Skip to main content
Log in

Vitamin E administration at the onset of fever prevents renal scarring in acute pyelonephritis

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

We evaluated the protective effects of antioxidant at the onset of fever on renal damage in a rat model of acute pyelonephritis. Twenty rats were allocated to four groups. In groups 1 to 3, the animals were given direct inoculation of Escherichia coli into the right kidney, and group four served as control. All rats in groups 1 to 3 were given once-daily intraperitoneal injections of ceftriaxon for five consecutive days, beginning on the third day after inoculation. The animals’ body temperatures were monitored; as soon as body temperature reaches 38°C, the rats in group 2 were given allopurinol co-treatment, whereas, in group 3, vitamin E co-treatment was started at fever onset. Both kidneys were excised 6 weeks later, for the evaluation of histopathologic changes, apoptotic damage, and concentrations of transforming growth factor-beta (TGF-β). Only minimal changes were found in control samples. Pathologic scores of inflammation and fibrosis in group 1 were higher than in the vitamin E and allopurinol groups (P < 0.05). Apoptosis index was also decreased in groups 2 and 3, compared to group 1 (P < 0.05). There was no significant difference in average TGF-β levels between study groups. These findings suggest that administration of vitamin E or allopurinol following the onset of fever can reduce renal damage in pyelonephritis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

APN:

acute pyelonephritis

E. coli :

Escherichia coli

UTI:

urinary tract infection

EIA:

enzyme immunosorbent assay

TGF-β:

transforming growth factor-beta

TUNEL:

terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling

References

  1. Glauser MP, Meylan P, Bille J (1987) The inflammatory response and tissue damage. Pediatr Nephrol 1:615–619

    Article  CAS  Google Scholar 

  2. Roberts JA, Kaack MB, Baskin G (1990) Treatment of experimental pyelonephritis in the monkey. J Urol 143:150–154

    Article  CAS  Google Scholar 

  3. Pohl HG, Rushton HG, Park J, Chandra R, Majd M (1999) Adjunctive oral corticosteroids reduce renal scarring: The piglet model of reflux and acute experimental pyelonephritis. J Urol 162:815–820

    Article  CAS  Google Scholar 

  4. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L (2006) Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. J Pediatr 117:626–632

    Article  Google Scholar 

  5. Haraoka M, Matsumoto T, Takahashi K, Kubo S, Tanaka M, Kumazawa J (1994) Suppression of renal scarring by prednisolone combined with ciprofloxacin in ascending pyelonephritis in rats. J Urol 151:1078–1080

    Article  CAS  Google Scholar 

  6. Huang A, Palmer LS, Hom D, Anderson AE, Leslie K, Israel F (1999) Ibuprofen combined with antibiotics suppresses renal scarring due to ascending pyelonephritis in rats. J Urol 162:1396–1398

    Article  CAS  Google Scholar 

  7. LeBrun M, Grenier L, Gourde P, Bergeron MG, Labrecque G, Beauchamp D (1999) Effectiveness and toxicity of gentamicin in an experimental model of pyelonephritis: effect of the time of administration. Antimicrob Agents Chemother 43:1020–1026

    Article  CAS  Google Scholar 

  8. Kavukcu S, Soylu A, Turkmen M, Sarioglu S, Buyukgebiz B, Gure A (1999) The role of vitamin A in preventing renal scarring secondary to pyelonephritis. BJU Int 83:1055–1059

    Article  CAS  Google Scholar 

  9. McLorie GA, McKenna PH, Jumper BM (1990) High grade vesicourethral reflux: analysis of observational therapy. J Urol 144:537–545

    Article  CAS  Google Scholar 

  10. Roberts JA, Kaack MB, Fussell EN, Baskin G (1986) Immunology of pyelonephritis VII. Effect of allopurinol. J Urol 136:660–663

    Article  Google Scholar 

  11. Singal AK, Bajpai M, Dinda AK (2005) Blockade of rennin–angiotensin system blunts the fibrotic response in experimental acute pyelonephritis. J Indian Assoc Pediatr Surg 10:20–24

    Article  Google Scholar 

  12. Yagmurlu A, Boleken ME, Etory D, Ozsan M, Gokcora IH, Dindar H (2003) Preventive effect of pentoxifylline on renal scarring in rat model of pyelonephritis. J Urol 61:1037–1041

    Article  Google Scholar 

  13. Bennett RT, Mazzaccaro RJ, Chopra N, Melman A, Israel F (1999) Suppression of renal inflammation with vitamin A and E in ascending pyelonephritis in rats. J Urol 161:1681–1684

    Article  CAS  Google Scholar 

  14. Serlachius E, Sundelin B, Eklöf AC, Jahnke M, Laestadius A, Aperia A (1997) Pyelonephritis provokes growth retardation and apoptosis in infant rat renal cortex. Kidney Int 51:1855–1862

    Article  CAS  Google Scholar 

  15. Kannan K, Jain SK (2000) Oxidative stress and apoptosis. Pathophysiology 7:153–163

    Article  CAS  Google Scholar 

  16. Zhang D, Okada S, Yu Y, Zheng P, Yamaguchi R, Kasai H (1997) Vitamin E inhibits apoptosis, DNA modification, and cancer incidence induced by iron-mediated peroxidation in Wistar rat kidney. Cancer Res 57:2410–2414

