Renocardiac syndromes: physiopathology and treatment stratagems

Abstract

Purpose of review: Bidirectional inter-organ interactions are essential for normal functioning of the human body; however, they may also promote adverse conditions in remote organs. This review provides a narrative summary of the epidemiology, physiopathological mechanisms and clinical management of patients with combined renal and cardiac disease (recently classified as type 3 and 4 cardiorenal syndrome). Findings are also discussed within the context of basic research in animal models with similar comorbidities.

Sources of information: Pertinent published articles were identified by literature search of PubMed, MEDLINE and Google Scholar. Additional data from studies in the author's laboratory were also consulted.

Findings: The prevalence of renocardiac syndrome throughout the world is increasing in part due to an aging population and to other risk factors including hypertension, diabetes and dyslipidemia. Pathogenesis of this disorder involves multiple bidirectional interactions between the kidneys and heart; however, participation of other organs cannot be excluded. Our own work supports the hypothesis that the uremic milieu, caused by kidney dysfunction, produces major alterations in vasoregulatory control particularly at the level of the microvasculature that results in impaired oxygen delivery and blood perfusion.

Limitations: Recent clinical literature is replete with articles discussing the necessity to clearly define or characterize what constitutes cardiorenal syndrome in order to improve clinical management of affected patients. Patients are treated after onset of symptoms with limited available information regarding etiology. While understanding of mechanisms involved in pathogenesis of inter-organ crosstalk remains a challenging objective, basic research data remains limited partly because of the lack of animal models.

Implications: Preservation of microvascular integrity may be the most critical factor to limit progression of multi-organ disorders including renocardiac syndrome. More fundamental studies are needed to help elucidate physiopathological mechanisms and for development of treatments to improve clinical outcomes.

Fig. 1

Schematic of pathways for kidney injury leading to heart and multi-organ failure

Fig. 2

Change in LV oxygen transport versus hematocrit (Hct) for control dogs (n = 5, open circle) at baseline, dobutamine-5 (5 μg/Kg/min; open triangle) and dobutamine-10 (10 μg/Kg/min; open square). Stage 1 CKD (n = 5, closed symbols and stage 2 CKD (n = 5, open dotted symbols) are shown. In control dogs, LV oxygen transport increased in direct relation to intravenous dobutamine levels. In dogs with Stage 1 or 2 CKD, maximal LV oxygen transport was achieved at the lower dose of intravenous dobutamine compared to controls. Data shown are means ± 1SD