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Background: The most common complications of chronic kidney disease (CKD) are hypertension and cardiovascular (CV) disorders. Renalase is produced and released by the kidney and also cardiomyocytes. Renalase deficiency was claimed to be responsible for hypertension and CV complication in CKD. There are contradictory data about serum renalase because of low activity and high levels revealed in hypertensive patients with CKD. We assessed serum renalase concentration in objects with CKD after one-side and both-side nephrectomy (on haemodialysis [HD]), or hemodiafiltration (HDF), in urine and ultrafiltrate in hemodialysis objects. We also evaluated the influence of hemodialysis sessions on renalase concentrations., Methods: The concentration of renalase in plasma, ultrafiltrate and urine of 100 hemodialysis patients was assessed by commercially accessible test. We evaluated renalase in 17 HDF objects and 24 healthy controls. Western Blot test was also used to assess renalase concentration., Results: Ultrafiltrate in hemodialysis objects contained renalase and there was no impact of dialysers' type (high-flux and low-flux). Renalase concentration of urine in control group was higher than in hemodialysis objects (n=60). The anuric group had higher renalase concentration comparing to those with remaining diuresis (p<0.001). Univariate analysis revealed the correlation between renalase concentration in plasma and in urine (r=-0.28, p<0.05) and ultrafiltrate renalase in hemodialysis group and between renalase in urine in the control group (r=0.61, p<0.01). There was a correlation between urinary renalase and residual diuresis, hemodialysis sessions non-significantly lowered renalase, the type of heparin had no effect on serum renalase levels. HDF patients had significantly lower renalase than HD patients. In Western blot analysis we found that patients after bilateral nephrectomy had the highest renalase, followed by unilateral nephrectomy., Conclusion: Kidneys eliminate renalase and it is possible that the increased renalase has the impact on cardiovascular diseases in chronic kidney disease.

Introduction: All living organisms have evolved sophisticated mechanisms to maintain appropriate iron levels in their cells and within their body. Recently our understanding of iron metabolism has dramatically increased. Overt labile plasma iron (LPI) represents a component of non-transferrin bound iron (NTBI) that is both redox active and chelatable, capable of permeating into organs and inducing tissue iron overload. The LPI measures the iron-specific capacity of a given sample to produce reactive oxygen species. We studied for the first time NTBI correlations with markers of iron status and inflammation in prevalent hemodialyzed patients., Material and Methods: Complete blood count, urea, serum lipids, fasting glucose, creatinine, ferritin, serum iron, total iron binding capacity (TIBC) were studied by standard laboratory method. The NTBI was assessed commercially available kits from Aferrix Ltd in Tel Aviv, Israel. A test result of 0.6 units of LPI or more indicates a potential for iron-mediated production of reactive oxygen species in the sample., Results: Patients with LPI units ≥ 0.6 had higher serum iron, erythropoiesis stimulating agents (ESA) dose, ferritin, high-sensitivity C-reactive protein (hsCRP), hepcidin and lower hemojuvelin. In hemodialyzed patients NTBI correlated with hsCRP (r = 0.37, p < 0.01), ferritin (r = 0.41, p < 0.001), IL-6 (r = 0.43, p < 0.001). In multivariate analysis predictors of NTBI were hemoglobin and alkaline phosphatase, explaining 58% of the variability., Conclusions: Elevated NTBI in HD may be due to disturbed iron metabolism. Anemia and liver function might also contribute to the presence of NTBI in this population.

