Preclinical Cardiorenal Interrelationships in Essential Hypertension

Abstract

A diseased heart causes numerous adverse effects on kidney function, and vice versa renal disease can significantly impair cardiac function. Beyond these heart-kidney interrelationships at the clinical level, a reciprocal association has been suggested to exist even in the early stages of those organs' dysfunction. The aim of the present review is to provide evidence of the presence of a preclinical cardiorenal syndrome in the particular setting of essential hypertension, focusing on the subsequent hypertensive sequelae on heart and kidneys. In particular, a plethora of studies have demonstrated not only the predictive role of kidney damage, as expressed by either decreased glomerular filtration or increased urine albumin excretion, for adverse left ventricular functional and structural adaptations but also preclinical heart disease, i.e. left ventricular hypertrophy that is associated with deterioration of renal function. Notably, these reciprocal interactions seem to exist even at the level of microcirculation, since both coronary flow reserve and renal hemodynamics are strongly related with clinical and preclinical renal and cardiac damage, respectively. In this preclinical setting, common pathophysiological denominators, including the increased hemodynamic load, sympathetic and renin-angiotensin system overactivity, increased subclinical inflammatory reaction, and endothelial dysfunction, account not only for the reported associations between overt cardiac and renal damage but also for the parallel changes that occur in coronary and renal microcirculation.

Salt loading exacerbates diastolic dysfunction and cardiac remodeling in young female Ren2 rats

“…It is clear from other rodent models that salt-induced LV remodeling impairs LV relaxation and diastolic function through increases in fibrosis and cardiac stiffness [41–43]. In this regard, alterations in the composition of collagen isoforms within the myocardial extracellular matrix can determine the extent of ventricular stiffness and impaired relaxation.…”

Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

“…In humans, subclinical cardiac damage is manifested in left ventricular hypertrophy (LVH), as determined by the left ventricular mass index (125 g/m 2 for men and 110 g/m 2 for women) [10] , while subclinical renal damage is manifested in decreased levels of estimated glomerular filtration rate (eGFR), increased levels of albuminuria, and increased levels of serum Cr [10] . LVH is considered a predictor of adverse renal outcome in patients with high cardiovascular risk [24] .…”

“…A new concept called 'preclinical CRS' has recently been introduced. Based on this concept, hypertension in elderly patients acts as a risk factor for subclinical cardiac and renal damage and predisposes these patients to developing CRS type 1 and 3 when they are exposed to contrast media [10] .…”

“…In this review, we discuss how the aging male SHR can be a suitable animal model for the evaluation of the interaction between CI-AKI and CRS type 1 and 3. Table 1 and figure 1 show similar risk factors for CI-AKI, including hypertension, obesity, and age, shared by the SHR [17][18][19][20][21][22][23] and humans with preclinical CRS [10,18,[23][24][25][26][27][28][29] . In humans with preclinical CRS, essential hypertension acts as a risk factor for subclinical cardiac and renal damage.…”

“…In humans with preclinical CRS, essential hypertension acts as a risk factor for subclinical cardiac and renal damage. Hypertension precedes overt cardiac and renal dysfunction [10] and accounts for 25% of all causes of chronic kidney disease (CKD) [18] . The SHR is a reliable model of a naturally developing pressure load akin to essential hypertension in humans; therefore, it is generally accepted that the SHR represents an analogue of human essential hypertension [17,30] .…”