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Introduction and objectives Prevalence of hypertension increases as glomerular filtration rate (GFR) declines. Renalase metabolizes catecholamines and have an important role in blood pressure (BP) regulation. The purpose of the study was to evaluate the effect of kidney transplantation on renalase levels and BP in kidney donors and recipients. Materials and methods Twenty kidney transplant recipients and their donors were included in the study. Serum renalase levels and ambulatory BP values were measured in both donors and recipients before and after transplantation. Factor associated with change in renalase and BP levels were also evaluated. Results In donors; mean GFR and hemoglobin levels decreased while night-time systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels and serum renalase levels increased simultaneously after nephrectomy. Day-time SBP and DBP levels did not changed and the night/day ratio of mean arterial pressure (MAP) increased significantly. In recipients, mean GFR increased, while mean serum renalase levels, creatinine and BP levels decreased after transplantation. Correlation analysis revealed that changes in MAP correlated with alteration in serum renalase levels and GFR. Conclusions After transplantation, serum renalase levels increased in donors and decreased in recipients. The renalase levels are associated with change in MAP and circadian rhythm of BP in donors and recipients.

Preeclampsia (PE) is one of the major contributors to maternal and fetal mortality worldwide. Many host-related biomolecules regulate the pathophysiology of PE. The current study aims to examine the role of the renalase in PE manifestations. A total of 384 Chinese women consisting of subjects with normotensive pregnancy (n = 105), women with PE (n = 121), and healthy women (n = 158) were included in the study. Serum renalase level was measured in all subjects by ELISA. Renalase gene polymorphisms (rs10887800, rs2576178, and rs2296545) were genotyped by PCR-RFLP. The pregnant women had elevated renalase levels compared to healthy controls and subjects with PE. Renalase level was negatively correlated with systolic and diastolic blood pressure. Interestingly, renalase was positively correlated with the glomerular filtration rate. Prevalence of homozygous mutant (GG) and minor allele (G) for rs10887800 and rs2576178 renalase gene polymorphisms were significantly higher in PE patients compared to normotensive pregnant women and healthy controls. Furthermore, an association of G-G-C haplotype with susceptibility to PE was also noticed. A low level of renalase may be associated with an increased risk of PE during pregnancy. Renalase gene polymorphisms (rs10887800 and rs2576178) are correlated with serum renalase and are associated with predisposition to PE development in the Chinese cohort.

IntroductionExercise training is beneficial for reducing obesity. In particular, exercise training can lower the catecholamine concentration in circulation. Renalase, whose expression was first confirmed in the kidneys, is a physiologically active substance that decomposes circulating catecholamines; additionally, it has been reported to be present in the skeletal muscles. The aim of this study was to clarify the expression of renalase in the skeletal muscles and kidneys after high-intensity exercise training in obese mice.Material and methodsThe mice were divided into four groups: normal diet and sedentary, normal diet and exercise training, high-fat diet and sedentary, and high-fat diet and exercise training, and the test was performed for 8 weeks.ResultsBody weight and skeletal muscle wet weight were reduced by high-fat diet intake but were rescued by training. Skeletal muscle renalase gene expression was significantly increased by exercise training. However, in the kidneys the gene expression of renalase was significantly increased by high-fat diet intake and exercise training. No significant changes were observed in the gene expression of catecholamine-degrading enzymes, catechol-O-methyltransferase and monoamine oxidase A and B.ConclusionWe demonstrated that exercise training increased the gene expression of renalase in the skeletal muscles and kidneys, thus lowering circulating catecholamine levels. This may lead to amelioration of obesity as catecholamines are lipolytic.

Aims Renalase (RNLS) is an enzyme with monoamine oxidase activity that metabolizes circulating catecholamines. The RNLS gene Asp37Glu missense polymorphism (rs2296545) has been associated with hypertension, cardiac hypertrophy and dysfunction, and stroke. The purpose of our study was to investigate the potential involvement of this polymorphism in the microvascular complications of type 2 diabetes (T2DM). Methods In this case–control study, the polymorphism was genotyped in 860 patients with T2DM and 400 healthy controls. The genotype and allele distribution was compared in subgroups of patients: with diabetic nephropathy (DN+) (n = 405) versus DN− (independently of the presence of DR) and, similarly, patients with diabetic retinopathy (DR+) (n = 328) versus DR− (independently of the presence of DN). Results No significant association was detected between analyzed polymorphism and DN. In contrast, the retinopathy subgroup showed a significantly higher frequency of G allele (OR 1.4, 95% CI 1.16–1.72, p = 0.0005) and GG genotype (OR 1.86, 95% CI 1.26–2.75, p = 0.001) than DR− patients. The effect of RNLS Glu37Asp polymorphism on DR remained significant after adjustments for age, gender, BMI, and duration of T2DM (p = 0.005). Conclusions This is the first study to investigate RNLS gene polymorphism in microvascular complications of T2DM. The results suggest that RNLS rs2296545 SNP might be considered a risk factor for diabetic retinopathy in T2DM patients. This can provide new insight into the role of renalase gene in the pathophysiology of microvascular complications of diabetes.

Background: Biomarkers of left atrial (LA) overload are considered factors affecting the efficacy of atrial fibrillation (AF) treatment. Increasing obesity rates contribute to a growing number of obese patients qualified for electrical cardioversion (CVE).Biomarkers of left atrial (LA) overload are considered as factors influencing efficacy of atrial fibrillation (AF) treatment. The increasing rate of obesity contributes to obese patients constituting a significant group of subjects qualified to electrical cardioversion (CVE). Aims: The aim of the study was to evaluate serum concentrations of biomarkers of LA overload and their impact on the efficacy of CVE. Methods: A total of 82 patients with persistent AF who underwent successful CVE were prospectively enrolled in the study. The study population was divided into the obese group (OG) and the nonobese group (NOG). The serum levels of the following biomarkers were measured on the day of admission and at follow‑up: high‑sensitivity C‑reactive protein (hs‑CRP), N‑terminal pro‑B‑type natriuretic peptide, copeptin, galectin 3, growth differentiation factor 15 (GDF‑15), and renalase. Results: Baseline and follow‑up hs‑CRP levels were increased in the OG compared with the NOG. Four‑week CVE efficacy was 38.8% in the OG and 60.6% in the NOG. Time of the observation, allocation to the groups, and CVE outcomes showed no associations with most LA biomarkers during follow‑up. Baseline concentrations of 2 biomarkers of LA overload were associated with clinical characteristics of the study group, that is, log10 serum GDF‑15 and log10 serum renalase levels correlated positively with the CHA2DS2‑VASc score. Conclusions: Although obesity modifies the long‑term efficacy of CVE, the OG and NOG did not differ significantly in most biomarkers of LA overload, except hs‑CRP. The efficacy of CVE seems to be independent of the levels of biomarkers. A favorable procedure outcome did not affect their blood concentrations.

Purpose An increased risk of cardiovascular mortality and morbidity has been linked with metabolic syndrome (MetS), described as the secondary risk reduction target. These patients are predisposed to high complication levels such as unstable angina-pectoris (USAP) by MetS. As with the role of renalase in the regulation of blood pressure (BP), the study was carried out to determine the levels of renalase circulation in patients with USAP and MetS (USAP+MetS), as well as the association of renalase gene (RNLS) rs10887800 polymorphism and USAP and MetS susceptibility. Patients and Methods A total of 134 patients with USAP+MetS and 134 control subjects were recruited in this case-control study. Results Renalase was found to have a significantly higher level in USAP+MetS patients (23.28 ± 4.09 µg/dL) than in healthy ones (20.81 ± 2.73 µg/dL) (P < 0.001). Also, it was shown that renalase sensitivity and specificity values for the early diagnosis of USAP and MetS seemed to be 53.7% and 76.9, respectively. Moreover, the value for renalase area under curve (AUC) was 0.654 (95% CI: 0.58-0.72). The frequency of rs10887800 AG and GG genotypes of RNLS gene was significantly higher in USAP+MetS patients than in control subjects, suggesting that this genotype might be a risk factor against USAP+MetS (OR = 2.114 [95% CI 1.113-4.016]; P = 0.022) and (OR = 2.057 [95% CI 1.011-4.186]; P = 0.047), respectively. Conclusion The present results showed that renalase serum levels increased in USAP and MetS patients. Moreover, the RNLS rs10887800 was reported to be associated with a higher risk of USAP+MetS.

