Edyta Zbroch

Renalase, a novel enzyme involved in blood pressure regulation, is related to kidney function but not to blood pressure in hemodialysis patients.

Renalase, secreted by the kidney, degrades catecholamines and may play a role in the regulation of sympathetic tone and blood pressure. The aim of this study was to assess serum renalase levels in hemodialysis patients and their relationship to blood pressure control, type of antihypertensive therapy and the presence of residual renal function. Results: The mean serum renalase in the study cohort was significantly higher than in the control group (27.53 ± 7.18 vs. 3.86 ± 0.73 µg/ml, p < 0.001). The serum renalase concentration was significantly lower in patients with residual renal function when compared to the anuric patients. The type of hypotensive treatment (β-blockers, ACE inhibitors or AT1 receptor blockers) did not affect renalase levels. There was a significant inverse correlation between the serum renalase and age (r = –0.28, p = 0.023) and residual renal function (r = –0.327, p = 0.001). Renalase was not related to blood pressure, heart rate or hemodialysis vintage. Conclusion: Elevated renalase levels in HD patients may be due to impaired kidney function. Further studies are needed to prove or disprove the possible role of renalase in the pathogenesis of hypertension in patients with kidney diseases.

Renalase, Stroke, and Hypertension in Hemodialyzed Patients

Introduction: Hypertension and kidney disease have been associated with increased incidence of stroke. Renalase, a newly discovered hormone, is secreted by the kidney and circulates in blood. The aim of this study was to assess possible correlations between renalase, blood pressure, stroke, and cardiovascular status in prevalent hemodialyzed patients. Methods: Renalase was assessed using commercially available assay. Echocardiography was performed in each patient. Results: Serum renalase was significantly lower in patients with a history of stroke (21%) than in patients without it. Similarly, renalase was significantly lower in hypertensive patients (82%) when compared with normotensives. Serum renalase correlated with creatinine, residual renal function, and transferrin saturation. The only predictor of renalase in multiple regression analysis was the presence of hypertension explaining 90% of the renalase variations. Conclusions: Our preliminary results suggest that renalase, probably due to the sympathetic nervous system hyperactivity, could be associated with hypertension and cardiovascular complications, including stroke in hemodialyzed patients. However, further studies are needed to establish the possible role of renalase in these complications. Renalase is “a new postulated therapeutic target.”

Circulating levels of renalase, norepinephrine, and dopamine in dialysis patients.

Background: hRenalase may degrade catecholamines and regulate sympathetic tone and blood pressure (BP). The aim of the study was to assess dopamine (DA), norepinephrine (NE), and renalase in 75 hemodialysis (HD) and 26 peritoneal dialysis (PD) patients and their correlations with heart rate (HR), BP, a type of hypotensive therapy, and residual renal function. Methods: Renalase, DA, NE were studied using commercially available assays. Results: Renalase and NE were higher and DA was lower in dialyzed groups comparing to healthy volunteers. Hemodialysis patients had lower NE and higher renalase level. Norepinephrine was higher in anuric patients in HD group. Renalase correlated with dialysis vintage and inversely with residual diuresis. Dopamine correlated with residual diuresis in the whole study cohort, with HR in PD patients, with renalase in HD patients. Norepinephrine correlated with aortic diameter in PD patients. Norepinephrine was significantly higher in patients with coronary artery disease (CAD) in HD group. Hemodialysis population with CAD had lower NE and higher DA and renalase level than their PD counterparts. In the follow up, 27% of HD group died. Cardiac death was diagnosed in 17% and there was higher renalase level than in noncardiac death. Conclusions: Elevated level of circulating renalase in dialysis patients is rather related to kidney function and the sympathetic nervous system hyperactivity found in this population. The real excess of renalase in the pathogenesis of cardiovascular disorders in patients with chronic kidney disease still remains to be proven. If confirmed, it may give a new way for pathophysiological therapy.

Vascular adhesion protein-1 and renalase in regard to diabetes in hemodialysis patients

Introduction Vascular adhesion protein-1 (VAP-1) is a copper-containing semicarbazide-sensitive amine oxidase (SSAO) secreted by vascular smooth muscle cells, adipocytes, and endothelial cells with functional monoamine oxidase activity. Renalase, with possible monoamine oxidase activity, which breaks down catecholamines like SSAO, is also expressed in the endothelium as well as in the kidney. The aim of the study was to assess VAP-1 level and its correlation with renalase level in 60 hemodialyzed (HD) patients. Material and methods Complete blood count, urea, serum lipids, fasting glucose and creatinine were studied by the standard laboratory method in the hospital central laboratory. We assessed VAP-1 and renalase with commercially available assays. Results The mean level of VAP-1 as well as renalase was significantly higher in HD patients when compared to the control group (291.01 ±94.91 ng/ml vs. 158.34 ±56.89 ng/ml, p < 0.01; 27.53 ±9.394.91 µg/ml vs. 4.00 ±1.37 µg/ml, p < 0.001, respectively). In hemodialysis patients VAP-1 correlated with presence of diabetes (r = 0.27, p < 0.05), presence of hypertension (r = 0.32, p < 0.05), use of calcium channel blockers (r = 0.30, p < 0.05), use of β-blockers (r = 0.25, p < 0.05), ejection fraction (r = –0.38, p < 0.01), systolic blood pressure before (r = 0.52, p < 0.001) and after hemodialysis (r = 0.30, p < 0.01), and weight gain (r = 0.41, p < 0.01). Renalase was not significantly different in diabetic and non-diabetic patients or between hypertensive and normotensive patients. In multiple regression analysis VAP-1 was predicted 77% by serum ejection fraction and fibrinogen. Conclusions Vascular adhesion protein-1, elevated in patients on hemodialysis, was predominantly dependent on blood pressure and diabetes, both factors associated with endothelial damage and promoting cardiovascular complications. Renalase appeared to be unrelated to VAP, at least in the HD population.