Background: In patients after kidney transplantation, anemia is relatively common and is associated with impaired kidney function, subclinical inflammatory state, and immunosuppressive treatment. Zonulin-prehaptoglobin-2, a newly discovered protein, is necessary for integrity of intracellular tight junctions in the gut. Taking into consideration iron metabolism, including its absorption in the gut, we designed a cross-sectional study to look for the possible interactions among zonulin, iron status, and anemia in kidney transplant recipients., Methods: The study was performed on 72 stable kidney transplant recipients and 22 healthy volunteers. Zonulin, iron status, and inflammatory markers were assessed with the use of commercially available kits., Results: Zonulin was significantly lower in kidney allograft recipients than in healthy volunteers (P < .001). Zonulin correlated with systolic blood pressure (r = -0.33; P < .05), thyroid-binding globulin (r = 0.24; P < .05), hematocrit (r = 0.28; P < .005), hemoglobin (r = 0.32; P < .01), total protein (r = -0.33; P < .01), erythrocyte count (r = 0.26; P < .05), and fasting glucose (r = -0.25; P < .05). Zonulin was not affected by sex, type of immunosuppressive therapy, presence of diabetes, coronary artery disease, heart failure, hypertension, or cause of end-stage renal disease. Zonulin was not related to any of the iron parameters studied. In multiple regression analysis, predictors of zonulin were total protein and thyroglobulin-binding protein, explaining 46% of variation., Conclusions: Zonulin, with its poorly defined function, does not seem to play a role in the anemia in kidney allograft recipients; however, it seems to be related to the absorption process in the gut.

Background: Fibroblast growth factor (FGF) 23 is a newly discovered member of the FGF family. Klotho is a cofactor of FGF23. Activation of the FGF23-Klotho system is responsible for negative phosphate balance. In addition, FGF23 appears to be a risk factor for cardiovascular complications. The aim of this study was to assess levels of FGF23 and Klotho in stable kidney transplant recipients on triple immunosuppressive therapy in relation to comorbidities and markers endothelial dysfunction. Healthy volunteers served as a control group., Methods: Hemoglobin, urea, and creatinine were studied with the use of standard laboratory methods in the hospital central laboratory. We assessed FGF23 and Klotho, markers of endothelial function/injury von Willebrand factor (vWF), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and interleukin (IL) 6, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and copeptin with the use of commercially available assays., Results: FGF23 was significantly higher and Klotho significantly lower in kidney transplant recipients compared with healthy volunteers. FGF23 correlated with copeptin (r = 0.28; P < .05), IL-6 (r = 0.39; P < .01), VCAM (r = 0.36; P < .01), time after transplantation (r = 0.31; P < .05), platelet count (r = 0.31; P < .05), mean corpuscular volume (r = -0.40; P < .01), and phosphate (r = 0.31; P < .05). Klotho correlated with NT-proBNP (r = 0.38; P < .01), vWF (r = -0.26; P < .05), calcium (r = -0.39; P < .01), and age (r = 0.45; P < .001). FGF23 was significantly higher and Klotho significantly lower in patients with estimated glomerular filtration rate (eGFR) >60 mL/min compared with patients with eGFR <60 mL/min., Conclusions: Disturbances in the FGF23-Klotho system appeared to be related to the endothelial cell injury. Thus they are involved not only in pathogenesis of the metabolic bone disease but also in cardiovascular complications, particularly in kidney disease.

Background: YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesion of atherosclerosis. Because cardiovascular mortality is the main cause of death, there are no data on kidney transplant recipients, so the aim of the study was to assess YKL-40 in that population, with particular attention being paid to the relationship with endothelial damage., Methods: We studied 68 patients after kidney transplantation. Complete blood count, creatinine, lipids, and fasting glucose were studied with the use of standard laboratory methods. We assessed YKL-40; markers of inflammation high-sensitivity C-reactive protein (hs-CRP), von Willebrand factor, thrombomodulin, interleukin-6, intracellular adhesion molecule, and vascular cell adhesion molecule; markers of hemostasis plasmin-antiplasmin complexes, thrombin-antithrombin complexes, prothrombin fragments 1+2; and marker of kidney function neutrophil gelatinase-associated lipocalin (NGAL) with the use of commercially available assays., Results: Mean levels of YKL-40 were significantly higher in kidney allograft recipients than in the control group (P < .001). YKL-40 was also significantly higher in patients with coronary artery disease, hypertension, and diabetes compared with their counterparts without these diseases. YKL-40, in univariate analysis, was related to NGAL, protein Z, plasmin-antiplasmin complex, mean corpuscular volume, cyclosporine level, and hs-CRP. YKL-40 was not related to serum lipids, markers of endothelial cell injury, or causes of end-stage renal failure. YKL-40 was predicted by cyclosporine level, NGAL, and hs-CRP, explaining 37% of the variation., Conclusions: Elevated YKL-40 may contribute to enhanced risk of cardiovascular complication, mainly owing to endothelial cell injury and inflammation in patients after kidney transplantation treated with calcineurin inhibitors.