Renalase is a recently identified flavoprotein oxidase, secreted mainly by the kidneys, which takes part in the degradation of catecholamines. The catecholamine inactivating effect results in the modulation of the sympathetic system tension and, consequently, in a decrease of blood pressure, myocardial contractility, heart rate, and vascular tone. Besides its enzymatic capacity, renalase shows cytoprotective properties by activating mitogen-activated protein kinase (MAPK) pathway. Several single nucleotide polymorphisms (SNPs) of the renalase gene have been identified, of which the most widely studied in relation to the development of selected diseases are rs2296545, rs10887800, and rs2576178. Numerous publications prove the contribution of renalase to the occurrence of cardiovascular diseases, kidney diseases, ischaemic stroke, diabetes type 1 and 2, as well as female infertility and schizophrenia. Further extended research into the various mechanisms of renalase activity may result in the use of this oxidase or its analogues as a therapeutic and/or diagnostic tool.

Background Renalase plays an important role in blood pressure regulation. Obstructive sleep apnea (OSA) is a common respiratory disorder associated with hypertension and cardiovascular complications. The aim of the study was to assess the relationship between sleep apnea and renalase concentration. Material and methods Adult patients (n = 113) were evaluated for OSA in a sleep laboratory using polysomnography. The respiratory events were scored according to the standards developed by the American Academy of Sleep Medicine. The blood renalase concentration was determined by the ELISA (enzyme-linked immunosorbent assay) test. Results OSA (AHI ≥ 5) was diagnosed in 71% (n = 80) of the studied population. Renalase concentration was statistically significantly lower in the group with moderate-to-severe OSA (AHI ≥ 15) compared with the group without OSA (AHI p = 0.042). We have found statistically significant negative correlation between renalase and AHI in hypertensives, but not in normotensives. The statistically significant negative correlation was observed between AHI and renalase in the whole studied group, in males, and in the group of age 60 years old. Based on the regression model, it was shown that lower renalase concentration, hypertension, higher BMI, and male gender are independently associated with higher AHI. Conclusions There is a relationship between the blood renalase concentration and the severity of OSA, which may influence hypertension development in OSA.

Renalase is predominantly expressed in the kidney, where it plays a role in catecholamine metabolism and blood pressure regulation. Moderate‐intensity exercise (MEX) has been shown to increase the concentration of renalase in the blood and to reduce renal function in humans. Moreover, such exercise was also reported to increase catecholamine levels. Here, we examined renalase concentration in the blood and renalase expression levels in different organs after MEX in rats. Twelve male Wistar rats were made to run on a treadmill (MEX group) for 60 min at 20 m·min−1, after resting for 15 min. The control group rats were euthanized after resting on the treadmill. Tissue and blood samples were analyzed using western blotting, real‐time RT‐PCR and ELISA. Overall, the concentrations of renalase in the blood were significantly higher in the MEX group than that in the control group. Renalase expression was decreased in the kidney after 60 min of exercise, whereas the expression of renalase mRNA and protein in the extensor digitorum longus and plantaris muscles, respectively, increased after exercise. However, the expression of renalase in the other tissues examined did not change after acute exercise. In conclusion, we report that MEX for 60 min increases both renalase concentration in the blood and its expression in skeletal muscle., The concentration of renalase in the blood and its expression in skeletal muscle were significantly increased in rats that underwent moderate‐intensity exercise as compared with the sedentary group, whereas renalase expression in the kidney decreased after exercise. Renalase expression in other tissues did not change after acute exercise.

Renalase is a novel enzyme that can regulate blood pressure by degrading circulating catecholamines. We aimed to evaluate the possible effect of rs2296545, rs2576178 and rs10887800 polymorphisms of the

Background: Renalase is an enzyme and a cytokine involved in cell survival. Since its discovery, associations between it and both cardiovascular and kidney disease have been noted. Recognizing this, we conducted a study in which we followed patients with chronic kidney disease. Material and methods: The study involved 90 CKD patients with varying stages of the disease and 30 healthy controls. Renalase was measured with an ELISA kit, and patients were followed-up after a median of 18 months. During the follow-up, we asked about the occurrence of MACE, all-cause mortality and the need for dialysis initiation. Results: In CKD subgroups, RNSL correlated with all-cause death only in the HD group (Rs = 0.49, p &lt, 0.01). In the whole CKD population, we found a positive correlation of RNSL concentration and both MACE occurrence (Rs = 0.38, p &lt, 0.001) and all-cause death (Rs = 0.34, p &lt, 0.005). There was a significant increase in MACE occurrence probability in patients with elevated renalase levels (&gt, 25 μg/mL). Conclusions: Elevated renalase levels can be used as a risk factor of MACE in patients with CKD, but its long-term utility needs further research. High renalase levels are a risk factor of death among CKD patients. In HD patients, all deaths were observed among patients with &gt, 30 μg/mL, this level could be used as a “red flag” marker in future studies.

Aim: Introduction: Lupus nephritis (LN) is a substantial risk factor for death and morbidity in patients with Systemic Lupus Erythematosus (SLE) (SLE). Despite excellent immunosuppressive therapy, it nevertheless leads to a disproportionate percentage of persons developing chronic kidney disease (CKD) or end-stage renal disease (ESRD). Renalase is a distinctive cytokine-like protein generated by the kidneys that promote cell survival. It has been recently linked to the etiology of LN and may be an ideal candidate as a sensitive biomarker for flare-ups and LN remission. Aim of the work: The purpose of this study was to evaluate the utility of human serum renalase as a biomarker for assessing disease activity and severity in SLE, as well as to evaluate if it can be used as a sensitive biomarker in this capacity. Methods: This study consists of around 23 healthy controls and 46 individuals with LN. These participants were separated into two equal groups according to disease activity as determined by the SLEDAI (SLE Disease Activity Index): 23 cases with LN who had disease activity and 23 cases who did not. The concentration of human serum Renalase (RNLS) was evaluated using a very sensitive commercial enzyme immunoassay that captures renalase from serum using (RNLS) antibody. Results: Renalase concentrations were significantly greater in LN cases than in healthy controls (P-value

Heart failure represents a growing health problem, with increasing morbidity and mortality globally. According to the mechanisms involved in the pathogenesis of heart failure, many biomarkers have been proposed for the timely diagnosis and prognostication of patients with heart failure, but other than natriuretic peptides, none of them has gained enough clinical significance. Renalase, a new protein derived from kidneys was demonstrated to metabolize catecholamines and to have a cardioprotective role. The aim of the study was to determine whether renalase and brain natriuretic peptide (BNP) concentration could be used to differentiate heart failure patients stratified to the category of the ejection fraction and whether plasma renalase could be used as a biomarker for left ventricle hypertrophy in all subgroups of heart failure patients. We included patients diagnosed with heart failure and stratified them to the three subgroups according to the ejection fraction. Regarding echocardiographic parameters, HFmrEF had an intermediate profile in between HFrEF and HFpEF, with statistical significance in most evaluated parameters. BNP concentration was significantly different in all three subgroups (p<0.001), and renalase was statistically higher in HFrEF (p=0.007) compared to the HFmrEF and HFpEF, where its results were similar, without statistical significance. Renalase plasma concentration was demonstrated to be highly and positively associated with left ventricle mass index in HFrEF (p=0.029), as well as increased plasma concentration of BNP (p=0.006). In the HFmrEF group of patients, body mass index was positively associated with LVMI (p=0.05), while in the patients with HFpEF, diabetes mellitus was demonstrated to have a positive association with LVMI (p=0.043). These findings suggest that renalase concentration may be measured in order to differentiate patients with reduced ejection fraction. Plasma renalase concentrations positively correlated with left ventricle hypertrophy in patients with reduced ejection fraction, being strongly associated with increased left ventricular mass index.

Background/Aims: Patients with chronic kidney disease (CKD) have been found to show markedly increased rates of end-stage renal disease, major adverse car diovascular and cerebrovascular events (MACCEs), and mortality. Therefore, new biomarkers are required for the early detection of such clinical outcomes in pa tients with CKD. We aimed to determine whether the level of circulating renalase was associated with CKD progression, MACCEs, and all-cause mortality, using data from a prospective randomized controlled study, Kremezin STudy Against Renal disease progression in Korea (K-STAR; NCT 00860431). Methods: A retrospective analysis of the K-STAR data was performed including 383 patients with CKD (mean age, 56.4 years; male/female, 252/131). We measured circulating renalase levels and examined the effects of these levels on clinical outcomes. Results: The mean level of serum renalase was 75.8 ± 34.8 μg/mL. In the multi variable analysis, lower hemoglobin levels, higher serum creatinine levels, and diabetes mellitus were significantly associated with a higher renalase levels. Over the course of a mean follow-up period of 56 months, 25 deaths and 61 MACCEs occurred. Among 322 patients in whom these outcomes were assessed, 137 adverse renal outcomes occurred after a mean follow-up period of 27.8 months. Each 10- μg/mL increase in serum renalase was associated with significantly greater haz ards of all-cause mortality and adverse renal outcomes (hazard ratio [HR] = 1.112, p = 0.049; HR = 1.052, p = 0.045). However, serum renalase level was not associated with the rate of MACCEs in patients with CKD. Conclusions: Our results indicated that circulating renalase might be a predictor of mortality and adverse renal outcomes in patients with CKD.