Hypertension in solid organ transplant recipients

Hypertension (HT) is one of the most frequent complications of solid organ transplantation; about 70-90% of this population have high blood pressure or require antihypertensive therapy. Abnormal blood pressure is a potent non-immunological risk factor directly related to patient and graft survival. The etiology of hypertension after orthotopic heart transplantation is multifactorial and varies depending on the time following transplantation. In the early period after transplantation, hypertension is generally related to intravascular volume expansion and persistently increased systemic vascular resistance. Other factors predominant in kidney allograft recipients include: donor age, donor familial history of hypertension, transplant renal artery stenosis, graft function, the recurrence or de novo appearance of glomerulonephritis in transplanted kidney, and post-biopsy arteriovenous fistula. In liver and heart transplantation, hypertension is mainly due to impaired kidney function, with all its consequences. Another contributing factor is immunosuppressive regimen based on calcineurin inhibitors and steroids. The management of post-transplant hypertension usually requests non-pharmacological and pharmacological treatment. In this review, the pathogenesis and treatment of post-transplant hypertension in solid organ transplantation is presented.

Insulin-Like Growth Factor System Components in Relation to Erythropoietin Therapy and Bone Metabolism in Dialyzed Patients and Kidney Transplant Recipients

Insulin-like growth factor (IGF) system components appear to be the most important regulators of bone cell function. On the other hand, IGF-1 is shown to be an important regulator for erythropoiesis. The aim of the study was to examine the relationships between IGF system, requirements of erythropoietin, endogeneous erythropoietin levels, bone metabolism assesed by biochemical markers, markers of nutrition such as cholesterol and albumin in recombinant human erythropoietin (rHuEPO)-treated patients maintained on chronic hemodialyses or peritoneal dialyses as well as in kidney transplant recipients. The studies were performed on 79 chronically hemodialyzed patients; 28 of them did not receive rHuEPO, 51 subjects received rHuEPO, 34 patients on continuous ambulatory peritoneal dialysis (CAPD), 16 of them did not receive rHuEPO, 18 were given rHuEPO and 46 kidney allograft recipients. Endogeneous erythropoietin concentration, bone-specific alkaline phosphatase and serum CrossLaps were assayed by ELISA. Intact PTH, osteocalcin, 1,25-(OH)2 D3, 25-OH D3, IGF-1, procollagen type I carboxy-terminal extension peptide (PICP) and procollagen type I cross-linked carboxy-terminal telopeptide (ICTP) were studied by RIA, whereas IGFBP-1 and IGFBP-3 concentrations were assayed by IRMA. We found a significantly higher IGF-1 and IGFBP-3 in rHuEPO-treated HD patients when compared to CAPD subjects given rHuEPO as well as to hemodialysis (HD) patients not treated with rHuEPO. IGF-1 was significantly higher in kidney transplant recipients when compared to dialyzed patients without rHuEPO therapy. IGFBP-1 was similar in all groups of patients (including kidney transplant recipients) studied. In CAPD patients not given rHuEPO concentrations of ICTP and PICP were significantly lower when compared to rHuEPO-treated CAPD subjects and HD patients not receiving rHuEPO therapy. Serum CrossLaps in CAPD patients treated with rHuEPO were significantly higher when compared to CAPD subjects without rHuEPO treatment and to kidney transplant recipients. In rHuEPO-treated CAPD subjects IGF-1 and IGFBP-1 correlated positively with serum CrossLaps (r = 0.61, p < 0.05 and r = 0.64, p < 0.05, respectively), whereas in hemodialyzed patients without rHuEPO a significant negative correlation between IGFBP-3 and serum CrossLaps was found (r = –0.69, p < 0.001) as well as between IGFBP-3 and aluminium (r = 0.51, p < 0.05), IGF-1 and ICTP (r = –0.43, p < 0.05). In conclusion, our data indicate a probable functional relationship between IGF system components, erythropoietin treatment in dialyzed patients and bone metabolism in renal replacement therapy in a form of hemodialyses, peritoneal dialyses and kidney transplantation. Dialyzed patients exhibit more pronounced renal osteodystrophy than kidney allograft recipients. IGF system components are influenced by erythropoietin therapy, but are not related to serum erythropoietin levels and rHuEPO requirements.

