High water intake ameliorates tubulointerstitial injury in rats with subtotal nephrectomy: possible role of TGF-beta

Kidney Int. 1999 May;55(5):1800-10. doi: 10.1046/j.1523-1755.1999.00443.x.


Background: It has been shown that tubulointerstitial injury correlates well with a decline of renal function. In this study, we investigated the effect of high water intake (HWI) on functional and structural parameters in rats with subtotal nephrectomy.

Methods: Two weeks after the ablative procedure, rats were divided into two groups. One group received the treatment with HWI (3% sucrose added to drinking water) for eight weeks. Functional parameters were compared with sham-operated control (CONT) or nephrectomized rats without treatment (NX). Remnant kidneys were then assessed histologically for evidence of interstitial fibrosis and glomerulosclerosis.

Results: Creatinine clearance was significantly improved in HWI rats compared with NX rats. Simultaneously, urinary protein was also significantly reduced in HWI rats. HWI predominantly ameliorated interstitial lesions and, to a lesser extent, glomerular lesions. Northern blot analysis demonstrated that transforming growth factor-beta (TGF-beta) mRNA expression was significantly suppressed in HWI rats. In situ hybridization revealed that HWI suppressed TGF-beta mRNA expression mainly in the outer medulla. Fibronectin mRNA was also reduced by the HWI treatment. The changes in TGF-beta and fibronectin mRNA were in parallel with Na+/myo-inositol cotransporter (SMIT) mRNA, which is regulated by extracellular osmolarity. Immunohistochemistry demonstrated that protein expression of TGF-beta and fibronectin coincided with the mRNA expression.

Conclusion: These results suggest that HWI reduces TGF-beta mRNA expression in medullary interstitium and ameliorates tubulointerstitial injury in rats with reduced renal mass.

MeSH terms

  • Animals
  • Blood Pressure
  • Blotting, Northern
  • Carrier Proteins / genetics
  • DNA, Complementary
  • Drinking / physiology*
  • Fibronectins / genetics
  • Gene Expression / immunology
  • Glomerulosclerosis, Focal Segmental / immunology
  • Glomerulosclerosis, Focal Segmental / surgery
  • Glomerulosclerosis, Focal Segmental / therapy
  • Heat-Shock Proteins / genetics
  • Hypertonic Solutions / pharmacology
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Male
  • Membrane Proteins*
  • Nephrectomy*
  • Nephritis, Interstitial / immunology
  • Nephritis, Interstitial / surgery
  • Nephritis, Interstitial / therapy*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Symporters*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Water / pharmacology*


  • Carrier Proteins
  • DNA, Complementary
  • Fibronectins
  • Heat-Shock Proteins
  • Hypertonic Solutions
  • Membrane Proteins
  • RNA, Messenger
  • Symporters
  • Transforming Growth Factor beta
  • Water
  • SLC5A3 protein, human