Purpose: Left main disease (LMD) is a severe form of coronary artery disease (CAD). Fifty percent of patients with LMD treated conservatively die within 3-5 years of diagnosis. The aim of the study was to assess the influence of type 2 diabetes on early and late (2-year) prognosis and the risk of complications after coronary artery by-pass graft (CABG) surgery in patients with LMD., Material/methods: We enrolled 257 patients diagnosed with LMD. 169 (67%) underwent CABG, 19 (8%) percutaneous coronary intervention (PCI) without left main stem protection. 30 (12%) patients had CABG previously. Patients treated with CABG were divided into two groups - with and without diabetes. There were 43 (25.4%) patients with diabetes and 126 (74.6%) without diabetes., Results: We observed more complications with wound healing (40.5% vs. 12.8%, p<0.001) and sternal dehiscence (23.8% vs. 4.0%, p<0.001) after CABG in patients with diabetes. There were no differences in 7-day, 30-day, 3-month and 1-year mortality. 2-Year mortality was also similar in both groups (11.6% vs. 11.1%, p=0.928). Patients with diabetes were more frequently hospitalized due to other reasons than angina (39.5% vs. 20.6%, p=0.014)., Conclusions: Patients with diabetes and LMD had more often complications with wound healing and sternal dehiscence after CABG than patients without diabetes. Type 2 diabetes did not influence early and late mortality in patients with LMD treated with cardiac surgery, but the presence of diabetes was associated with more frequent hospitalizations., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Contrast-induced nephropathy, or contrast-induced acute kidney injury (AKI), is an acute impairment of renal function as manifested by an increase in serum creatinine. Different urinary and serum proteins have been intensively investigated as possible biomarkers for the early diagnosis of AKI. Promising candidate biomarkers have the ability to detect an early and graded increase in tubular epithelial cell injury and to distinguish prerenal causes of AKI from acute tubular necrosis. In this article new, emerging biomarkers of contrast-induced AKI are presented and described, of which serum neutrophil gelatinase-associated lipocalin appears to be the most promising., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In 2003, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure established a definition of a new category of BP levels called 'prehypertension' (preHT) that included individuals with a systolic BP of 120-139 mm Hg or a diastolic BP of 80-89 mm Hg. Patients with preHT were considered to be at increased risk for progression to hypertension and in individuals with BP in the range 130/80 to 139/89 mmHg the risk of developing hypertension was twice as high as in subjects with lower values. Still then there has been a large debate whether the introduction of preHT was based on evidence and as a consequence, it was fully justified. It has been suggested that the term prehypertension may in many subjects create anxiety and a need for unnecessary medical visits and examinations. This group of patients is also very heterogeneous and it has been pointed out that subdividing preHT group into individuals with normal BP and high normal BP would much better correspond to the continuum of BP risk for CV disease. Finally, despite some data suggesting the potential benefits of antihypertensive therapy in patients with preHT (high normal BP), there are still no hard evidences on the outcome reduction by giving antihypertensive drugs in these individuals.

