Chronic kidney disease induced in mice by reversible unilateral ureteral obstruction is dependent on genetic background.
Chronic kidney disease (CKD) begins with renal injury; the progression thereafter depends upon a number of factors, including genetic background. Unilateral ureteral obstruction (UUO) is a well-described model of renal fibrosis and as such is considered a model of CKD. We used an improved reversible unilateral ureteral obstruction (rUUO) model in mice to study the strain dependence of development of CKD after obstruction-mediated injury. C57BL/6 mice developed CKD after reversal of three or more days of ureteral obstruction as assessed by blood urea nitrogen (BUN) measurements (>40 mg/dl). In contrast, BALB/c mice were resistant to CKD with up to 10 days ureteral obstruction. During rUUO, C57BL/6 mice exhibited pronounced inflammatory and intrinsic proliferative cellular responses, disruption of renal architecture, and ultimately fibrosis. By comparison, BALB/c mice had more controlled and measured extrinsic and intrinsic responses to injury with a return to normal within several weeks after release of ureteral obstruction. Our findings provide a model that allows investigation of the genetic basis of events during recovery from injury that contribute to the development of CKD.
Puri
Tipu S
TS
Section of Nephrology, Department of Medicine, University of Chicago, 5841 South Maryland Ave., Chicago, IL 60637, USA. tpuri@medicine.bsd.uchicago.edu
Shakaib
Mohammed I
MI
Chang
Anthony
A
Mathew
Liby
L
Olayinka
Oladunni
O
Minto
Andrew W M
AW
Sarav
Menaka
M
Hack
Bradley K
BK
Quigg
Richard J
RJ
D000818:Animals; D020022:Genetic Predisposition to Disease; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014517:Ureteral Obstruction / Q000150:complications*