Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury

Shun Yang Cheng, Yu Hsiang Chou, Fang Ling Liao, Chun Chi Lin, Fan-Chi Chang, Chia Hao Liu, Tao Min Huang, Chun Fu Lai, Yu Feng Lin, Vin Cent Wu, Tzong Shinn Chu, Ming Shiou Wu, Shuei Liong Lin

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Abstract

Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury. Despite functional recovery, focal tubular atrophy, interstitial cell infiltration and fibrosis, upregulation of genes encoding angiotensinogen and AT1a receptor were shown in kidneys 4 weeks after AKI. Thereafter mice manifested increase of blood pressure, albuminuria and azotemia progressively. Drinking water with or without losartan or hydralazine was administered to mice from 4 weeks after AKI. Increase of mortality, blood pressure, albuminuria, azotemia and kidney fibrosis was noted in mice with vehicle administration during the 5-month experimental period. On the contrary, these parameters in mice with losartan administration were reduced to the levels shown in control group. Hydralazine did not provide similar beneficial effect though blood pressure was controlled. These findings demonstrate that losartan can reduce ensuing CKD and mortality after functional recovery from AKI.

Original languageEnglish
Article number34265
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Sep 28 2016

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Losartan
Chronic Renal Insufficiency
Acute Kidney Injury
Mortality
Azotemia
Hydralazine
Angiotensin Type 1 Receptor
Albuminuria
Blood Pressure
Kidney
Fibrosis
Angiotensinogen
Reperfusion Injury
Nephrectomy
Drinking Water
Atrophy
Up-Regulation
Control Groups
Genes

ASJC Scopus subject areas

  • General

Cite this

Cheng, S. Y., Chou, Y. H., Liao, F. L., Lin, C. C., Chang, F-C., Liu, C. H., ... Lin, S. L. (2016). Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury. Scientific Reports, 6, [34265]. https://doi.org/10.1038/srep34265

Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury. / Cheng, Shun Yang; Chou, Yu Hsiang; Liao, Fang Ling; Lin, Chun Chi; Chang, Fan-Chi; Liu, Chia Hao; Huang, Tao Min; Lai, Chun Fu; Lin, Yu Feng; Wu, Vin Cent; Chu, Tzong Shinn; Wu, Ming Shiou; Lin, Shuei Liong.

In: Scientific Reports, Vol. 6, 34265, 28.09.2016.

Research output: Contribution to journalArticle

Cheng, SY, Chou, YH, Liao, FL, Lin, CC, Chang, F-C, Liu, CH, Huang, TM, Lai, CF, Lin, YF, Wu, VC, Chu, TS, Wu, MS & Lin, SL 2016, 'Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury', Scientific Reports, vol. 6, 34265. https://doi.org/10.1038/srep34265
Cheng, Shun Yang ; Chou, Yu Hsiang ; Liao, Fang Ling ; Lin, Chun Chi ; Chang, Fan-Chi ; Liu, Chia Hao ; Huang, Tao Min ; Lai, Chun Fu ; Lin, Yu Feng ; Wu, Vin Cent ; Chu, Tzong Shinn ; Wu, Ming Shiou ; Lin, Shuei Liong. / Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury. In: Scientific Reports. 2016 ; Vol. 6.
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