Screening is the systematic use of a test for a health problem or risk factor when no recognized signs or symptoms would indicate the presence of that problem or risk factor. Abnormal glucose metabolism can be documented years before the onset of overt diabetes. Nowadays, prediabetes can be subdivided into impaired fasting glucose or impaired glucose tolerance. Substantial number of subjects with either will progress to overt diabetes within years. Prediabetes bears also the increased risk of cardiovascular complications. Prehypertension is much newer term introduced by the seventh report of the Joint National Committee (JNC 7) published in 2003 as systolic blood pressure from 120 to 139 mmHg or diastolic blood pressure from 80 to 89 mmHg in adults (not receiving blood pressure-lowering treatment). Similarly prehypertension also increased the risk of cardiovascular complications and progression to hypertension. Chronic kidney disease is also highly prevalent mainly in the elderly. It is associated with important adverse outcomes such as cardiovascular mortality and morbidity. Factors associated with higher risk of chronic kidney disease include mainly hypertension, diabetes, obesity and older age. Early detection and diagnosis of chronic kidney disease may prevent the full blown disease and its end-stage requiring renal replacement therapy. The review focus on the problem of high risk population for development of diabetes, hypertension and whether time has come to focus also on the conditions predisposing to the development of chronic kidney disease.

VAP-1 (vascular adhesion protein-1) possesses semicarbazide-sensitive amine oxidase (SSAO) activity. It has also been found that serum VAP-1 was elevated in acute and chronic hyperglycemia and in patients with diabetes as well as in chronic kidney disease. Renalase, with possible monoamine oxidase activity, which breaks down catecholamines such as SSAO, is expressed in the endothelium as well as in the kidney. The aim of the study was to assess serum VAP-1 levels in peritoneally dialyzed (PD) patients and factors explaining its variability. This pilot study was performed on 25 peritoneally dialyzed patients, including 4 patients with type 2 diabetes. We found that the mean VAP-1 was significantly higher in chronic ambulatory peritoneal dialysis (CAPD) patients when compared to the control group (p<0.05). Dopamine was significantly lower in PD patients when compared to the healthy volunteers (p<0.05), whereas noradrenaline was significantly higher in PD patients relative to the healthy volunteers (p<0.01). There was a significant difference in the VAP-1 concentration in the group with and without residual renal function (p<0.05) as well as between 10 patients with hyperglycemia when compared to patients with normoglycemia (p<0.05). There was no effect of gender on the serum VAP-1 levels. In PD patients VAP-1 correlated with systolic blood pressure (r=-0.4, p<005), residual renal function (r=-0.62, p<0.05), and glucose (=0.54, p<0.05). We concluded that VAP-1, elevated in patients on PD, was predominantly dependent on residual kidney function and glucose level, factors both linked to endothelial damage and cardiovascular complications.

The blood pressure J-curve discussion has been ongoing for more than 30 years, yet there are still questions in need of definitive answers. On one hand, existing antihypertensive therapy studies provide strong evidence for J-curve-shaped relationships between both diastolic and systolic blood pressure and primary outcomes in the general hypertensive patient population, as well as in high-risk populations, including subjects with coronary artery disease, diabetes mellitus, left ventricular hypertrophy, and the elderly. On the other hand, we have very limited data on the relationship between systolic and diastolic blood pressure and stroke prevention. Moreover, it seems that this outcome is more a case of "the lower the better." Further large, well-designed studies are necessary in order to clarify this issue, especially as existing available studies are observational, and randomized trials either did not have or lost statistical power and were thus inconclusive.

Unlabelled: Anemia is more prevalent in renal transplant recipients than in GFR-matched chronic kidney disease patients. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia or inflammation. Growth differentiation factor 15 (GDF15) was recently identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. The aim of the study was to assess GDF15 levels with relation to iron parameters in 62 stable kidney allograft recipients maintained on triple immunosuppressive therapy., Methods: Complete blood count, urea, creatinine, and iron status were assessed by standard methods. We measured GDF15, hepcidin, hemojuvelin, IL-6 and NGAL with commercially available assays., Results: Mean levels of GDF15, NGAL, hepcidin and hemojuvelin were significantly higher in kidney allograft recipients when compared to the control group (p < 0.001 for all). GDF15 was significantly higher in patients with anemia according to the WHO definition when compared to their nonanemic counterparts (p < 0.05). GDF15 levels were not dependent on the type of immunosuppressive therapy. In univariate analysis GDF15 was related to kidney function (creatinine r = 0.39, p < 0.01, eGFR by MDRD r = -0.37, p < 0.01), urea (r = 0.39, p < 0.01), uric acid (r = 0.42, p < 0.01), hepcidin (r = -0.32, p < 0.01), IL-6 (r = 0.28, p < 0.05), hemoglobin (r = -0.32, p < 0.05), and NGAL (r = -0.35, p < 0.01). GDF15 was not related to serum iron, or ferritin. In multivariate analysis, hepcidin was found to be a predictor of GDF15. In conclusion, our preliminary data may suggest possible mutual relations between GDF15 and hepcidin in patients with kidney disease and that GDF15 might be involved in the pathogenesis of anemia in kidney allograft recipients. However, the role of inflammation should be also elucidated., (Copyright © 2013 S. Karger AG, Basel.)

