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Titolo:
Coinhibition of immune and renin-angiotensin systems reduces the pace of glomerulosclerosis in the rat remnant kidney
Autore:
Hamar, P; Peti-Peterdi, J; Razga, Z; Kovacs, G; Heemann, U; Rosivall, L;
Indirizzi:
Semmelweis,Univ, Sch Med, Int Nephrol Res & Training Ctr, Dept Pathophysiol Semmelweis Univ Budapest Hungary H-1089 Training Ctr, Dept Pathophysiol Univ Szeged, Dept Pathol, Szeged, Hungary Univ Szeged Szeged HungaryUniv Szeged, Dept Pathol, Szeged, Hungary Univ Hosp Essen, Dept Nephrol, Essen, Germany Univ Hosp Essen Essen Germany Hosp Essen, Dept Nephrol, Essen, Germany
Titolo Testata:
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
, volume: 10, anno: 1999, supplemento:, 11
pagine: S234 - S238
SICI:
1046-6673(199901)10:<S234:COIARS>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAILURE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
11
Recensione:
Indirizzi per estratti:
Indirizzo: Hamar, P Semmelweis,Univ, Sch Med, Int Nephrol Res & Training Ctr, Dept Pathophysiol Semmelweis Univ Nagyvarad Ter 4 Budapest Hungary H-1089 ophysiol
Citazione:
P. Hamar et al., "Coinhibition of immune and renin-angiotensin systems reduces the pace of glomerulosclerosis in the rat remnant kidney", J AM S NEPH, 10, 1999, pp. S234-S238

Abstract

The development of progressive glomerulosclerosis (GS) has been attributedto a number of humoral and hemodynamic factors, however, neither the exactpathomechanism nor the prevention and treatment have been clearly established. Renin-angiotensin system (RAS), interleukin-2 (IL-2)-activated T cells, systemic BP, and serum lipid levels all have been recognized as pathogenetic factors. According to our working hypothesis, a combination therapy with the inhibition of RAS and IL-2 system may be more potent in the prevention of the progression of GS than a monotherapy. After 5/6 subtotal nephrectomy, rats were treated with either the angiotensin-converting enzyme-blockerenalapril (E), the angiotensin II AT(1) receptor blocker candesartan cilexetil (CA), the IL-2 synthesis inhibitor tacrolimus (T), or a combination ofthese agents. Proteinuria, as a functional hallmark of GS, was determined regularly, and at week 16, systolic BP, plasma total cholesterol, and triglyceride (TG) levels were measured and kidneys were harvested for morphologic and immunohistochemical analysis. Combination therapy was more effective (proteinuria: CA + T: 29.3 +/- 12.8 mg/24 h, E + T: 31.3 +/- 13.0 mg/24 h; GS: CA + T: 10.7 +/- 4.1%, E + T: 8.3 +/- 4.6%, P < 0.01) than monotherapy (proteinuria: T: 49.3 +/- 17.3 mg/24 h, CA: 53.2 +/- 18.1 mg/24 h, E: 51.1 /- 26.6 mg/24 h; GS: T: 10.9 +/- 4.4%, CA: 23.8 +/- 4%, E: 14.2 +/- 5.3%, P < 0.05, with control values of proteinuria: 77.6 +/- 27.1 mg/24 h and GS:28 +/- 2.9%). The number of infiltrating ED-1 (rat macrophage marker) macrophages (T: 161.5 +/- 51.2 cells/field of view, CA: 203.6 +/- 102.3, E: 178.6 +/- 35.3, CA + T: 140.2 +/- 63.2, E + T:128.2 +/- 75.6), and CD-5+ (rat T cell marker)T lymphocytes (CA + T: 261.5 +/- 103.6, E + T: 236 +/- 94.8) was significantly reduced by the treatment protocols (controls: ED-1:356 +/- 100, CD-5: 482.9 +/- 154.5). These results indicate that an inhibition ofRAS either with angiotensin-converting enzyme or AT, receptor blockade, together with the inhibition of IL-2 synthesis, is more effective in the prevention of GS than a single treatment alone.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 20:54:04