Correlates of Renal Atrophy in Murine 2 Kidney 1 Clip Hypertension

Abstract

Renal artery stenosis (RAS) is a common disorder associated with both cardiovascular and renal morbidity and mortality. Recent studies have shown that stenting of the stenotic kidney fails to improve renal or cardiovascular outcomes, prompting a search for more effective therapies. Strain‐specific variability in renal outcomes is a well recognized problem associated with murine models of chronic injury. The objective of this study was to define strain specific differences in renal outcome and correlation with parameters of injury in a murine model of RAS.We used a 0.25 mm polytetrafluoroethylene cuff to establish RAS in mice (n=292 total). We examined the correlation between age, time following surgery, body weight, blood pressure, heart and kidney weights, ratio of STK/CLK weight, and plasma angiotensin level in 3 murine strains. Percent atrophy in the STK as a function of time following RAS surgery is summarized in the table below: Strain 1 Week 2 Week 4 Week 6 Week 129 21% 31% XX 45% C57BLKS/J 25% 51% 63% 72% C57BL/6J XX XX 39% 41% The right kidney weight and the STK/CLK weight ratio correlated with %atrophy in all strains, with the strongest correlation observed in C57BL/6J mice. In C57BL/6J mice, blood pressure correlated with %atrophy. CLK weight correlated with heart weight, with the strongest correlation observed in 129Sv mice. In BLKS mice, the time following surgery and age correlated with CLK weight and %atrophy in the STK; blood pressure correlated with plasma angiotensin level.We conclude that RAS produces severe chronic renal injury in the STK of all strains studied, with the most severe injury observed in C57BLKS/J mice.The STK/CLK weight ratio correlated most strongly with %atrophy and can be used to predict development of chronic renal damage in all strains. Hypertrophy of the CLK, as measured by CLK weight, strongly correlated with heart weight.