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.

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.

Anemia is a highly prevalent disorder in recipients of renal allografts. Despite its frequent occurrence, there is still uncertainty with regard to treatment targets and treatment options. This includes questions on appropriate iron management, the choice and dosage of erythropoietin stimulating agents, criteria for the timing of treatment initiation and the targeted hemoglobin values. The review summarizes available data on recent therapeutic strategies for post transplant anemia, as well as for post transplant erythrocytosis, another hematological disorder, that has decreased in recent years., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)

Background: The aim of this study was to assess the value of the angiographically-derived Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score in predicting mortality and major adverse cardiac events (MACEs) during a 3-year follow-up of dialysis patients undergoing a percutaneous coronary intervention or coronary artery bypass graft operation. We compared the aforementioned results with the clinical Khan index., Methods: The SYNTAX score was calculated for 87 of 110 dialysis patients after coronary angiography., Results: The mean SYNTAX score was 12.75 ± 14.49. During the 3-year follow-up, 58% of the patients died, and 74% had at least 1 MACE. In a Kaplan-Meier survival analysis, the risk of death and MACEs increased in parallel with the SYNTAX score. A score greater than 12.75 was strongly associated with mortality and MACE (both Ps < 0.01). In receiver operating characteristic (ROC) curve analysis, the areas under the curves (AUCs) of the SYNTAX score and Khan index were significantly higher (both Ps < 0.001) than the area of diagnostic indifference. The predictive values for death as indicated by the SYNTAX score and the Khan index, respectively, were almost identical in the ROC analysis (AUC SYNTAX score, 0.6436; AUC Khan index, 0.6475; P = 0.9532). Areas under the ROC curves of both methods according to MACE were also significantly different from those for the random model (both Ps < 0.001)., Conclusions: The SYNTAX score is a powerful predictor of mortality and MACEs in dialysis patients undergoing percutaneous coronary intervention or coronary artery bypass graft during a 3-year follow-up. The score provides prognostic information similar to that provided by the Khan index., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Morbidity in end-stage renal disease (ESRD) diabetic patients is worse than in patients without diabetes mellitus (DM). This study aims to compare clinical, laboratory, and echocardiographic features between the ESRD patients with and without DM. Fifty-eight ESRD patients on dialysis were prospectively divided into two groups according to the presence of DM. Demographic, clinical, laboratory, and echocardiographic features (ejection fraction and wall motion score index) were compared between the two groups. Overall, 20 out of 58 patients (37.8%) with ESRD had DM. There were no significant differences between the patients with DM and those without DM when it comes to age (60.6 ± 10.6 vs. 59.0 ± 10.6 years, P = 0.665), ejection fraction (52.6% ± 12.8% vs. 54.2% ± 12.8%, P = 0.59), and wall motion score index (1.21 ± 0.3 vs.1.15 ± 0.3, P = 0.37). In multivariant analysis of the interventricular septum, posterior wall thickness and left atrium size correlated positively with DM. There was also no statistical difference in myocardial perfusion disturbances on real-time contrast echocardiography between the groups with and without DM (12 (60%) patients vs. 14 patients (36.8%), P = 0.079). Among diabetics 77.8% had significant atherosclerotic changes, while in the group without DM, only 38.1%, P = 0.01. From the laboratory parameters ferritin and high-sensitivity C-reactive protein levels were significantly higher in the group with DM, P = 0.014 and P = 0.026, respectively. Patients with ESRD and DM have significantly bigger left atrial size, thicker left ventricular walls, and higher serum ferritin and high-sensitivity C-reactive protein levels than the patients without DM. The aforementioned features may be possible risk factors for the development of adverse cardiac events in patients on hemodialysis.

