Plasma and urine renalase levels and activity during the recovery of renal function in kidney transplant recipients

Abstract

Renalase is a recently described enzyme secreted by the kidney into both plasma and urine, where it was suggested to degrade catecholamines contributing to blood pressure control. While there is a controversy regarding the relationship between renal function and plasma renalase levels, there is virtually no data in humans on plasma renalase activity as well as on both urine renalase levels and activity. We prospectively examined the time course of plasma and urine renalase levels and activity in 26 end-stage renal disease (ESRD) patients receiving a cadaver kidney transplant (cadaver kidney recipients [CKR]) before surgery and during the recovery of renal function up to day 90 post transplant. The relationship with sympathetic and renal dopaminergic activities was also evaluated. The recovery of renal function in CKR closely predicted decreases in plasma renalase levels (r = 0.88; P < 0.0001), urine renalase levels (r = 0.75; P < 0.0001) and urine renalase activity (r = 0.56; P < 0.03), but did not predict changes in plasma renalase activity (r = -0.02; NS). Plasma norepinephrine levels positively correlated with plasma renalase levels (r = 0.64, P < 0.002) as well as with urine renalase levels and activity (r = 0.47 P < 0.02; r = 0.71, P < 0.0005, respectively) and negatively correlated with plasma renalase activity (r = -0.57, P < 0.002). By contrast, plasma epinephrine levels positively correlated with plasma renalase activity (r = 0.67, P < 0.0001) and negatively correlated with plasma renalase levels (r = -0.62, P < 0.003). A significant negative relationship was observed between urine dopamine output and urine renalase levels (r = -0.48; P < 0.03) but not with urine renalase activity (r = -0.33, NS). We conclude that plasma and urine renalase levels closely depend on renal function and sympathetic nervous system activity. It is suggested that epinephrine-mediated activation of circulating renalase may occur in renal transplant recipients with good recovery of renal function. The increase in plasma renalase activity observed in ESRD patients and renal transplant recipients can be explained on the basis of reduced inhibition of the circulating enzyme.

Effect of Salt Intake and Potassium Supplementation on Urinary Renalase and Serum Dopamine Levels in Chinese Adults

“…To date, there are very few studies that have examined the association between urine renalase and dopamine. Based on a human model of end-stage renal disease, it was documented that the significant negative relationship was observed between urinary renalase levels and urine dopamine output [26]. In addition, the increases in urinary renalase levels and activity during high-sodium intake, observed in both 3/4nx and sham rats, were accompanied by 2-fold sodium-induced increases in daily urinary dopamine output in both groups of rats [9].…”

“…Quelhas-Santos et al [26] reported that urine renalase levels and activities were markedly increased in end-stage renal disease patients. A recent article by Rybi-Szuminska et al [27] delivered the first evidence for reference values of urine renalase excretion in a healthy pediatric population, with the highest levels in the youngest children.…”

Renalase — a new marker or just a bystander in cardiovascular disease: clinical and experimental data

“…A Portuguese group observed also that circulating renalase levels in a group of patients with end stage renal disease, as in transplant recipients, were higher compared to healthy donors. They used, as did Malyszko et al [29], a commercially available ELISA kit to measure renalase levels [31]. Genetic studies conducted by Stec et al [16] delivered new information about SNPs in the renalase gene among haemodialysed patients with hypertension.…”

“…Moreover, renalase activity measurements need further explanation. Different study groups [1,31] measured renalase activity with the use of kits designed for measuring MOA activity. The measurement of renalase activity was extrapolated from the reaction based on the detection of H 2 O 2 in a horseradish peroxidase-coupled reaction.…”

Renalase Secreted by Human Kidney HEK293T Cells Lacks its N-Terminal Peptide: Implications for Putative Mechanisms of Renalase Action

“…Another study demonstrated that plasma renalase levels were lower in hypertensive patients after surgical repair of coarctation of aorta (n= 50) than in controls (n=50) [10]. Monitoring of plasma and urine renalase levels in 26 patients with end stage renal disease (ESRD) before and after transplantation of cadaver kidneys revealed gradual normalization of increased renalase levels both in blood and urine [11]. All these data point to a clear need for better understanding of structural and functional characteristics of this protein.…”