    CAS  PubMed  Google Scholar 

  17. Kaye D (1971) The effect of water diuresis on spread of bacteria through the urinary tract. J Infect Dis 124:297–305

    Article  CAS  Google Scholar 

  18. Yasunaga Y, Kato H, Ohgaki K, Inamoto T, Hikasa Y (1982) Effect of vitamin E as an immunopotentiation agent for mice at optimal dosage and its toxicity at high dosage. J Nutr 112:1075–1084

    Article  CAS  Google Scholar 

  19. Payabvash S, Kajbafzadeh A, Tavangar S, Monajemzadeh M, Sadeghi Z (2007) Myocyte apoptosis in primary obstructive megaureters: the role of decreased vascular and neural supply. J Urol 178:259–264

    Article  Google Scholar 

  20. Chiou YY, Wang ST, Tang MJ, Lee BF, Chiu NT (2001) Renal fibrosis: prediction from acute pyelonephritis focus volume measured at 99mTc dimercaptosuccinic acid SPECT. Radiology 221:366–370

    Article  CAS  Google Scholar 

  21. Fretzayas A, Moustaki M, Gourgiotis D, Bossios A, Koukoutsakis P, Stavrinadis C (2000) Polymorphonuclear elastase as a diagnostic marker of acute pyelonephritis in children. J Pediatr 105:28–35

    Article  Google Scholar 

  22. Pecile P, Miorin E, Romanello C, Falleti E, Valent F, Giacomuzzi F, Tenore A (2004) Procalcitonin: a marker of severity of acute pyelonephritis among children. J Pediatr 114:249–254

    Article  Google Scholar 

  23. Pinson AG, Philbrick JT, Lindbeck GH, Schorling JB (1997) Fever in the clinical diagnosis of acute pyelonephritis. Am J Emerg Med 15:148–151

    Article  CAS  Google Scholar 

  24. Lin KY, Chiu NT, Chen MJ, Lai CH, Huang JJ, Wang YT, Chiou YY (2004) Acute pyelonephritis and sequelae of renal scar in pediatric first febrile urinary tract infection. Pediatr Nephrol 18:362–365

    Article  Google Scholar 

  25. Glauser MP, Lyons JM, Braude AI (1978) Prevention of chronic experimental pyelonephritis by suppression of acute suppuration. J Clin Invest 61:403–407

    Article  CAS  Google Scholar 

  26. Imamoglu M, Cay A, Cobanoglu U, Bahat E, Karahan C, Tosun I, Sarhan H (2006) Effects of melatonin on suppression of renal scarring in experimental model of pyelonephritis. J Urol 67:1315–1319

    Article  Google Scholar 

  27. Matsumoto T, Mitzunoe Y, Ogata N, Tanaka M, Takahashi K, Kumazawa J (1992) Antioxidant effect on renal scarring following infection of mannose-sensitive-piliated bacteria. Nephron 60:210–214

    Article  CAS  Google Scholar 

  28. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890–898

    Article  CAS  Google Scholar 

  29. Canbay A, Friedman S, Gores GJ (2004) Apoptosis: the nexus of liver injury and fibrosis. Hepatology 39:273–278

    Article  Google Scholar 

  30. Fliss H, Gattinger D (1996) Apoptosis in ischemic and reperfused rat myocardium. Circ Res 79:949–956

    Article  CAS  Google Scholar 

  31. Jakobsson B, Nolstedt L, Svensson L, Söderlundh S, Berg U (1992) 99 m Technetium dimercaptosuccinic acid scan in the diagnosis of acute pyelonephritis in children: relation to clinical and radiological findings. Pediatr Nephrol 6:328–334

    Article  CAS  Google Scholar 

  32. Kucuk HF, Bingul SM, Kurt N, Kaptanoglu L, Akyol H, Torlak OA, Colak E (2006) Effect of a selective cyclooxygenase-2 inhibitor on renal scarring. Eur Surg Res 38:451–457

    Article  CAS  Google Scholar 

  33. Melis K, Vandevivere J, Hoskens C, Vervaet A, Sand A, Van Acker KJ (1992) Involvement of the renal parenchyma in acute urinary tract infection: the contribution of 99mTc-dimercaptosuccinic acid scan. Eur J Pediatr 151:536–539

    Article  CAS  Google Scholar 

  34. Rushton HG, Belman AB (1968) Vesicoureteral reflux and renal scarring. In: Holliday MA (ed) 3rd edn. Williams & Wilkins, Baltimore, pp 963–985

    Google Scholar 

  35. Verboven M, Ingels M, Delree M, Piepsz A (1990) 99mTc-DMSA scintigraphy in acute urinary tract infection in children. Pediatr Radiol 20:540–542

    Article  CAS  Google Scholar 

Download references

Acknowledgment

Special thanks to Drs. Rostambeigy, Vejdani, Elmi, Rahbar, and Salmasi, and to Miss Aligholy and Mr. Farzaneh, for their kind help.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Abdol-Mohammad Kajbafzadeh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sadeghi, Z., Kajbafzadeh, AM., Tajik, P. et al. Vitamin E administration at the onset of fever prevents renal scarring in acute pyelonephritis. Pediatr Nephrol 23, 1503–1510 (2008). https://doi.org/10.1007/s00467-008-0853-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-008-0853-7

Keywords

Navigation