Most patients on dialysis are hypertensive and their blood pressure (BP) control is often poor. Renalase is preferentially expressed in proximal tubules, but it is also present in glomeruli and distant tubules, as well as in cardiomyocytes, liver, and skeletal muscle. It had been proposed that renalase had a flavin adenine dinucleotide (FAD)-binding domain and that FAD was an essential cofactor for its stability and monoamine oxidase activity. It was reported that renalase, secreted by the kidney and circulating in the blood, degraded catecholamines and might play a role in the regulation of sympathetic tone and BP. It has been also proposed that renalase-coding gene is a novel susceptibility gene for essential hypertension and its variations may influence BP. In addition, polymorphisms of the renalase gene in hemodialysed patients were associated with hypertension. However, several unresolved and controversial issues still remain such as how to measure renalase and its physiological activity. Furthermore, there are few data on possible activators and/or inhibitors of renalase. We are at the very beginning of solving the problem of whether renalase is a causative factor of hypertension in kidney disease or just an innocent bystander. Therefore, more research is needed to establish whether renalase can become a useful therapeutic target.

The aim of the study was to collect retrospective data on renal anemia management, comorbidities and prospective data on 12-month standard care erythropoiesis-stimulating agent (ESA) therapy used in 398 hemodialyzed patients in selected Central and Eastern European countries (50 centers in 3 countries). Patients were divided into three groups according to ESA therapy start: group A-ESA (after start of hemodialysis, HD), B-ESA (within 3 months from start of HD), C-ESA (more than 3 months before HD). At the chronic kidney disease diagnosis, hemoglobin in all patients was 10.3 ± 2.3 g/dl; however, ferritin, iron, TSAT were within reference limits. Early ESA therapy (C) was administered to 10% of patients only. 47% of patients received ESA after start of dialysis. Before study, the mean weekly ESA dose in group C was statistically lower than in groups B and A (p < 0.001). At baseline visit, hemoglobin in group A patients was slightly lower than in group B and C patients (p = 0.025). In conclusion, in Central and Eastern European countries renal anemia therapy with ESA starts shortly before or after start of HD. This highlights important differences in standard care in Eastern Europe. However, paradoxically, due to the tight reimbursement policy we foresee the clinical implications of the TREAT trial for the chronic kidney disease population., (Copyright © 2011 S. Karger AG, Basel.)

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."

Unlabelled: 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., (Copyright © 2012 S. Karger AG, Basel.)

Background: Hemojuvelin (HJV) has recently emerged as one of a number of significant regulators of iron homeostasis and hepcidin expression. Recently, an immunoassay has been developed to measure circulating levels of soluble HJV (sHJV). The aim of this study was to measure serum hepcidin and sHJV levels in a chronic kidney disease (CKD) population., Methods: A total of 93 patients participated in the study (31 hemodialysis, 31 non-dialysis, 31 transplant recipients), and were matched for age and gender. Serum samples were taken for measurement of hepcidin-25 and sHJV, along with standard hematological, biochemical and inflammatory markers, and univariate/multivariate analyses were performed., Results: Serum sHJV levels were markedly elevated in the hemodialysis patients (2,619 ± 1,445 ng/ml) compared to the CKD (590 ± 344 ng/ml) and transplant recipients (870 ± 638 ng/ml) (p < 0.001), normal range 370-890 ng/ml. There was a strong correlation between serum ferritin and sHJV, which remained after adjustment for potential confounders (beta 0.92, p < 0.001). In the univariate analysis, sHJV levels correlated with serum hepcidin but this was not evident in the multivariate analysis. No associations were seen between sHJV and markers of inflammation or eGFR., Conclusions: sHJV is elevated in hemodialysis patients compared to non-dialysis CKD patients. There was no association between sHJV and eGFR (in the non-dialysis groups), suggesting that factors other than decreased renal clearance are responsible for the high sHJV levels. The strong association between sHJV and ferritin suggests an interdependent relationship, although further studies are required to elucidate the possible mechanism(s) for this., (Copyright © 2012 S. Karger AG, Basel.)

