Acid retention during kidney failure induces endothelin and aldosterone production which lead to progressive GFR decline, a situation ameliorated by alkali diet  Donald E. Wesson, Jan Simoni  Kidney International  Volume 78, Issue 11, Pages 1128-1135 (December 2010) DOI: 10.1038/ki.2010.348 Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 1 Bar graphs comparing effects of 2/3 surgical nephron mass reduction of the endothelin A receptor antagonist darusentan or vehicle, and of the mineralocorticoid receptor antagonist eplerenone or vehicle, on glomerular filtration rate (GFR, μl/min) in conscious Sham and nephrectomized (Nx) animals at weeks 1 and 24 after Nx. (a) Comparison of Sham and Nx. (b) Comparison of Nx given darusentan, vehicle, or neither. (c) Comparison of Nx given eplerenone, vehicle, or neither. *P<0.05 vs index value; +P<0.05 vs 1-week value within groups. Kidney International 2010 78, 1128-1135DOI: (10.1038/ki.2010.348) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 2 Bar graphs comparing effects of dietary alkali as CaHCO3 and of CaHCO3 given darusentan+eplerenone on glomerular filtration rate (GFR) (μl/min) in conscious nephrectomized (Nx) animals at weeks 1 and 24 after Nx. (a) Comparison of Nx+CaHCO3 with Nx and Nx+calcium gluconate (CaGlu) to control for dietary calcium without providing alkali. (b) Comparison of Nx+CaHCO3 with Nx given darusentan+eplerenone. *P<0.05 vs index value; +P<0.05 is 1-week value within groups. Kidney International 2010 78, 1128-1135DOI: (10.1038/ki.2010.348) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 3 Bar graphs comparing endothelin-1 (ET-1) and aldosterone (Aldo) addition to kidney cortical microdialysate in conscious animals at week 25 after 2/3 Nx. (a) Comparison of ET-1 addition in Sham and Nx. (b) Comparison of ET-1 addition among Nx given dietary alkali as CaHCO3 or non-alkalizing CaGlu with Nx given neither. (c) Comparison of Aldo addition in Sham and Nx. (d) Comparison of Aldo addition among Nx given CaHCO3 or CaGlu with those given neither salt (Nx). *P<0.05 vs index value. Kidney International 2010 78, 1128-1135DOI: (10.1038/ki.2010.348) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 4 Bar graphs showing plasma endothelin-1 (ET-1) and aldosterone (Aldo) concentrations in conscious animals at week 25 after 2/3 Nx. (a) Comparison of plasma ET-1 in Sham and Nx and (b) comparison of ET-1 addition among Nx given dietary alkali as CaHCO3 or the non-alkalizing CaGlu with Nx given neither. (c) Comparison of plasma Aldo concentration in Sham and Nx. (d) Comparison of Aldo addition among Nx given CaHCO3 or CaGlu with those given neither salt (Nx). *P<0.05 vs index value. Kidney International 2010 78, 1128-1135DOI: (10.1038/ki.2010.348) Copyright © 2010 International Society of Nephrology Terms and Conditions