Update on the Classification and Pathophysiological Mechanisms of Pediatric Cardiorenal Syndromes

Abstract

Cardiorenal syndrome (CRS) is defined as a disorder resulting from the abnormal interaction between the heart and kidney, in which acute or chronic dysfunction of one organ may lead to acute and/or chronic dysfunction of the other. The functional interplay between the heart and kidney is characterized by a complex bidirectional symbiotic interaction, regulated by a wide array of both genetic and environmental mechanisms. There are at least five known subtypes of CRS, based on the severity of clinical features and the degree of heart/renal failure. The fourth subtype (cardiorenal syndrome type 4 (CRS4)) is characterized by a primary chronic kidney disease (CKD), which in turn leads to a decreased cardiac function. Impairment of renal function is among the most important pathophysiological factors contributing to heart failure (HF) in the pediatric age group, and cardiovascular complications could be one of the most important causes of mortality in pediatric patients with advanced CKD. In this context, a loss of glomerular filtration rate directly correlates with both the progression of cardiovascular complications in CRS and the risk of HF. This review describes the interaction pathways between the heart and kidney and the recently identified pathophysiological mechanisms underlying pediatric CRS, with a special focus on CRS4, which encompasses both primary CKD and cardiovascular disease (CVD).

The Function and Role of the Cilium in the Development of Ciliopathies

“…Other manifestations are congenital fibrocystic diseases of the liver and pancreas, skeletal dysplasias diabetes, obesity, and consequential complications to other organs including the heart. 42 43 44 45…”

“…Other manifestations are congenital fibrocystic diseases of the liver and pancreas, skeletal dysplasias diabetes, obesity, and consequential complications to other organs including the heart. [42][43][44][45] JBTS is a ciliopathy with extensive genetic heterogeneity and also with an extensive phenotypic manifestation. It is an autosomal-recessive disorder, described for the first time in 1969 in a family containing four siblings and during the neonatal period characterized by defects in the cerebellum (cerebellar vermis aplasia) and the eye (coloboma), and also as retinitis pigmentosa, congenital hypotonia, and either ocular motor apraxia or irregularities in breathing patterns.…”

Alström's Syndrome: Neurological Manifestations and Genetics

“…[30][31][32] Several pathomechanisms have been identified, and genetic and nongenetic factors may induce the risk of several childhood diseases as part of a complex multifactorial pathophysiology. [33][34][35][36] Studies of human genetic variation using genome (or exome) sequencing led to the identification of several different genes 37,38 increasing our understanding of many rare and neglected pediatric diseases, 21,39,40 and this highlighted the importance of omic sciences in defining the clinical spectrum and the therapies tailored to many neurological and metabolic disorders of infancy. 41 Next-generation sequencing technologies as well as fine comparative genomic hybridization studies should always be employed in the molecular diagnostic workup of patients clinically suspected with ALMS, to rule out any other underlying clinical condition or genetic defect.…”

New Insight in Cardiorenal Syndrome: From Biomarkers to Therapy

“…However, the prevalence, risk factors and prognosis of pediatric CRS is less characterized. An extensive description of pediatric CRS has been recently reviewed elsewhere [ 13 ]. In this review article, we will discuss the current knowledge on the pathophysiology of CRS in adults, as well as the utility of biomarkers in cardiac and kidney dysfunction and potential insights into novel therapeutics for the management of CRS patients.…”