title: Effects of dietary salt restriction on renal progression and interstitial fibrosis in adriamycin nephrosis.
abstract: OBJECTIVE
  Although high salt intake is thought to accelerate renal progression in proteinuric kidney disease, it is not known whether strict dietary salt restriction could delay renal inflammation and interstitial fibrosis. Here, we sought to answer this question in a rat model of adriamycin-induced nephrotic syndrome.
  
  
  METHODS
  Adriamycin was administered via the femoral vein in a single bolus (7.5 mg/kg), and the rats were put on a sodium-deficient rodent diet. Rats with intact kidneys were studied for 5 weeks (experiment 1), and uninephrectomized rats were studied for 6 weeks (experiment 2).
  
  
  RESULTS
  In experiment 1, restricting salt intake improved renal tubulointerstitial histopathology in adriamycin-treated rats. Immunohistochemical and immunoblot results additionally showed that restricting dietary salt lowered adriamycin-induced expression of osteopontin, collagen III, and fibronectin. In experiment 2, salt restriction improved adriamycin-induced azotemia, although it did not affect proteinuria or blood pressure. Dietary salt restriction also reduced adriamycin-induced infiltration of ED1-positive cells and the upregulated expression of osteopontin and α-SMA. Masson's trichrome and Sirius red staining revealed that salt restriction slowed Adriamycin-induced progression of renal interstitial fibrosis. Finally, qPCR revealed that adriamycin-induced expression of TNF-α, IκB-α, gp91(phox), p47(phox), and p67(phox) mRNA was blocked by salt restriction.
  
  
  CONCLUSIONS
  Our findings demonstrate that strict dietary salt restriction delays the progress of renal inflammation and fibrosis in proteinuric kidney disease, most likely via relieving the reactive oxygen species-mediated NF-κB activation.
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Joon-Sung
authors.initials: JS
authors.lastname: Park
authors.forename: Sua
authors.initials: S
authors.lastname: Kim
authors.forename: Chor Ho
authors.initials: CH
authors.lastname: Jo
authors.forename: Il Hwan
authors.initials: IH
authors.lastname: Oh
authors.forename: Gheun-Ho
authors.initials: GH
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D024061:Collagen Type III / Q000378:metabolism; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D018450:Disease Progression; D004317:Doxorubicin / Q000009:adverse effects*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009401:Nephrosis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D053495:Osteopontin / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
chemical_list: D000199:Actins; D024061:Collagen Type III; D005353:Fibronectins; D016328:NF-kappa B; D017673:Sodium Chloride, Dietary; D053495:Osteopontin; D004317:Doxorubicin