Hwee-Yeong Ng1, Hung-Chun Chen, Yu-Che Tsai, Yu-Kun Yang, Chien-Te Lee. 1. Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
Abstract
BACKGROUND: Chronic metabolic acidosis is a common metabolic disturbance and its clinical impact can be severe and extensive. The role and the change of the intrarenal renin-angiotensin system (RAS) during metabolic acidosis are uncertain, and whether acidosis can evoke inflammation remains unclear. METHODS: Male Sprague-Dawley rats were fed with water containing 0.14 M NH(4)Cl to induce metabolic acidosis for 1 and 8 weeks, respectively. They were compared with animals fed with deionized water (control) and equimolar sodium chloride water (NaCl). Gene expression analysis of RAS components included renin, renin/prorenin receptor, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type 1 and 2 receptors (AT1R and AT2R). Histological examination was also performed to detect morphological change. RESULTS: Acidosis was found in 1-week NH(4)Cl-treated rats but not in the 8-week group. More than twofold proteinuria and a significant decline of glomerular filtration rate (GFR) were observed in acid-loaded rats. Compared to the control and NaCl groups, angiotensinogen, ACE, AT1R and AT2R were significantly increased in the 1-week acidosis group (all p < 0.05). Sustained increase of AT1R expression was found as NH(4)Cl was continued for 8 weeks. There was no significant change in transforming growth factor-β and nuclear factor-κB. The architecture of tubular epithelial cells was affected during our experiment. CONCLUSION: Metabolic acidosis induced proteinuria and decline of GFR in association with activation of intrarenal RAS.
BACKGROUND: Chronic metabolic acidosis is a common metabolic disturbance and its clinical impact can be severe and extensive. The role and the change of the intrarenal renin-angiotensin system (RAS) during metabolic acidosis are uncertain, and whether acidosis can evoke inflammation remains unclear. METHODS: Male Sprague-Dawley rats were fed with water containing 0.14 M NH(4)Cl to induce metabolic acidosis for 1 and 8 weeks, respectively. They were compared with animals fed with deionized water (control) and equimolar sodium chloridewater (NaCl). Gene expression analysis of RAS components included renin, renin/prorenin receptor, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type 1 and 2 receptors (AT1R and AT2R). Histological examination was also performed to detect morphological change. RESULTS:Acidosis was found in 1-week NH(4)Cl-treated rats but not in the 8-week group. More than twofold proteinuria and a significant decline of glomerular filtration rate (GFR) were observed in acid-loaded rats. Compared to the control and NaCl groups, angiotensinogen, ACE, AT1R and AT2R were significantly increased in the 1-week acidosis group (all p < 0.05). Sustained increase of AT1R expression was found as NH(4)Cl was continued for 8 weeks. There was no significant change in transforming growth factor-β and nuclear factor-κB. The architecture of tubular epithelial cells was affected during our experiment. CONCLUSION:Metabolic acidosis induced proteinuria and decline of GFR in association with activation of intrarenal RAS.
Authors: Casey M Rebholz; Josef Coresh; Morgan E Grams; Lyn M Steffen; Cheryl A M Anderson; Lawrence J Appel; Deidra C Crews Journal: Am J Nephrol Date: 2016-01-21 Impact factor: 3.754
Authors: Kalani L Raphael; Rachel A Murphy; Michael G Shlipak; Suzanne Satterfield; Hunter K Huston; Anthony Sebastian; Deborah E Sellmeyer; Kushang V Patel; Anne B Newman; Mark J Sarnak; Joachim H Ix; Linda F Fried Journal: Clin J Am Soc Nephrol Date: 2016-01-14 Impact factor: 8.237
Authors: Casey M Rebholz; Deidra C Crews; Morgan E Grams; Lyn M Steffen; Andrew S Levey; Edgar R Miller; Lawrence J Appel; Josef Coresh Journal: Am J Kidney Dis Date: 2016-08-09 Impact factor: 8.860