Leptin and Serum Erythropoietin in Hemodialyzed and Peritoneally Dialyzed Uremic Patients during rHuEPO Therapy

Leptin produced by fat cell has an unanticipated role in hematopoietic system development. We examined the relationships between leptinemia and requirements of erythropoietin (Epo), endogenous Epo levels as well as markers of inflammation: C-reactive protein, tumor necrosis factor α (TNFα) and interleukin-1 (IL-1) in rHuEPO-treated patients maintained on chronic hemodialyses or peritoneal dialyses. The studies were performed on 51 chronically hemodialyzed patients, 20 of them did not receive rHuEPO, 31 subjects received rHuEPO, and 22 patients on CAPD, 13 of them did not receive rHuEPO, 9 subjects were given rHuEPO. In hemodialyzed patients (Epo and Non-Epo group) leptin levels were significantly higher when compared to CAPD patients (Epo and Non-Epo group, respectively). Leptin in peritoneal fluid was significantly higher in the Non-Epo group. In ultrafiltrate, leptin levels were below the detection limit of 0.5 ng/ml. Epo levels in the HD + Epo group were significantly lower than in the HD + Non-Epo group and CAPD + Epo group. TNFα and IL-1 concentrations were significantly lower in both groups of CAPD patients when compared to respective HD groups. Treatment with rHuEPO resulted in nonsignificant decline in serum leptin (p = 0.07 in HD and p = 0.08 in CAPD) and significant leptin loss in peritoneal fluid. It may be of clinical relevance in dialyzed patients. In both groups of Epo-treated patients, positive physiological correlation between leptinemia and BMI disappeared. Leptin levels do not correlate with rHuEPO requirements and serum Epo in dialyzed patients.

Age influence on renalase and catecholamines concentration in hypertensive patients, including maintained dialysis.

Background Hypertension in elderly patients is one of the main problems in cardiovascular diseases. The sympathetic nervous system hyperactivity seen in older patients is a known risk factor for hypertension and other cardiovascular events as well as chronic kidney disease. Renalase, secreted by the kidney and circulated in blood, may regulate the sympathetic tone by catecholamine degradation and in this way has an impact on cardiovascular and renal complications. Objective To assess the impact of age on renalase and catecholamine concentration in hypertensive patients, including those on dialyses and its possible relation to blood pressure control and cardiovascular disease. Methods The study cohort of 211 patients was divided into two groups according to age below 65 years (range 19–64) and above 65 years (range 65–86). The older group represented 38% of the whole studied population and 75% of them were dialyzed. The two groups of different ages were also divided into dialysis and nondialysis subgroups. The serum renalase, dopamine, and norepinephrine concentration together with blood pressure value and echocardiography were assessed. Results Patients aged 65 years and more had higher renalase (20.59 vs 13.14 µg/mL, P=0.02) and dopamine (41.71 vs 15.46 pg/mL, P<0.001) concentration as well as lower diastolic blood pressure (75.33 vs 85 mmHg, P=0.001), advanced abnormalities in echocardiography, and more often suffered from diabetes and coronary artery disease. The significant correlation between age and renalase (r=0.16; P=0.019), norepinephrine (r=0.179; P=0.013), and dopamine (r=0.21; P=0.003) was found in the whole study population. In the nondialysis subgroup, 44% had chronic kidney disease, mostly in the stage 2 (83%). There was a significantly higher norepinephrine concentration (1.21 vs 0.87 ng/mL; P=0.008) in older patients of that population. In the dialysis subgroup, there were no differences between renalase and catecholamine level but older participants had lower diastolic blood pressure (69 vs 78 mmHg, P=0.001) and ejection fraction (51% vs 56.8%, P=0.03). Conclusion The elevated renalase level in older hypertensive patients is related rather to kidney function and cardiovascular diseases than to age itself. Thus, renalase appears to be the possible new marker of these indications in this special population.

Opinions of Town Residents on Organ Transplantation

INTRODUCTION Organ transplantation is connected with many very difficult ethical and social issues that evoke a lot of emotion. The aim of this work was to determine the knowledge and opinions of the 612 residents of selected towns in Podlaskie voivodeship (in northeastern Poland) on organ transplantation. MATERIAL AND METHODS A diagnostic poll with the use of a survey questionnaire was implemented in the study. The respondents were divided into 2 groups (towns <100,000 and >100,000 residents). RESULTS Respondents from larger towns were more often willing to donate organs of close relatives for transplantation than those from small towns (67.1% vs 32.9%; P = .022). Respondents with higher education levels accepted organ donation from close relatives after their death significantly often than those with no more than a primary education (46.7% vs 22.2%; P < .001). Of the respondents, 83% would agree to donation after death and to donating their own organs (higher with primary education, 90.6% vs 63.5%; P < .001). Of respondents from big towns, 61.0% have informed their family of the decision for donation after death compared with 38.5% of respondents from small towns. Respondents with higher education significantly more often informed their family of such decision than persons with primary education (60.9% vs 42.9%; P < .007). CONCLUSIONS More emphasis should be on educating the communities living in small towns and people with primary and vocational education, because an adequate level of knowledge is a significant factor influencing the readiness to give ones organs for transplantation.

Endocan Concentration in Patients With Primary 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.