Schizophrenia, particularly the form related to excessive dopamine (DA), is a chronic psychotic disorder affecting millions of people worldwide. Renalase metabolizes its catecholamine (CA) substrates, including DA, suggesting that there might be an association between renalase levels and schizophrenia occurrence. Therefore, the current study aimed to evaluate the renalase and CA levels in the serum of patients with schizophrenia.The study was conducted with thirty-three schizophrenia patients and an age- and gender-matched group of thirty-one controls. Renalase and CA levels were measured by using an enzyme-linked immunosorbent assay (ELISA).Renalase levels were significantly lower in the schizophrenia patients than in the control group (The high DA levels in patients with schizophrenia might be due to low renalase levels. Renalase enzyme levels may play a substantial role in the pathophysiology of schizophrenia. Thus, this enzyme might be a new future target for the treatment and diagnosis of schizophrenia after intrabrain renalase and DA dynamics have been further evaluated.Shizofrenija, posebno oblik sa povećanim dopaminom (DA) je hronični psihijatrijski poremećaj od koga boluju milioni ljudi širom sveta. Relanaza metaboliše supstrate kateholamine (CA), uključujući DA, što ukazuje da može da postoji veza između nivoa relanaze i pojave shizofrenije. Shodno ovome, ovo izučavanje je imalo za cilj da proceni nivoe relanaze i CA u serumu pacijenata sa shizofrenijom.Izučavanje je obuhvatilo trideset tri pacijenta sa shizofrenijom i trideset jednu osobu iste starosti i pola kao kontrolnu grupu. Nivoi renalaze i CA mereni su primenom ELISA metode.Nivoi renalaze bili su značajno niži kod pacijenaza sa shizofrenijom nego u kontrolnoj grupi (p0,05), dok su nivoi DA bili značajno viši (p0,05). Nivoi epinefrina (Epi) u obe grupe bili su manji (p=0,186), dok su nivoi norepinfrina u pacijenata sa shizofrenijom bili značajno niži nego u kontrolnoj grupi (p0,05). Površina ispod krive za renelaze-dopamin i renelaze-epinefrin odnose bili su 0,805, 95% konfidens interval CI: 0,594–0,859 (p=0,032); i 0,656, 95% CI: 0,520–0,791 (p=002).Visoki nivoi DA u pacijenata sa shizofrenijom mogu biti usled niskih nivoa renalaze. Nivoi renalaze enzima mogu imati značajnu ulogu u patofiziologiji shizofrenije. To znači da ovaj enzima može imati značajnu ulogu u tretmanu i dijagnostikovanju shizofrenije te ona treba dalje da bude izučavana kao i dinamika DA.

Background Renalase (RNL) is a controversial enzyme as to whether it oxidizes catecholamines (CAs) (as is generally accepted) in the blood or not. CAs (dopamine [DPMN], epinephrine [EPI] and norepinephrine [NEPI]) are associated with hypertension, including pregnancy-induced hypertension, which occurs in 8–10% of all pregnancies. Therefore, the aim of the study was to compare CAs and renalase concentration in (i) normotensive controls (C), (ii) patients with preeclampsia (PE) and (iii) patients with severe preeclampsia (SPE), which is one of the well-known symptoms of hypertension. Methods This case-control study involved 90 women divided into three groups – 30 C, 30 PE and 30 SPE – whose age and body mass indexes (BMIs) were similar. A total of 270 blood samples (90 maternal samples, 90 umbilical cord artery samples and 90 umbilical cord vein samples) were obtained. CAs and RNL concentrations of the biological samples were measured by enzyme-linked immunosorbent assay (ELISA). Results Comparing the amounts of CAs, RNL and systolic blood pressure (SBP)/diastolic blood pressure (DBP) between healthy control pregnant women and pregnant women with PE and SPE (SBP/DBP was 120/80 mm Hg for C, above 140/90 mm Hg for PE and above 160/110 mm Hg for SPE), the levels of CAs were significantly increased whereas RNL was reduced. The correlation between SBP/DBP and the amount of RNL in pregnant women with PE and SPE was negative. Conclusions These novel results are evidence that hypertension seen in PE and SPE is directly related to increased levels of CAs and reduced RNL concentrations. The use of RNL preparations may be preferred in future to prevent maternal and perinatal morbidity and mortality due to pregnancy-induced hypertension.

The aim is to explore the treatment effect of coronary artery disease (CAD) and hypertension on plasma levels of renalase activity and also the possible association of renalase rs10887800 gene polymorphism with CAD and hypertension. A total of 286 patients who received coronary angiography were included in the study. Subjects were divided into four groups including (1) hypertensive with no CAD (H-Tens, n = 60); (2) CAD with hypertension (CAD + H-Tens, n = 71); (3) CAD with no hypertension (CAD, n = 61); and (4) nonhypertensive with no CAD as a control group (Con, n = 69). The plasma renalase activity was measured using the Amplex Red Monoamine Oxidase Assay Kit. Renalase rs10887800 single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Atorvastatin (P = 0.005), losartan (P 0.001), and captopril (P = 0.001) were administered significantly more in case groups compared with the Con group. Significant higher and lower levels of renalase activity were observed in H-Tens and CAD patients compared with control subjects (P 0.001 for both comparisons). Furthermore, no significant differences were obtained in the risk or protective effects of renalase rs10887800 SNP against hypertension and/or CAD in both recessive and dominant genetic models (P 0.05). According to the findings of the present study, atorvastatin and losartan therapy assumes considerable significance in alleviating hypertension, but not CAD, by increasing the renalase activity. Furthermore, it was found that renalase rs10887800 is less likely a predisposing factor for susceptibility to hypertension and/or CAD in an Iranian southeast population.

Aim: To evaluate serum renalase and salivary alpha amylase concentrations and their relationship with plasma catecholamine levels in patients with Metabolic Syndrome (MS), Type 2 Diabetes Mellitus (T2DM), and End-Stage Renal Disease (ESRD). Method: In cross-sectional study 163 patients were enrolled; 43 patients with MS, 93 withT2DM, 13 with ESRD, and 14 healthy subjects (control group). All patients had their ascription to the UMAA/UMF No. 75, in Morelia, Michoacan, Mexico. Glucose, creatinine, cholesterol, triglycerides, HDL, and renalase were measurement in serum, and Dopamine (DA), Epinephrine (E) and Norepinephrine (NE) in plasma. An aliquot of saliva was collected for alpha amylase determination. Results: High plasma concentrations of DA, E and NE (p

Background Diabetes mellitus (DM) and chronic kidney disease (CKD) are common causes of morbidity and mortality. Flaxseed contains several bioactive compounds that have been shown to possess anti-inflammatory and antioxidative properties. The aim of the present study was to investigate the possible effect of flaxseed in diabetic rats with adenine–induced CKD. Methods Male Wister rats (n = 48) were randomly divided into seven equal groups and treated for 33 consecutive days as follows: G1: control. G2 adenine, G3: streptozotocin (STZ), G4: flaxseed, G5: adenine+flaxseed, G6: STZ+flaxseed, G7: adenine+STZ+flaxseed). DM or CKD were experimentally induced by a single intraperitoneal injection of streptozotocin (STZ) or by adenine via oral gavage, respectively. Results Rats fed adenine alone exhibited several changes including decreased body weight, increased food and water intake and urine output, increased urinary albumin/creatinine ratio. They also showed an increase in plasma urea and, creatinine, indoxyl sulfate, neutrophil gelatinase-associated lipocalin and cystatin C, and a decrease in renalase activity. These were associated with significant changes in inflammatory and oxidative biomarkers, e.g., increase in 8-isoprostane, 8 -hydroxy -2-deoxy guanosine and decrease in antioxidant enzymes, as well as increase in interleukins 1β and 6, and NF-κB, and a decrease in interlukin-10. Histopathologically, there was increased tubular necrosis and fibrosis. Concomitant administration of adenine and STZ further worsened the renal damage induced by adenine alone. Flaxseed significantly ameliorated the changes caused by adenine and STZ, given either singly or in combination. Conclusion These findings suggest that flaxseed is a potential therapeutic agent in attenuating the progression of CKD in diabetes.

