Lenka Sedláková1,2, Věra Čertíková Chábová3, Šárka Doleželová1,2, Petra Škaroupková1, Libor Kopkan1, Zuzana Husková1, Lenka Červenková1,4, Soňa Kikerlová1, Ivana Vaněčková5, Janusz Sadowski6, Elzbieta Kompanowska-Jezierska6, Petr Kujal1,4, Herbert J Kramer7, Luděk Červenka1,8. 1. a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic. 2. b Department of Physiology, Faculty of Science , Charles University , Prague , Czech Republic. 3. c Department of Nephrology, 1st Faculty of Medicine , Charles University , Prague , Czech Republic. 4. f Department of Pathology, 3rd Faculty of Medicine , Charles University , Prague , Czech Republic. 5. d Institute of Physiology, v.v.i., Academy of Sciences of the Czech Republic , Prague , Czech Republic. 6. e Department of Renal and Body Fluid Physiology , Mossakowski Medical Research Center, Polish Academy of Sciences , Warsaw , Poland. 7. g Section of Nephrology, Medical Policlinic, Department of Medicine , University of Bonn , Bonn , Germany. 8. h Department of Pathophysiology, 2nd Faculty of Medicine , Charles University , Prague , Czech Republic.
Abstract
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.
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 hypertensiverats (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.
Authors: Věra Čertíková Chábová; Petr Kujal; Petra Škaroupková; Zdeňka Varňourková; Šárka Vacková; Zuzana Husková; Soňa Kikerlová; Janusz Sadowski; Elzbieta Kompanowska-Jezierska; Iwona Baranowska; Sung Hee Hwang; Bruce D Hammock; John D Imig; Vladimír Tesař; Ludek Červenka Journal: Kidney Blood Press Res Date: 2018-03-06 Impact factor: 2.687
Authors: Onju Ham; William Jin; Lei Lei; Hui Hui Huang; Kenji Tsuji; Ming Huang; Jason Roh; Anthony Rosenzweig; Hua A Jenny Lu Journal: Sci Rep Date: 2018-10-31 Impact factor: 4.379