Background/aims: VAP-1 (vascular adhesion protein-1) is a copper-containing SSAO (semicarbazide sensitive amine oxidase) secreted by vascular smooth muscle cells, adipocytes, endothelial cells with functional monoamine oxidase activity. The oxidation process generates harmful products that may be involved in atherosclerosis and vascular damage. Elevation of SSAO activity is observed in atherosclerosis, diabetes mellitus and obesity. On the other hand, 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 levels and its correlations with endothelial injury markers and renalase in 50 kidney allograft recipients., Methods: Hemoglobin, urea, creatinine, rate were studied by standard laboratory method in the hospital central laboratory. We assessed markers of endothelial function/injury: vWF, thrombomodulin, ICAM, VCAM, CD40L, CD44, CD146, inflammation: hsCRP, and IL-6 and adipocytokines: leptin, adiponectin, visfatin, apelin with commercially available assays., Results: The mean serum VAP-1 in Tx was significantly higher comparing to the control group. In kidney transplant recipients VAP-1 correlated with BMI (r=0.39, p<0.01), CD44 (r=0.27, p<0.05), hsCRP (r=0.28, p<0.05), serum creatinine (r=0.29, p<0.05), eGFR (CKD-EPI formula r=-0.27, p<0.05, MDRD r=-0.27,p<0.05, Cockcroft-Gault r=-0.35,p<0.01), serum urea (r=0.27, p<0.05), CD146 (r=0.49, p<0.001), CD40L (r=0.26, p<0.06), and renalase (r=0.34, p<0.05). In multiple regression analysis VAP-1 was predicted 80% by serum creatinine (beta value 0.33, p=0.01), and CD146 (beta value 43, p=0.0005)., Conclusion: VAP-1, elevated in kidney transplant recipients, is predominantly dependent on endothelial damage and kidney function, which deteriorated with time after kidney transplantation., (Copyright © 2012 S. Karger AG, Basel.)

Background/aims: The aim of this study was to determine the correlation between renal function and 6-year mortality in patients with acute myocardial infarction (AMI), treated successfully with primary percutaneous coronary intervention (PCI), and to examine whether Cockcroft-Gault (C-G) formula or Modification of Diet in Renal Disease (MDRD) study equation or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation is the best predictor of very late mortality., Methods: A prospective cohort study with 6-year follow-up of a homogenous group of 193 patients, with ST-segment elevation AMI treated with successful primary PCI. Glomerular filtration rate (GFR) estimated by C-G formula, MDRD, and CKD-EPI equation were analyzed., Results: The patients with chronic kidney disease (CKD) had a much lower cumulative survival rate than those without it (p < 0.05). A larger area under the receiver-operating characteristic curve for death with respect to GFR for C-G formula was observed. In the multivariate analysis, only GFR ≥ 55 mL/min according to C-G formula was independently associated with lower mortality., Conclusion: CKD is associated with higher mortality after a successful primary PCI during a 6-year follow-up. C-G formula is better than MDRD and CKD-EPI equations at predicting mortality after AMI.

