Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-Thy-1 irreversible nephritis

Masaki Asai, Toshiaki Monkawa, Takeshi Marumo, Seiichi Fukuda, Mihoko Tsuji, Jun Yoshino, Hiroshi Kawachi, Fujio Shimizu, Matsuhiko Hayashi, Takao Saruta

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Blockade of the renin-angiotensin system has been established as a treatment for heart failure with hypertension and left ventricular hypertrophy, and for progressive kidney diseases. The present study was conducted to examine whether spironolactone, a mineralocorticold receptor antagonist, alone or in combination with cilazapril, an angiotensin converting enzyme (ACE) inhibitor, ameliorates proteinuria and renal lesions in an immune-initiated progressive nephritis model. Wistar rats were uninephrectomized 7 days before injection of anti-Thy-1 monoclonal antibody 1-22-3 to induce progressive glomerulonephritis. The nephritic rats were untreated or treated with spironolactone (400 mg/kg body weight/day), cilazapril (11 mg/kg body weight/day), or both for 10 weeks. Proteinuria was increased in the untreated rats 1 week after nephritis induction and was maintained throughout the experiment. Compared with the untreated animals (212.9± 49.2mg/day), proteinuria was significantly reduced in the spironolactone-treated group (62.0±4.0 mg/day, p=0.0046) and the cilazapril-treated group (71.8±26.0 mg/day, p=0.0048) on day 70 after antibody injection. Further reduction of proteinuria (42.4±4.5 mg/day, p=0.0019 vs. the untreated group) and less renal cortex interstitial fibrotic change (fibrosis score: 142.0±18.4 vs. 80.3±18.5 in the untreated group, p=0.0123) were detected in the spironolactone plus cilazapril-treated group. Blood pressure did not differ among the three treatment groups. In conclusion, spironolactone ameliorates proteinuria to the same degree as cilazapril, and concomitant use of spironolactone and an ACE inhibitor further suppresses renal disease progression. These data suggest that concomitant treatment with spironolactone and an ACE inhibitor has beneficial effects on immune-initiated progressive kidney disease.

Original languageEnglish
Pages (from-to)971-978
Number of pages8
JournalHypertension Research
Volume27
Issue number12
DOIs
Publication statusPublished - 2004 Dec

Fingerprint

Cilazapril
Spironolactone
Nephritis
Proteinuria
Fibrosis
Kidney
Angiotensin-Converting Enzyme Inhibitors
Kidney Diseases
Body Weight
Injections
Left Ventricular Hypertrophy
Renin-Angiotensin System
Glomerulonephritis
anti-Thy antibody
Treatment Failure
Disease Progression
Wistar Rats
Heart Failure
Monoclonal Antibodies
Blood Pressure

Keywords

  • Aldosterone
  • Angiotensin-converting enzyme inhibitor
  • Anti-Thy-1 nephritis
  • Glomerulonephritis
  • Spironolactone

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-Thy-1 irreversible nephritis. / Asai, Masaki; Monkawa, Toshiaki; Marumo, Takeshi; Fukuda, Seiichi; Tsuji, Mihoko; Yoshino, Jun; Kawachi, Hiroshi; Shimizu, Fujio; Hayashi, Matsuhiko; Saruta, Takao.

In: Hypertension Research, Vol. 27, No. 12, 12.2004, p. 971-978.

Research output: Contribution to journalArticle

Asai, Masaki ; Monkawa, Toshiaki ; Marumo, Takeshi ; Fukuda, Seiichi ; Tsuji, Mihoko ; Yoshino, Jun ; Kawachi, Hiroshi ; Shimizu, Fujio ; Hayashi, Matsuhiko ; Saruta, Takao. / Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-Thy-1 irreversible nephritis. In: Hypertension Research. 2004 ; Vol. 27, No. 12. pp. 971-978.
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