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 ≈3-fold lower (P<0.05), whereas glomerulosclerosis was ≈6-fold higher (P<0.05) 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 ≈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.
authors.affiliation: From the Research and Development Service, Edward Hines Jr. VA Hospital, Hines, IL (A.J.P.); Department of Medicine, (A.J.P.) and Department of Pathology (M.P.), Loyola University-Chicago, Maywood, IL; and Department of Electrical and Computer Engineering, Illinois Institute of Technology, Chicago (J.L., G.A.W.).
authors.forename: Maria
authors.initials: M
authors.lastname: Picken
authors.affiliation: From the Research and Development Service, Edward Hines Jr. VA Hospital, Hines, IL (A.J.P.); Department of Medicine, (A.J.P.) and Department of Pathology (M.P.), Loyola University-Chicago, Maywood, IL; and Department of Electrical and Computer Engineering, Illinois Institute of Technology, Chicago (J.L., G.A.W.).
authors.forename: Jianrui
authors.initials: J
authors.lastname: Long
authors.affiliation: From the Research and Development Service, Edward Hines Jr. VA Hospital, Hines, IL (A.J.P.); Department of Medicine, (A.J.P.) and Department of Pathology (M.P.), Loyola University-Chicago, Maywood, IL; and Department of Electrical and Computer Engineering, Illinois Institute of Technology, Chicago (J.L., G.A.W.).
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Williamson
authors.affiliation: From the Research and Development Service, Edward Hines Jr. VA Hospital, Hines, IL (A.J.P.); Department of Medicine, (A.J.P.) and Department of Pathology (M.P.), Loyola University-Chicago, Maywood, IL; and Department of Electrical and Computer Engineering, Illinois Institute of Technology, Chicago (J.L., G.A.W.). aaron.polichnowski@va.gov.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Polichnowski
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis / Q000473:pathology; D005919:Glomerular Filtration Rate / Q000502:physiology; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology* / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D009395:Nephritis, Interstitial / Q000473:pathology* / Q000503:physiopathology; D011507:Proteinuria / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D018570:Risk Assessment; D018709:Statistics, Nonparametric
keywords: fibrosis; glomerular filtration rate; glomerulosclerosis, focal segmental; hypertension; ischemia renal circulation