TY - JOUR
T1 - A systematic review and meta-analysis of murine models of uremic cardiomyopathy
AU - Soppert, Josefin
AU - Frisch, Janina
AU - Wirth, Julia
AU - Hemmers, Christian
AU - Boor, Peter
AU - Kramann, Rafael
AU - Vondenhoff, Sonja
AU - Moellmann, Julia
AU - Lehrke, Michael
AU - Hohl, Mathias
AU - van der Vorst, Emiel P C
AU - Werner, Christian
AU - Speer, Thimoteus
AU - Maack, Christoph
AU - Marx, Nikolaus
AU - Jankowski, Joachim
AU - Roma, Leticia Prates
AU - Noels, Heidi
N1 - Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
PY - 2022/2
Y1 - 2022/2
N2 - Chronic kidney disease (CKD) triggers the risk of developing uremic cardiomyopathy as characterized by cardiac hypertrophy, fibrosis and functional impairment. Traditionally, animal studies are used to reveal the underlying pathological mechanism, although variable CKD models, mouse strains and readouts may reveal diverse results. Here, we systematically reviewed 88 studies and performed meta-analyses of 52 to support finding suitable animal models for future experimental studies on pathological kidney-heart crosstalk during uremic cardiomyopathy. We compared different mouse strains and the direct effect of CKD on cardiac hypertrophy, fibrosis and cardiac function in "single hit" strategies as well as cardiac effects of kidney injury combined with additional cardiovascular risk factors in "multifactorial hit" strategies. In C57BL/6 mice, CKD was associated with a mild increase in cardiac hypertrophy and fibrosis and marginal systolic dysfunction. Studies revealed high variability in results, especially regarding hypertrophy and systolic function. Cardiac hypertrophy in CKD was more consistently observed in 129/Sv mice, which express two instead of one renin gene and more consistently develop increased blood pressure upon CKD induction. Overall, "multifactorial hit" models more consistently induced cardiac hypertrophy and fibrosis compared to "single hit" kidney injury models. Thus, genetic factors and additional cardiovascular risk factors can "prime" for susceptibility to organ damage, with increased blood pressure, cardiac hypertrophy and early cardiac fibrosis more consistently observed in 129/Sv compared to C57BL/6 strains.
AB - Chronic kidney disease (CKD) triggers the risk of developing uremic cardiomyopathy as characterized by cardiac hypertrophy, fibrosis and functional impairment. Traditionally, animal studies are used to reveal the underlying pathological mechanism, although variable CKD models, mouse strains and readouts may reveal diverse results. Here, we systematically reviewed 88 studies and performed meta-analyses of 52 to support finding suitable animal models for future experimental studies on pathological kidney-heart crosstalk during uremic cardiomyopathy. We compared different mouse strains and the direct effect of CKD on cardiac hypertrophy, fibrosis and cardiac function in "single hit" strategies as well as cardiac effects of kidney injury combined with additional cardiovascular risk factors in "multifactorial hit" strategies. In C57BL/6 mice, CKD was associated with a mild increase in cardiac hypertrophy and fibrosis and marginal systolic dysfunction. Studies revealed high variability in results, especially regarding hypertrophy and systolic function. Cardiac hypertrophy in CKD was more consistently observed in 129/Sv mice, which express two instead of one renin gene and more consistently develop increased blood pressure upon CKD induction. Overall, "multifactorial hit" models more consistently induced cardiac hypertrophy and fibrosis compared to "single hit" kidney injury models. Thus, genetic factors and additional cardiovascular risk factors can "prime" for susceptibility to organ damage, with increased blood pressure, cardiac hypertrophy and early cardiac fibrosis more consistently observed in 129/Sv compared to C57BL/6 strains.
KW - CARDIAC DYSFUNCTION
KW - CHRONIC KIDNEY-DISEASE
KW - GELATINASE-ASSOCIATED LIPOCALIN
KW - HEART-FAILURE
KW - INFLAMMATION
KW - LEFT-VENTRICULAR HYPERTROPHY
KW - MICE
KW - MYOCARDIAL-INFARCTION
KW - OXIDATIVE STRESS
KW - RENAL DYSFUNCTION
KW - cardiac dysfunction
KW - cardiovascular disease
KW - chronic kidney disease
KW - fibrosis
KW - hypertrophy
KW - uremic cardiomyopathy
U2 - 10.1016/j.kint.2021.10.025
DO - 10.1016/j.kint.2021.10.025
M3 - (Systematic) Review article
C2 - 34774555
SN - 0085-2538
VL - 101
SP - 256
EP - 273
JO - Kidney International
JF - Kidney International
IS - 2
ER -