Background: Renalase has been implicated in chronic heart failure (CHF); however, nothing is known about renalase discriminatory ability and prognostic evaluation. The aims of the study were to assess whether plasma renalase may be validated as a predictor of ischemia in CHF patients stratified to the left ventricular ejection fraction (LVEF) and to determine its discriminatory ability coupled with biomarkers representing a range of heart failure (HF) pathophysiology: brain natriuretic peptide (BNP), soluble suppressor of tumorigenicity (sST2), galectin-3, growth differentiation factor 15 (GDF-15), syndecan-1, and cystatin C.Methods: A total of 77 CHF patients were stratified according to the LVEF and were subjected to exercise stress testing. Receiver operating characteristic curves were constructed, and the areas under curves (AUC) were determined, whereas the calibration was evaluated using the Hosmer-Lemeshow statistic. A DeLong test was performed to compare the AUCs of biomarkers.Results: Independent predictors for ischemia in the total HF cohort were increased plasma concentrations: BNP (p = 0.008), renalase (p = 0.012), sST2 (p = 0.020), galectin-3 (p = 0.018), GDF-15 (p = 0.034), and syndecan-1 (p = 0.024), whereas after adjustments, only BNP (p = 0.010) demonstrated predictive power. In patients with LVEF p = 0.001), renalase (p < 0.001), sST2 (p = 0.004), galectin-3 (p = 0.003), GDF-15 (p = 0.001), and syndecan-1 (p < 0.001). The AUC of BNP (0.837) was statistically higher compared to those of sST2 (DeLong test: p = 0.042), syndecan-1 (DeLong: p = 0.022), and cystatin C (DeLong: p = 0.022). The AUCs of renalase (0.753), galectin-3 (0.726), and GDF-15 (0.735) were similar and were non-inferior compared to BNP, regarding ischemia prediction. In HFrEF patients, the AUC of BNP (0.980) was statistically higher compared to those of renalase (DeLong: p < 0.001), sST2 (DeLong: p < 0.004), galectin-3 (DeLong: p < 0.001), GDF-15 (DeLong: p = 0.001), syndecan-1 (DeLong: p = 0.009), and cystatin C (DeLong: p = 0.001). The AUC of renalase (0.814) was statistically higher compared to those of galectin-3 (DeLong: p = 0.014) and GDF-15 (DeLong: p = 0.046) and similar to that of sST2. No significant results were obtained in the patients with LVEF >45%.Conclusion: Plasma renalase concentration provided significant discrimination for the prediction of ischemia in patients with CHF and appeared to have similar discriminatory potential to that of BNP. Although further confirmatory studies are warranted, renalase seems to be a relevant biomarker for ischemia prediction, implying its potential contribution to ischemia-risk stratification.

Summary Introduction Kidneys are the most frequently injured organ in the genitourinary system, but there is no specific biological marker for this trauma. Renalase may be a descriptive biomarker of the pathology that causes renal ischemia, nephrotoxicity, and acute renal failure. Objective This study investigated the role of serum and urine levels of renalase for the diagnosis of renal injury in rats with experimentally induced blunt renal trauma. Study design Thirty 3-month-old Sprague–Dawley adult male rats were divided into five groups (n = 6) as follows: control (Group 1), sham (Group 2), right nephrectomy (Group 3), left renal trauma (Group 4), and right nephrectomy plus left renal trauma (Group 5). Serum samples were acquired 3, 24 and 48 h post-trauma, and urine samples were acquired between 0–24 and 24–48 h post-trauma. Changes in serum and urine levels of renalase, dopamine, epinephrine, metanephrine, normetanephrine, urea, and creatinine were assessed after blunt renal trauma. Results No significant changes in serum levels of these compounds were observed at 3 h post-trauma in Groups 1 and 2 or in urine collected sequentially at 0–24 and 24–48 h. By contrast, levels of renalase, dopamine, metanephrine, and normetanephrine in serum increased during hour 3 in Groups 4 and 5. Moreover, increases in urine levels of renalase, dopamine, epinephrine, metanephrine, and normetanephrine were observed at hours 0–24 in Groups 4 and 5. Discussion A definitive diagnosis of traumatic renal injury in children is made with contrast-enhanced computed tomography. However, the scan results in high doses of radiation exposure to children. Here, we report for the first time that renalase levels may be useful as a biomarker for the diagnosis of renal injury due to blunt renal trauma. Conclusion Renalase may be a simple, effective, and noninvasive biomarker that indicates traumatic renal injury. It could be used as an adjunct for evaluation, particularly for isolated traumatic renal injury in cases where access to computed tomography is not straightforward. Download : Download high-res image (507KB) Download : Download full-size image Summary Figure . Renalase levels in a) serum (3, 24, and 48 h) and b) urine (0–24 and 24–48 h).

Chronic kidney disease (CKD) is an inflammatory disease leading to kidney insufficiency and uremia. Renalase is a novel flavoprotein with enzymatic activities. Previous studies have shown that chronic kidney disease may influence renalase serum levels. Renalase metabolises catecholamines and therefore may be involved in the pathogenesis of hypertension and other diseases of the circulatory system. In this study, we examined renalase levels in serum, erythrocytes and urine from haemodialysis CKD patients. The study enrolled 77 haemodialysis CKD patients and 30 healthy subjects with normal kidney function as the control group. Renalase serum and urine concentrations in CKD patients were significantly increased when compared with control subjects (185.5 ± 64.3 vs. 19.6 ± 5.0 ng/mL, p &lt, 0.00001 and 207.1 ± 60.5 vs. 141.6 ± 41.3 ng/mL, p = 0.00040, respectively). In contrast, renalase levels in erythrocytes were significantly lower in CKD patients when compared with control subjects (176.5 ± 60.9 vs. 233.2 ± 83.1 ng/mL, p = 0.00096). Plasma levels of dopamine, adrenaline and noradrenaline were also significantly lower in CKD patients when compared with controls. Conclusions: Increased serum and urine concentrations of renalase in haemodialysis CKD patients are likely related to compensatory production in extrarenal organs as a result of changes in the cardiovascular system and hypertension. The decreased plasma concentrations of catecholamines may be due to their increased degradation by plasma renalase. Decreased renalase levels in erythrocytes may be probably due to lower renalase synthesis by the kidneys in CKD. The results indicate the presence of renalase in erythrocytes.

Chronic kidney disease (CKD) is an independent risk factor for adverse cardiovascular and cerebrovascular events (MACCEs), and mortality since the earlier stages. Therefore, it is critical to identify the link between CKD and cardiovascular risk (CVR) through early and reliable biomarkers. Acknowledging that CKD and CKD progression are associated with increased sympathetic tone, which is implicated in CVR, and that renalase metabolizes catecholamines, we aimed to evaluate the relationship between renalase serum levels (RNLS) and cardiovascular and renal outcomes. The study included 40 pre-dialysis CKD patients (19F:21M) with median age of 61 (IQ 45–66) years. At baseline, we measured RNLS as well as routine biomarkers of renal and cardiovascular risk. A prospective analysis was performed to determine whether RNLS are associated with CKD progression, MACCEs, hospitalizations and all-cause mortality. At baseline, the median level of RNLS and median estimated glomerular filtration rate (eGFR) were 63.5 (IQ 48.4–82.7) µg/mL and 47 (IQ 13–119) mL/min/1.73 m2, respectively. In univariate analysis, RNLS were strongly associated with eGFR, age and Charlson Index. Over the course of a mean follow-up of 65 (47 to 70) months, 3 (7.5%) deaths, 2 (5%) fatal MACCEs, 17 (42.5%) hospital admissions occurred, and 16 (40%) patients experienced CKD progression. In univariate analysis, RNLS were associated with CKD progression (p = 0.001), hospitalizations (p = 0.001) and all-cause mortality (p = 0.022) but not with MACCEs (p = 0.094). In adjusted analysis, RNLS predicted CKD progression and hospitalizations regardless of age, Charlson comorbidity index, cardiovascular disease, hypertension, diabetes and dyslipidemia. Our results suggest that RNLS, closely related with renal function, might have a potential role as predictor of renal outcomes, hospitalizations, and mortality in pre-dialysis CKD patients.

