title: Angiotensin II overcomes strain-dependent resistance of rapid CKD progression in a new remnant kidney mouse model.
abstract: The remnant kidney model in C57BL/6 mice does not develop progressive chronic kidney disease (CKD). In this study we modified the model to mimic features of human CKD and to define accelerants of disease progression using three strains of mice. Following the procedure, there was a progressive increase in albuminuria, progressive loss in renal function, severe glomerulosclerosis and interstitial fibrosis, hypertension, cardiac fibrosis, and anemia by 4 weeks in CD-1 mice and by 12 weeks in 129S3 mice. In contrast, even after 16 weeks, the C57BL/6 mice with a remnant kidney had modestly increased albuminuria without increased blood pressure and without developing CKD or cardiac fibrosis. The baseline blood pressure, determined by radiotelemetry in conscious animals, correlated with CKD progression rates in each strain. Administering angiotensin II overcame the resistance of C57BL/6 mice to CKD following renal mass reduction, displaying high blood pressure and albuminuria, severe glomerulosclerosis, and loss of renal function by 4 weeks. Decreasing blood pressure with olmesartan, but not hydralazine, in CD-1 mice with a remnant kidney reduced CKD progression and cardiac fibrosis. C57BL/6 mice with a remnant kidney and DOCA-salt hypertension developed modest CKD. Each strain had similar degrees of interstitial fibrosis in three different normotensive models of renal fibrosis. Thus, reducing renal mass in CD-1 or 129S3 mice mimics many features of human CKD. Angiotensin II can convert the C57BL/6 strain from CKD resistant to susceptible in this disease model.
authors.affiliation: Renal Diagnostics and Therapeutics Unit, Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1268, USA.
authors.forename: Asada
authors.initials: A
authors.lastname: Leelahavanichkul
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.forename: Xuzhen
authors.initials: X
authors.lastname: Hu
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisner
authors.forename: Yuning
authors.initials: Y
authors.lastname: Huang
authors.forename: Richard
authors.initials: R
authors.lastname: Chen
authors.forename: Diane
authors.initials: D
authors.lastname: Mizel
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schnermann
authors.forename: Peter S T
authors.initials: PS
authors.lastname: Yuen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000503:physiopathology; D000740:Anemia / Q000209:etiology / Q000503:physiopathology; D000804:Angiotensin II / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D002908:Chronic Disease; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000209:etiology / Q000503:physiopathology; D006331:Heart Diseases / Q000209:etiology / Q000503:physiopathology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D015918:Infusion Pumps, Implantable; D055104:Infusions, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009392:Nephrectomy; D017673:Sodium Chloride, Dietary; D013045:Species Specificity; D013686:Telemetry; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D000804:Angiotensin II; D006830:Hydralazine; D003900:Desoxycorticosterone; C437965:olmesartan