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Renin-angiotensin system blockade alone or combined with ETA receptor blockade: effects on the course of chronic kidney disease in 5/6 nephrectomized Ren-2 transgenic hypertensive rats

L. Sedláková, V. Čertíková Chábová, Š. Doleželová, P. Škaroupková, L. Kopkan, Z. Husková, L. Červenková, S. Kikerlová, I. Vaněčková, J. Sadowski, E. Kompanowska-Jezierska, P. Kujal, HJ. Kramer, L. Červenka,

. 2017 ; 39 (2) : 183-195. [pub] 20170301

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc17023214

Grant support
NV15-28671A MZ0 CEP Register

BACKGROUND: Early addition of endothelin (ET) type A (ETA) receptor blockade to complex renin-angiotensin system (RAS) blockade has previously been shown to provide better renoprotection against progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). In this study, we examined if additional protection is provided when ETA blockade is applied in rats with already developed CKD. METHODS: For complex RAS inhibition, an angiotensin-converting enzyme inhibitor along with angiotensin II type 1 receptor blocker was used. Alternatively, ETA receptor blocker was added to the RAS blockade. The treatments were initiated 6 weeks after 5/6 NX and the follow-up period was 50 weeks. RESULTS: When applied in established CKD, addition of ETA receptor blockade to the complex RAS blockade brought no further improvement of the survival rate (30% in both groups); surprisingly, aggravated albuminuria (588 ± 47 vs. 245 ± 38 mg/24 h, p < 0.05) did not reduce renal glomerular injury index (1.25 ± 0.29 vs. 1.44 ± 0.26), did not prevent the decrease in creatinine clearance (203 ± 21 vs. 253 ± 17 μl/min/100 g body weight), and did not attenuate cardiac hypertrophy to a greater extent than observed in 5/6 NX TGR treated with complex RAS blockade alone. CONCLUSIONS: When applied in the advanced phase of CKD, addition of ETA receptor blockade to the complex RAS blockade brings no further beneficial renoprotective effects on the CKD progression in 5/6 NX TGR, in addition to those seen with RAS blockade alone.

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$a Čertíková Chábová, Věra $u c Department of Nephrology, 1st Faculty of Medicine , Charles University , Prague , Czech Republic.
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$a Kikerlová, Soňa $u a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.
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$a Sadowski, Janusz $u e Department of Renal and Body Fluid Physiology , Mossakowski Medical Research Center, Polish Academy of Sciences , Warsaw , Poland.
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$a Kompanowska-Jezierska, Elzbieta $u e Department of Renal and Body Fluid Physiology , Mossakowski Medical Research Center, Polish Academy of Sciences , Warsaw , Poland.
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