Progression of Chronic Kidney Disease After Acute Kidney Injury: Role of Self-Perpetuating Versus Hemodynamic-Induced Fibrosis Journal Article

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Authors: Picken, M; Long, J; Williamson, G. A.; Polichnowski, A. J.
Article Title: Progression of Chronic Kidney Disease After Acute Kidney Injury: Role of Self-Perpetuating Versus Hemodynamic-Induced Fibrosis
Abstract: The relative contribution of self-perpetuating versus hemodynamic-induced fibrosis to the progression of chronic kidney disease (CKD) after acute kidney injury (AKI) is unclear. In the present study, male Sprague-Dawley rats underwent right uninephrectomy and were instrumented with a blood pressure radiotelemeter. Two weeks later, separate groups of rats were subjected to 40 minutes renal ischemia-reperfusion or sham surgery and followed up for 4 or 16 weeks to determine the extent to which glomerulosclerosis and tubulointerstitial fibrosis as a result of the AKI-CKD transition (ie, at 4 weeks post AKI) change over time during the progression of CKD (ie, at 16 weeks post AKI). On average, tubulointerstitial fibrosis was approximately 3-fold lower (P0.05), whereas glomerulosclerosis was approximately 6-fold higher (P0.05) at 16 versus 4 weeks post AKI. At 16 weeks post AKI, marked tubulointerstitial fibrosis was only observed in rats exhibiting marked glomerulosclerosis, proteinuria, and kidney hypertrophy consistent with a hemodynamic pathogenesis of renal injury. Moreover, quantitative analysis between blood pressure and renal injury revealed a clear and modest blood pressure threshold (average 16-week systolic blood pressure of approximately 127 mm Hg) for the development of glomerulosclerosis. In summary, modest levels of blood pressure may be playing a substantial role in the progression of renal disease after AKI in settings of preexisting CKD associated with 50% loss of renal mass. In contrast, these data do not support a major role of self-perpetuating tubulointerstitial fibrosis in the progression CKD after AKI in such settings.
Journal Title: Hypertension (Dallas, Tex.: 1979)
Volume: 68
Issue: 4
ISSN: 1524-4563; 0194-911X
Publisher: American Heart Association, Inc  
Journal Place: United States
Date Published: 2016
Start Page: 921
End Page: 928
Language: ENG
DOI/URL:

10.1161/HYPERTENSIONAHA.116.07749
Notes: LR: 20161025; CI: (c) 2016; GR: IK2 BX001285/BX/BLRD VA/United States; GR: VA999999/Intramural VA/United States; JID: 7906255; VAPA805464; OID: NLM: PMC5016243 [Available on 10/01/17]; OID: NLM: VAPA805464 [Available on 10/01/17]; OTO: NOTNLM; PMCR: 2017/10/01; 2016/04/24 [received]; 2016/07/22 [accepted]; ppublish