Renalase is a renal tubule–secreted especially in the proximal tubule, flavin adenine dinucleotide–dependent amine oxidase that degrades catecholamines including epinephrine, norepinephrine and dopamine without effects against other physiologic amines including serotonin, tyramine, or spermidine. Renalase is secreted in blood and its levels are regulated by three key factors: renal function, renal perfusion and catecholamine levels, they hold a direct relationship with the glomerular filtration rate and kidney mass.Renal sympathetic nerve activation may negatively modulate kidney and plasma renalase levels where increased renal sympathetic nerve activity during and after renal IR exacerbates ischemic AKI by increasing plasma catecholamine levels and downregulating kidney/plasma renalase levels. Renalase decreases cardiac output and BP by regulating plasma catecholamine levels, modulates the severity of renal ischemia and reperfusion injury, and also serves as a novel and sensitive biomarker for the early detection of ischemic AKI. Recombinant renalase therapy may provide a novel therapeutic tool for the prevention and treatment of AKI.

Denervation‐induced muscle atrophy increases signaling through both protein degradation and synthesis pathways. Renalase is a flavin adenine dinucleotide‐dependent amine oxidase that inhibits apoptosis and inflammation and promotes cell survival. This study aimed to elucidate the effect of renalase on denervation‐induced muscle atrophy. We used 7‐week‐old renalase knock‐out (KO) mice (a model of denervation‐induced muscle atrophy) and wild‐type (WT) mice (KO: n = 6, weight = 20–26 g; WT: n = 5, weight = 19–23 g). After their left legs were denervated, these mice were killed 1 week later. KO mice had lighter muscle weight than the WT mice. We observed an increase in molecular signaling through protein degradation pathway as well as oxidative stress in denervated muscles compared with that in sham‐operated muscles in both WT and KO mice. Additionally, we also observed the main effect of renalase in WT and KO mice. Mitochondrial oxidative phosphorylation protein content was lower in denervated muscles than in sham‐operated muscles in both WT and KO mice. However, a significant difference was noted in the reaction with Akt and p70S6K (components of the protein synthesis pathway) between WT and KO mice. In conclusion, mice with renalase deficiency demonstrated an attenuation of denervation‐induced muscle atrophy. This might be related to catecholamines because signaling through the protein synthesis pathway was increased following denervation in renalase KO mice compared with that in WT mice, despite showing no change in signaling through protein degradation pathways., We show that signaling through the protein synthesis pathway in the denervated limb of renalase knock‐out mice was increased compared with wild‐type mice, despite no change in signaling through protein degradation pathways.

IntroductionRenalase (RNLS), a novel secreted plasma flavoprotein, has anti-inflammatory effects in a variety of disease processes. Severe COVID-19 disease is associated with disordered inflammatory responses. We hypothesized that reduced plasma RNLS levels could be a marker of COVID-19 disease severity.MethodsPlasma was collected from 51 hospitalized COVID-19 patients and 15 uninfected non-hospitalized controls. Plasma RNLS and cytokine levels were measured and sociodemographic and clinical data were collected from chart review. Data were analyzed using nonparametric analyses and Kaplan Meir curve log rank analysis.ResultsPlasma RNLs levels were negatively correlated with inflammatory markers, including IL-1β, IL-6, and TNFα (p = 0.04, p = 0.03, p = 0.01, respectively). Patients with COVID-19 disease had lower levels of RNLS than controls. Lower levels of RNLS were associated with more severe disease among COVID-19 patients. Low RNLS was also associated with worse survival among COVID-19 patients (HR = 4.54; 95% CI: 1.06-19.43; p = 0.005).ConclusionLow plasma RNLS levels are associated with severe COVID-19 disease and may be a useful additional biomarker when identifying patients with severe COVID-19 disease. Given RNLS’ antiinflammatory properties and negative correlation with inflammatory markers, these findings also suggest evidence of a potential pathophysiological mechanism for severe COVID-19 disease.

Renalase, a novel flavoprotein that is mainly expressed in the kidney and heart, plays a crucial role in hypertension. Recent studies have shown that renalase is expressed at low levels in the serum of patients with heart failure, while the role of renalase and its mechanism in cardiac failure is unclear. Adult Sprague-Dawley (SD) rats were used to investigate the role and function of renalase in the pathological process of transverse aortic constriction (TAC)-induced heart failure. Renalase-human protein chip analysis showed that renalase was directly associated with P38 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling. We further used lentivirus-mediated RNA interference to study the role of renalase in the progression of pathological ventricular hypertrophy and found that renalase inhibition attenuated the noradrenaline-induced hypertrophic response in vitro or the pressure overload-induced hypertrophic response in vivo. Recombinant renalase protein significantly alleviated pressure overload-induced cardiac failure and was associated with P38 and ERK1/2 signaling. These findings demonstrate that renalase is a potential biomarker of hypertrophy and that exogenous recombinant renalase is a potential and novel drug for heart failure.

Urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and renalase were recently studied for their potential role in the early detection of acute kidney injury (AKI) in patients with cirrhosis. Our study was conducted on 50 patients with end-stage liver disease undergoing living donor liver transplantation. The patients were divided into two groups: Group I contained 23 patients with AKI who had undergone liver transplantation and Group II included 27 non-AKI patients who had undergone liver transplantation. Serum renalase and NGAL levels were measured by ELISA; renalase was measured on day 1, day 7, and three months after liver transplantation. NGAL was measured on day 1 postliver transplantation. There was an improvement in liver function, kidney functions, hemoglobin level, platelet count, and C- reactive protein levels in patients at three months posttransplantation when compared to day 1, day 3, and day 7 (P < 0.01). Comparison of the renalase level at day 1, day 7, and three months showed that there was a highly significant decline at three months in the AKI group compared to the non-AKI group (P < 0.01). Regarding the NGAL level at day 1, there was no significant difference between the AKI and non-AKI groups (P > 0.05). The receiver operating characteristic curve for the renalase biomarker showed a borderline significant change between the AKI and non-AKI groups at day 1 [area under the curve (AUC): 0.54, P = 0.08], day 7 (AUC: 0.605, P = 0.08), and three months (AUC: 0.605, P = 0.08). However, the NGAL biomarker level was not significantly different between the AKI and non-AKI groups. Our study suggests that renalase showed a better predictive value and a higher accuracy in identifying postliver transplantation patients with AKI than NGAL.

Objective: Heart failure (HF) represents a huge socio-economic burden. It has been demonstrated, experimentally, that renalase, a newly discovered protein, prevents cardiac hypertrophy and adverse ...

Background Renalase is a flavoprotein that plays a protective role in chronic kidney disease (CKD) and cardiovascular diseases. The secretion and way of action of this protein are still discussed. The aim of our study was to estimate the balance between serum and urine renalase in healthy individuals and CKD patients, using two parameters: fractional excretion (FE) and serum-to-urine renalase ratio (StURR). Methods Our study involved 28 healthy volunteers and 62 patients with CKD in stages I to IV. The concentration of renalase in serum and urine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (EIAab, Wuhan, China). We analyzed associations between renalase levels in urine and serum, and other parameters: sex, age, GFR, presence of hypertension, diabetes, and proteinuria, and determined the serum-to-urine renalase ratio and fractional excretion of renalase. Results Renalase and serum-to-urine ratio were significantly higher in CKD patients in comparison with the control group. Fractional excretion was lower in CKD patients but this difference did not reach the statistical significance (p = 0.092). Multivariate analysis performed in the CKD group showed, that from mentioned parameters, serum renalase was the only significant independent factor strongly positively associated with urinary renalase concentration. Conclusions The serum-to-urine ratio is significantly and about 6.5-fold higher in CKD patients, and the fractional excretion of renalase is 3-fold, but not significantly lower in CKD patients. Renalase levels in both serum and urine are not related to the glomerular filtration rate and not associated with blood pressure.

