal (NS) or high (HS) sodium diet, initiated 1 week before adriamycin induction. At week 6, proteinuria was stabilized (195 +/- 172 mg/24 h), a renal biopsy was performed for analysis of preceding damage and rats were instituted on lisinopril for 6 weeks until sacrifice at week 12.
  
  
  RESULTS
  ACEi reduced proteinuria in LS and NS animals. On univariate analysis, the antiproteinuric response was significantly predicted by preceding renal damage (focal glomerulosclerosis, interstitial macrophages and interstitial alpha-smooth muscle cell actin expression). On multivariate analysis, both sodium intake and preceding renal damage independently predicted residual proteinuria during ACEi (R2 model: 80% and 75% for data after 3 and 6 weeks of therapy, respectively).
  
  
  CONCLUSIONS
  Our data confirm the predictive value of pretreatment renal damage for the antiproteinuric response to ACEi, despite the fact that the renal damage prior to the ACEi was very mild. The impact of pretreatment damage on the therapeutic response, however, was overcome by low sodium. Thus, the impact of pretreatment damage does not warrant therapeutic nihilism, but rather optimization of therapy response by dietary sodium restriction. Further studies are needed to elucidate whether this also applies to more severe damage, and whether combining ACEi with low sodium diet can improve long-term renal outcome in human.
authors.affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. g.j.navis@int.umcg.nl
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Kramer
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bos
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Gerjan J
authors.initials: GJ
authors.lastname: Navis
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D004317:Doxorubicin / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D011379:Prognosis; D011507:Proteinuria / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012982:Sodium, Dietary / Q000627:therapeutic use*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D012982:Sodium, Dietary; D004317:Doxorubicin