Renalase, kidney and cardiovascular disease: Are they related or just coincidentally associated?

Abstract

Cardiovascular diseases, including hypertension are the leading cause of death in the developed countries. Diabetes and chronic kidney disease became also more prevalent reaching almost the level of epidemy. Researchers are looking eagerly for the new risk and/or pathogenetic factors, as well as therapeutic option in these disease. It has been suggested that human kidney releases a protein named renalase into the bloodstream. It is supposed to be an enzyme which breaks down catecholamines in the blood circulation and regulate blood pressure. However, there were several doubts whether renalase exerts monoaminooxidase activity, or if it is monoaminooxidase at all. Recently, a hypothesis that it is also a cytokine was postulated. Studies on renalase polymorphisms in hypertension, cardiovascular disease or diabetes are inconsistent. Similarly, there are several discrepancies in the animal on the possible role of renalase in hypertension and cardiovascular diseases. Some studies report a protective role of renalase in acute kidney injury, whereas others showed that renalase levels were mainly dependent on kidney function, indicating rather a role of kidney in excretion of this substance. Moreover, validated assays are needed to evaluate renalase levels and activity. On one hand a deeper and more accurate link between renalase and cardiovascular diseases require further profound research, on the other hand whether or not renalase protein could be a new therapeutic target in these pathologies should also be considered. Whether renalase, discovered in 2005, might be a Holy Grail of hypertension, linking kidney and cardiovascular diseases, remains to be proven.

Introduction

Hypertension is one of common cardiovascular diseases and also a major risk factor of atherosclerosis, and plays crucial roles in the occurrence and development of coronary heart diseases (CHD) [1]. It has been shown that the amplitude of the increase in blood pressure is linearly correlated with the incidence of CHD [2]. On the other hand, kidney disease and blood pressure are inevitably linked. In addition, chronic kidney disease (CKD) is associated with a high risk of cardiovascular disease (CVD) [3]. Hypertension is present in approximately 80–85% of patients with CKD [4]. The prevalence of hypertension increases together with GFR decline [4]. The etiology of high blood pressure is multifactorial in this population and one or more of risk factors may play a role in an individual patient, while in essential hypertension genetic predisposition is considered [4]. One or more of the following factors may contribute to the hypertension in patients with chronic kidney disease: sodium retention, increased activity of the renin–angiotensin system, enhanced activity of the sympathetic nervous system, secondary hyperparathyroidism, use of erythropoiesis stimulating agents [4]. However, the pathogenesis of hypertension is still the matter of extensive research.