It would be of great clinical value to find an indicator that can accurately evaluate the early-stage renal injury in primary hypertension. Previous findings have shown renalase not only plays an important role in hypertension but also closely correlates with kidney function. The purpose of this study is to investigate whether urinary renalase could be used as a predictive index of early-stage renal damage in patients with primary hypertension. Urinary albumin to creatinine ratio (UACR) was used to divide subjects with primary hypertension into two groups: a no renal damage (NRD) group (UACR 30 mg/g). Subjects with normal examination results were randomly included in a healthy control (HC) group. Urinary renalase was determined through an enzyme-linked immunosorbent assay (ELISA). Urinary renalase continued to reduce among the HC (n = 81), NRD (n = 84) and RD group (n = 80), while systolic blood pressure (SBP) increased. Urinary renalase was negatively correlated with SBP in all the groups. Among the subjects with stage 1 primary hypertension, urinary renalase in the RD group was lower than the NRD group, while the UACR was higher, and urinary renalase was negatively correlated with the UACR. A multiple linear stepwise regression analysis showed that there was a linear regression relationship between the increase of the UACR and urinary renalase, heart rate (HR), SBP and serum creatinine. In addition, the standardized partial regression coefficient of urinary renalase was the highest. The performance of urinary renalase as a marker for the diagnosis of early-stage renal damage in patients with primary hypertension was 0.968 with a cut off value of 2.01 µg/ml. Taken together, urinary renalase was further decreased in patients with early-stage renal damage and primary hypertension, and consequently, it could be used as a predictive index. Impact statement In patients with early-stage kidney damage of primary hypertension, there are no obvious structural or functional changes, which leads to a high level of diagnostic omissions. Therefore, it would be of great clinical value to find an indicator that can accurately evaluate the early-stage renal injury in primary hypertension. Urinary albumin to creatinine ratio (UACR) is a classic indicator used in early-stage renal damage, but it is affected by many factors. Renalase, a protein discovered by Xu in 2005, not only plays an important role in hypertension but also closely correlates with kidney function. In our study, we found that urinary renalase was further decreased in patients with early-stage renal damage in primary hypertension, and it could be used as a predictive index. This finding could help to diagnose the early-stage renal damage in primary hypertension much earlier and improve the prognosis of these patients.

Aim: To compare the blood renalase and cerebellin-1 levels of acute central serous chorioretinopathy (CSC) patients with healthy subjects. Method: A total of 33 eyes withacutenaïve CSC (less than 2 months duration)and 31 healthy subjects were enrolled in this study. Idiopathic CSC was diagnosed based on the presence of a serous detachment of the neurosensory retina involving the macula that was confirmed using optical coherence tomography and leakage at the retinal pigment epithelium level using fluorescein angiography. Blood samples were collected and centrifuged at 4000 g for 10 minutes. The serum samples were collected and stored at -80 °C until required for analysis. Serum renalase and cerebellin-1 levels were measured using an ELISA kit. Results: In CSC group 11 patients were female and 22 patients were male. In control group 10 participants were female and 20 were male. The sex was similar between groups. Mean age in CSC group was 41, 04±5, 94, in control group was 40, 67±6, 53. Mean ages were similar between groups. Mean renalase levels in CSC group was 27, 19±14, 01 ng/ml and in control group was 19, 12±15, 57 ng/mL. Mean renalase level was higher in CSC group. Mean cerebellin levels were 57, 76±29, 72 pg/mL and 52, 50±29, 25 pg/mL in CSC and in control groups, respectively. Mean cerebellin levels were similar in groups. Conclusion: Comparing with healthy subjects serum renalase levels were higher and cerebellin-1 levels were similar in CSC patients.

Objective: Large solitary renal cysts (SRC) may result in renal ischemia. Renalase, a protective enzyme against ischemic renal injury, has an effective role in controlling blood pressure (BP). Therefore, we aimed to investigate the relationships among pre- and postoperative serum angiotensinogen, epinephrine, renalase/epinephrine ratio, and BP in patients who underwent laparoscopic cyst decortication. Materials and Methods: We included 20 patients with large SRC and 16 healthy individuals in this prospective study. Cysts were diagnosed by ultrasonography and characterized using computed tomography. Blood and urine samples were collected during pre- and postoperative periods. In addition, 12-hour ambulatory BP values were recorded. Serum angiotensinogen, renalase, and epinephrine levels were measured by the enzyme-linked immunosorbent assay method. Results: There was no statistically significant difference in angiotensinogen and renalase levels between patient and control groups (p=0.205, p=0.163, respectively), but preoperative renalase/epinephrine ratio was significantly higher in patients (p=0.006) than in the control group. In addition, renalase/epinephrine ratio was significantly lower in the postoperative period (p=0.018). Univariate and multivariate logistic regression analyses demonstrated that a higher renalase/epinephrine ratio was associated with the presence of SRC (p=0.028, p=0.016, respectively). Conclusion: A high renalase/epinephrine ratio may be associated with the presence of large SRC. We think that renalase may be a biomarker in the management of SRC and decision making in surgical procedures. Association of renalase with large SRC should be explored in future studies. WOS:000533604700008 2-s2.0-85087987241

Background: Transient elevation of aminotransferases, alkaline phosphatase and/or bilirubin are common findings post living donor liver transplantation, however, when enzymes showed marked or prolonged elevation, complications should be considered including acute rejection, hepatic artery throm-bosis, infections or recurrence of the original disease.Aim of the Study: To demonstrate whether serum renalase can be used as a potential biomarker of hepatocellular inflam-mation following living donor liver transplantation especially when combined with the standard LFT, CRP & TLC.Patients and Methods: The study was performed on 50 patients with End Stage Liver Disease (ESLD) undergone Living Donor Liver Transplantation (LDLT). Measurement of CBC, CRP, LFT and KFT were done daily for seven days and three months following liver transplantation. Immunoassay of serum renalase, six hours, one week and three months after transplantation.Results: By comparing different laboratory data on day seven and third month to laboratory data on day one post-living donor liver transplantation, there was a statistically significant decline regarding AST, ALT, INR reflecting graft function, our study also revealed statistically significant positive correlation between serum Renalase levels and CRP and total leukocyte count three months after transplantation.Conclusion: Serum renalase in the blood may help in early detection and possible prevention of hepatocellular inflammation and injury. In the future serum renalase may help in diagnosing acute cellular rejection post-living donor liver transplantation to improve the clinical outcomes of such major procedure.

Background: Ischemia refers to diminished blood supply, causing a lack of oxygen and when blood supply is re-established this is reperfusion. The Ischemia-Reperfusion (I/R) process is a common event after living donor liver transplantation, trauma, and hemorrhagic shock. Renalase, a ubiquitous flavoprotein, is highly expressed in kidney, liver, heart, skeletal muscles and adipose tissues. Renalase has been verified that it is the only enzyme involved in the catecholamine metabolism that can be secreted into the blood cycle hitherto.Considering renalase close relationship with oxidative stress, renalase is thought to play a role, or at least responsive, in the process of hepatic ischemia reperfusion injury.Aim of Study: To demonstrate whether serum Renalase can be used as a potential biomarkers of hepatic ischemia reperfusion injury following living donor liver transplantation especially when combined with the standard LFT panel.Patients and Methods: The present study was conducted on 50 patients with End Stage Liver Disease (ESLD) under-going Living Donor Liver Transplantation (LDLT). Patients were evaluated pre-operatively laboratory by using the Child-Pugh score and Model for End-Stage Liver Disease (MELD) Score and radiological by abdominal Doppler ultrasonography. Intra-operative evaluation of patients included: Operative details including ischemia time, intraoperative bleeding and amount of blood transfused. Post-operative workup included daily examinations as regards vital signs, drains and fluid balance. Daily measurement of CBC, LFT and KFT was done for seven days.Results: By comparing different laboratory data day seven to laboratory data on day one post-living donor liver trans-plantation, there was a statistically significant decline regarding AST, ALT, INR reflecting graft function, our study demon-strated no statistically significant correlation between serum Renalase levels and operative ischemia time predisposing to ischemia reperfusion injury.Conclusion: Clinical treatment decisions based on the serial detection of renalase activities in the blood did not help in early detection and possible prevention of hepatic ischemia reperfusion injury post-living donor liver transplantation to improve the clinical outcomes of liver transplantation.

Background: Renalase is a catecholamine-metabolising enzyme, but its possible association with atrial fibrillation (AF) remains unknown. Aim: We sought to evaluate plasma renalase concentration in patients with AF undergoing pulmonary vein isolation (PVI) with respect to AF clinical characteristics, left atrial (LA) remodelling, and PVI efficacy. Methods: This case-control study included 69 patients (median age 58 years) with either paroxysmal (89%) or persistent (11%) AF, referred for PVI, and a control group consisting of 15 patients without AF, matched for age, sex, and comorbidi­ties. An evaluation of transthoracic echocardiography with LA speckle tracking and plasma renalase concentration using an enzyme-linked immunosorbent assay was performed. AF recurrence was defined as any AF episode on seven-day electro­cardiographic monitoring at six-month follow-up. Results: Renalase level was higher in the study group than in the control group (mean 27.99 vs. 21.48 μg/mL, p = 0.004), but it was lower in patients with persistent AF (19.05 vs. 28.77 μg/mL; p = 0.023) and among patients with AF episodes di­rectly preceding PVI (24.50 vs. 29.66 μg/mL; p = 0.04). Renalase concentration within the first quartile was associated with higher mean heart rate (70 vs. 61 bpm, p = 0.029), greater AF burden (36.9% vs. 9.3%, p = 0.027), greater LA diameter (41.1 vs. 37.9 mm, p = 0.011), and a trend towards less negative global LA strain (–9.4 vs. –13.5, p = 0.082). Logistic regres­sion revealed that global four-chamber LA strain was the only independent predictor of renalase variability (p = 0.0045). Renalase concentration did not predict AF recurrence at six-month follow-up (area under curve [AUC] = 0.614, p = 0.216). Conclusions: Low renalase level may be associated with impaired rate control, higher AF burden, and advanced LA remodel­ling in AF patients undergoing PVI, but it does not predict sinus rhythm maintenance.

Background: Hypertension develops at a rate of 33 to 70% after Coronary artery bypass grafting (CABG) operations. One of the most commonly used drugs to control hypertension is sodium nitroprusside (SNP). Additionally, renalase enzyme destroys catecholamines and mediates the regulation (reduction) of blood pressure. Thus, this clinical study aims to reveal how renalase, catecholamines and nitric oxide (NO) change and how certain hemodynamic parameters are affected in randomly and prospectively selected cases who are administered SNP for the treatment of blood pressure elevation within 6 to 8 hours after CABG surgery.Methods: The study included 26 patients who developed hypertension after CABG, 12 patients who had normal blood pressure after CABG, and 22 healthy individuals. Renalase and catecholamine levels of the patients were measured using ELISA method and NO levels were determined by spectrophotometry.Results: Renalase and NO levels of the patients who developed hypertension after CABG were found statistically significantly lower than those of healthy controls and patients who did not develop hypertension after CABG, while catecholamine levels were significantly higher in the former. After SNP was started, renalase and NO levels increased, and a significant decrease was observed in the catecholamine levels. Additionally, administration of SNP produced a slight increase in the heart rate and a decrease in systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and means arterial pressure (MAP).Conclusion: SNP elevates NO and renalase levels; thus, administration of renalase preparations, which act in the destruction of catecholamines to contain persistent hypertension that develops in association with catecholamine elevation after CABG surgery, along with SNP and other medications used to lower blood pressure can be an effective therapeutic method to control hypertension.

Endothelin-1 (ET-1) is associated with endothelial dysfunction and vasoconstriction. Increased circulating ET-1 levels are associated with long-term cardiovascular mortality. Renalase, released from kidney, metabolizes catecholamines and regulates blood pressure. An increase in circulating renalase levels has been reported in patients with chronic kidney disease (CKD) and is associated with coronary artery disease (CAD). We hypothesized the existence of a synergistic effect of serum renalase levels and CKD on ET-1 levels in patients with CAD. We evaluated 342 non-diabetic patients with established CAD. ET-1 and renalase levels were measured in all patients after an overnight fast. Patients with CKD had higher ET-1 (1.95 ± 0.77 vs. 1.62 ± 0.76 pg/ml, P the median of 36.2 ng/ml) exhibited the highest serum ET-1 (P value for the trend

The relationship between the levels of renalase and changes in proteinuria, hypertension, renal function, renal tubular epithelial cell apoptosis and B-cell lymphoma-2 (Bcl-2) expression was investigated in patients (chronic nephritis, primary nephrotic syndrome or other kidney disease) that underwent renal biopsy. The study group comprised 72 patients undergoing renal biopsy. Patient profiles and renal function were collected. Concentrations of renalase and Bcl-2 were measured by immunohistochemistry. Tubular injury was detected by periodic acid Schiff staining (PAS) and renal tubular epithelial cell apoptosis was assessed by TUNEL assay. The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues. There was a positive linear relationship between renalase and some serum and cardiac indices; a negative correlation was found between age, eGFR, Ccr and 24-h urinary protein. Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase. The results showed that renalase probably increased the expression of Bcl-2. By two independent samples t-test, renalase levels were significantly increased in the non-hypertension group than in the hypertension group. One-way ANOVA showed that renalase expression was higher in samples with Lee's grade III than in those with Lee's grade V. The expression of renalase was significantly decreased in patients who underwent renal biopsy, and was also associated with blood and renal function. The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway, finally achieving the purpose of delaying the progress of renal failure.

Renal interstitial fibrosis (RIF) is a common pathway for progression of chronic kidney disease (CKD) to end-stage renal disease. In our previous study, it has been provided that renalase can ameliorate renal interstitial fibrosis in unilateral ureteral obstruction (UUO) rats. The other mechanism of renalase to alleviate renal fibrosis should be explored. In this study, we evaluated the role of oxidative stress in UUO rats and epithelial–mesenchymal transition (EMT) in human proximal renal tubular epithelial (HK-2) cells and examined the association of renalase. Oxidative stress could induce EMT and fibrosis in HK-2 cells. In the UUO model, oxidative stress occurred and maintained at a high level leading to RIF. Administration of renalase by adenovirus significantly attenuated oxidative stress and further in vitro study showed that renalase can exert anti-fibrosis by inhibiting oxidative stress. Our results prompt another mechanism of anti-fibrotic renal protection of renalase, which may be partly associated with inhibiting oxidative stress. These data provided another theoretical basis that supplementation with exogenous renalase may be a promising strategy for slowing or halting the progression of CKD.

Aim The purpose of the study was to evaluate urinary renalase concentration before and after coronary angiography/percutaneous coronary interventions (CA/PCI) in patients with coronary artery disease (CAD) and preserved kidney function and verify its potential application as contrast-induced acute kidney injury (CI-AKI) diagnostic marker. Methods This prospective study comprised 95 consecutive patients (69.5% men; median age 65 years) with CAD submitted to elective or urgent CA/PCI. Data regarding 128 clinical variables were obtained. Urine samples were collected on admission and 6 h after CA/PCI and tested for urinary renalase using ELISA method, which was expressed as renalase-to-creatinine ratio. The CI-AKI diagnosis was based on ≥50% relative or ≥0.3 mg/dl absolute increase of serum creatinine concentration 48 hours following the procedure. Results Nine patients developed CI-AKI (9.5%). In comparison to baseline values, urinary renalase-to-creatinine ratio significantly decreased 6 h following CA/PCI, (2843.6 vs.1540.7 ng/mg,p

Aim To measure the level of serum renalase and to clarify its relation to lupus nephritis (LN) activity and histopathological classification. Patients and methods This study was carried out on 40 patients with systemic lupus erythematosus (SLE), diagnosed according to systemic lupus international collaborating clinics classification criteria (SLICC) criteria, and 20 healthy controls. They were 20 patients without nephritis and 20 patients with LN (17 active and three inactive LN). Venous blood samples were taken from all participants for complete blood count, erythrocyte sedimentation rate, kidney function, anti-double-stranded DNA, C3, C4, and renalase level. The serum renalase levels were determined by enzyme-linked immunosorbent assay. Assessments of protein in 24-h urine collection and protein/creatinine (P/C) ratio were done. Renal biopsies were obtained from patients with LN, with staging and activity and chronicity indices assessment. SLE disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index, and LN activity was estimated by renal Systemic Lupus Erythematosus Disease Activity Index. Results Renalase levels were higher in patients with LN than both patients with SLE without LN and control group. The serum renalase levels of patients with LN were positively correlated with P/C ratio, 24-h proteinuria and C3, but negatively correlated with Systemic Lupus Erythematosus Disease Activity Index. For patients with active LN, there was no significant correlation between their serum renalase levels and the indicators of renal activity, including erythrocyte sedimentation rate, proteinuria, P/C ratio, anti-double-stranded DNA, C3, C4, and activity index of renal biopsy. The median of renalase as a marker for diagnosis of LN was 134.65, with a cutoff value of 100 µg/ml. Conclusion Serum renalase may be involved in LN pathogenesis but was not a good predictor for either LN activity or various stages of LN histopathology.