Copeptin is cosynthesized with vasopressin, also known as anti-diuretic hormone, with similar plasma levels. In the past 2 years, copeptin has been studied as a diagnostic and prognostic marker in infections and other diseases. In patients with decompensated heart failure, copeptin was an accurate prognostic marker for mortality. Cardiovascular disease is a major contributor to the mortality and morbidity in chronic kidney disease. Creation of an arteriovenous fistula (AVF) might contribute to the development or worsening of congestive heart failure (CHF). The aim of the study was to assess associations between copeptin, New York Heart Association (NYHA) class, and the location of the AVF in hemodialysis (HD) patients. The cross-sectional study was performed on a cohort of 93 clinically stable HD patients. Patients with proximal AVF tend to be older, with decreased renal residual function and increased NYHA functional class. These patients were also highly anemic, had more acidosis, and had increased high-sensitivity C-reactive protein along with increased copeptin and NT-proBNP levels. These changes were also associated with significant changes in all intra-cardiac dimensions, including right ventricle, both atria, and intraventricular septum and increase in end-systolic and end-diastolic left ventricular intra-cardiac dimensions. In multiple logistic regression analysis, the only associate of copeptin was NYHA functional class. Copeptin level in HD patients depends on cardiac function and it might be involved in the pathophysiology of cardiovascular disease in these patients. Proximal AVF creation might contribute to the development or worsening of CHF in HD patients.

Background: Heart transplantation is an established treatment for advanced heart failure. Heart transplant recipients experience a number of complications related to pharmacological immunosuppression and infections. Chronic kidney disease (CKD) is an important long-term complication of all forms of organ transplantation other than renal. It has been shown that a GFR <60ml/min is predictive of premature cardiovascular death. The aim of our study was to assess kidney function in relation to the type of immunosuppression regimen used., Material/methods: We analyzed 169 patients who underwent their first orthotopic heart transplant. The immunosuppressive regimen of prevalent patients consisted of tacrolimus (n=60), cyclosporine (n=109), in combination with mycophenolate mofetil (n=134), azathioprine (n=4), everolimus (n=28) or sirolimus (n=8). GFR was estimated using 3 formulae: CKD-EPI, MDRD and the Cockcroft-Gault. Complete blood count, urea, serum lipids, fasting glucose, creatinine, and NT-proBNP were also analyzed., Results: In patients treated with tacrolimus, we observed a higher eGFR (all formulae), a greater 24-hour creatinine clearance, and lower serum cholesterol, LDL-cholesterol and triglyceride values than in patients treated with cyclosporine. Patients treated with tacrolimus were younger than those treated with cyclosporine. However, the time elapsed after OHT was similar in both groups. The prevalence of CKD (eGFR <60 ml/min) in the tacrolimus-treated patients was 45%, whereas in the cyclosporine treated group it was 87% (p<0.01)., Conclusions: The prevalence of CKD is high in heart transplant recipients. Tacrolimus-based immunosuppression was associated with better kidney function and more favorable lipid profile. Evaluation of renal function is important in order to select the appropriate strategy by individually tailored therapy to achieve the best possible outcomes.

Background: Because creatinine is an unreliable variable describing kidney function, the search for a new and sensitive marker of kidney function is underway. Neutrophil gelatinase-associated lipocalin (NGAL) has been recently proven useful in the quantitation of chronic kidney disease (CKD). The aim of the study was to assess the prevalence of chronic kidney disease using estimated glomerular filtration rate (eGFR) and creatinine clearance according to different formulas and measurements of cystatin C and serum NGAL., Material/methods: One hundred sixty-nine prevalent heart transplant recipients in relation to age (younger and older than 65 years of age) were studied. Serum NGAL, cystatin C, creatinine, and eGFR were evaluated in all patients., Results: Elderly heart recipients had significantly higher cystatin C and serum NGAL and lower eGFR than their younger counterparts, despite not having a statistically different serum creatinine. In the group of 27 elderly recipients, according to the Cockcroft-Gault formula, 22 patients had stage 3 CKD and 4 had stage 4 CKD; according to the Modification of Diet in Renal Disease (MDRD) Study formula, 5 had stage 2 CKD, 15 had stage 3 CKD, and 7 had stage 4 CKD; according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, 5 had stage 2 CKD, 15 had stage 3 CKD, and 7 had stage 4 CKD; and according to the calculation of 24-hour creatinine clearance, 5 had stage 2 CKD, 16 had stage 3 CKD, and 6 had stage 4 CKD., