Key result
In Ren-2 transgenic rats, combined CKD and CHF significantly worsened survival compared to single organ disease, with females exhibiting poorer survival than males in the combined disease model.
In a hypertensive rat model, combined CKD and CHF worsens long-term mortality compared to single organ disease, with notable sex differences where females have poorer survival in the combined disease state.
The role of hypertension and the renin-angiotensin system (RAS) in sex-related differences in the course of chronic kidney disease (CKD) and congestive heart failure (CHF) remain unclear, especially when the two diseases are combined. In male and female Ren-2 transgenic rats (TGR), a model of hypertension with activation of endogenous RAS, CKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of an aorto-caval fistula (ACF). The primary aim of the study was to examine long-term CKD- and CHF-related mortality, especially in animals with CKD and CHF combined, with particular interest in the potential sex-related differences. The follow-up period was 23 weeks after the first intervention (5/6 NX). We found, first, that TGR did not exhibit sexual dimorphism in the course of 5/6 NX-induced CKD. Second, in contrast, TGR exhibited important sex-related differences in the course of ACF-induced CHF-related mortality: intact female TGR showed higher survival rate than male TGR. This situation is reversed in the course of combined 5/6 NX-induced CKD and ACF-induced CHF-related mortality: intact female TGR exhibited poorer survival than male TGR. Third, the survival rate in animals with combined 5/6 NX-induced CKD and ACF-induced CHF was significantly worsened as compared with rat groups that were exposed to 'single organ disease'. Collectively, our present results clearly show that CKD aggravates long-term mortality of animals with CHF. In addition, TGR exhibit remarkable sexual dimorphism with respect to CKD- and CHF-related mortality, especially in animals with combined CKD and CHF.
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Červenka et al. (2016) studied Chronic kidney disease and congestive heart failure. Combined 5/6 nephrectomy-induced CKD and aorto-caval fistula-induced CHF vs. Single organ disease (CKD alone or CHF alone) and male vs female was evaluated on Long-term CKD- and CHF-related mortality. In Ren-2 transgenic rats, combined CKD and CHF significantly worsened survival compared to single organ disease, with females exhibiting poorer survival than males in the combined disease model.
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