Introduction. We have previously reported that rs10887800 and rs2576178 renalase (RNLS) single nucleotide polymorphisms (SNPs) are associated with the susceptibility to arterial hypertension (HY) and coronary artery disease (CAD) in hemodialyzed patients (HD). However, the underlying mechanism of this link remains undefined. Aim. In the present study we examine the influence of above-mentioned RNLS gene variants on plasma renalase level in subgroups of HD patients affected by HY and CAD. Material and methods. In total, 309 hemodialyzed patients participated in the study (157 males and 152 females, mean age 64.1±14.10 years). Rs10887800 and rs2576178 RNLS gene polymorphisms were genotyped using PCR-RFLP method. Plasma RNLS level was assessed by ELISA (USCN Life Science Inc., Wuhan, China). The data were analyzed using SPSS Statistics 23. Results. Regarding rs10887800 polymorphism, hypertensive AA homozygotes had significantly lower plasma RNLS level (28.93±9.94 μg/mL) compared to AG (34.06±12.79 μg/mL) and GG carriers (36.54±12.01 μg/mL), p=0.002. Among CAD patients no differences in plasma RNLS concentrations between rs10887800AA, AG and GG carriers were observed (31.52±10.95 μg/mL, 34.75±13.37 μg/mL, 34.44±13.10 μg/mL, respectively), p=0.615. For the rs2576178 variant, both HY and CAD participants did not differ in terms of plasma RNLS levels with regard to the particular genotypes, p>0.050. Conclusion. Obtained results extend our previous findings and indicate for the first time that rs10887800 RNLS gene variant modifies the level of plasma RNLS in hemodialyzed patients with HY but not in those with CAD. The study provides, thus, a new insight into the potential mechanisms through which RNLS gene variants modulate the risk of cardiovascular diseases among patients with end-stage kidney disease.

Acute pancreatitis is a disease associated with inflammation and tissue damage. One protein that protects against acute injury, including ischemic injury to both the kidney and heart, is renalase, which is secreted into the blood by the kidney and other tissues. However, whether renalase reduces acute injury associated with pancreatitis is unknown. Here, we used both in vitro and in vivo murine models of acute pancreatitis to study renalase's effects on this condition. In isolated pancreatic lobules, pretreatment with recombinant human renalase (rRNLS) blocked zymogen activation caused by cerulein, carbachol, and a bile acid. Renalase also blocked cerulein-induced cell injury and histological changes. In the in vivo cerulein model of pancreatitis, genetic deletion of renalase resulted in more severe disease, and administering rRNLS to cerulein-exposed WT mice after pancreatitis onset was protective. Because pathological increases in acinar cell cytosolic calcium levels are central to the initiation of acute pancreatitis, we also investigated whether rRNLS could function through its binding protein, plasma membrane calcium ATPase 4b (PMCA4b), which excretes calcium from cells. We found that PMCA4b is expressed in both murine and human acinar cells and that a PMCA4b-selective inhibitor worsens pancreatitis-induced injury and blocks the protective effects of rRNLS. These findings suggest that renalase is a protective plasma protein that reduces acinar cell injury through a plasma membrane calcium ATPase. Because exogenous rRNLS reduces the severity of acute pancreatitis, it has potential as a therapeutic agent.

Dysregulated expression of the secretory protein renalase can promote pancreatic ductal adenocarcinoma (PDAC) growth in animal models. We characterized renalase expression in premalignant and malignant PDAC tissue and investigated whether plasma renalase levels corresponded to clinical PDAC characteristics. Renalase immunohistochemistry was used to determine the presence and distribution of renalase in normal pancreas, chronic pancreatitis, PDAC precursor lesions, and PDAC tissues. Associations between pretreatment plasma renalase and PDAC clinical status were assessed in patients with varied clinical stages of PDAC and included tumor characteristics, surgical resection in locally advanced/borderline resectable PDAC, and overall survival. Data were retrospectively obtained and correlated using non-parametric analysis. Little to no renalase was detected by histochemistry in the normal pancreatic head in the absence of abdominal trauma. In chronic pancreatitis, renalase immunoreactivity localized to peri-acinar spindle-shaped cells in some samples. It was also widely present in PDAC precursor lesions and PDAC tissue. Among 240 patients with PDAC, elevated plasma renalase levels were associated with worse tumor characteristics, including greater angiolymphatic invasion (80.0% vs. 58.1%, p = 0.012) and greater node positive disease (76.5% vs. 56.5%, p = 0.024). Overall survival was worse in patients with high plasma renalase levels with median follow-up of 27.70 months vs. 65.03 months (p < 0.001). Renalase levels also predicted whether patients with locally advanced/borderline resectable PDAC underwent resection (AUC 0.674; 95%CI 0.42–0.82, p = 0.04). Overall tissue renalase was increased in both premalignant and malignant PDAC tissues compared to normal pancreas. Elevated plasma renalase levels were associated with advanced tumor characteristics, decreased overall survival, and reduced resectability in patients with locally advanced/borderline resectable PDAC. These studies show that renalase levels are increased in premalignant pancreatic tissues and that its levels in plasma correspond to the clinical behavior of PDAC.

Background/Aims: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines, therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the production and metabolism of renalase. The aim of this study was to examine the effect of bilateral nephrectomy on renalase levels in the serum and erythrocytes of hemodialysis patients. Methods: This study included 27 hemodialysis patients post-bilateral nephrectomy, 46 hemodialysis patients without nephrectomy but with chronic kidney disease and anuria and 30 healthy subjects with normal kidney function. Renalase levels in the serum and erythrocytes were measured using an ELISA kit. Results: Serum concentrations of renalase were significantly higher in post-bilateral nephrectomy patients when compared with those of control subjects (101.1 ± 65.5 vs. 19.6 ± 5.0, p &lt, 0.01). Additionally, renalase concentrations, calculated per gram of hemoglobin, were significantly higher in patients after bilateral nephrectomy in comparison with those of healthy subjects (994.9 ± 345.5 vs. 697.6 ± 273.4, p = 0.015). There were no statistically significant differences in plasma concentrations of noradrenaline or adrenaline. In contrast, the concentration of dopamine was significantly lower in post-nephrectomy patients when compared with those of healthy subjects (116.8 ± 147.7 vs. 440.9 ± 343.2, p &lt, 0.01). Conclusions: Increased serum levels of renalase in post-bilateral nephrectomy hemodialysis patients are likely related to production in extra-renal organs as a result of changes in the cardiovascular system and hypertension.

Inflammation and endothelial dysfunction may play an important role in the multifactorial pathogenesis of hypertension. Endocan is also thought to play a role in cell adhesion and inflammatory disorders. The aim of the study was to compare endocan concentrations in patients with primary hypertension and healthy volunteers. There were 104 patients with hypertension (study group) and 21 healthy volunteers (control group). The correlation between endocan, catecholamines, and blood pressure control in patients with primary hypertension and the control group was analyzed. The median endocan concentration in the study group (2.03 ng/mL) was significantly higher than in the control group (1.09 ng/mL, P = .0001). Endocan concentration was correlated positively with renalase ( r = .2, P = .047) and norepinephrine ( r = .25, P = .02). Negative correlation was observed between endocan and body mass index ( r = −.25, P = .016) and leukocyte count ( r = −.36, P = .0004). The present study reports higher plasma endocan concentration in patients with treated, well-controlled primary hypertension compared with healthy volunteers. The higher endocan concentration in the study group may reflect endothelial dysfunction in this population.

Renalase is a recently discovered flavin adenine dinucleotide (FAD)-dependent soluble monoamine oxidase. It is expressed principally in the kidney, but its expression in the heart, brain, and skeletal muscle has also been confirmed. It is thought that renalase is involved in cardiac function and control of systemic blood pressure primarily by metabolizing circulating catecholamines. Animal experiments have suggested the possibility that exercise is involved in renalase secretion, but this has not been confirmed in human studies. The principal aim of the present study was to investigate the relationship between exercise and renalase concentration in humans. Subjects were young men who were continuously training to run distances of 10-20 km; the total distance that was run in the present study was 30 km. Measurements were performed at four points (before running and after running 10 km, 20 km, and 30 km). The results of one-way analysis of variance examining repeated measurements of serum renalase concentration revealed significant differences (P = 0.007). A significant negative correlation between serum renalase concentration and estimated glomerular filtration rate, which indicates renal function, calculated using serum cystatin C concentration was noted. A significant positive correlation between serum renalase concentration and oxidative stress was observed in the period before exercise and after running 20 km. The present study verified the exercise-induced increase in serum renalase concentration in amateur runners who were continuously training.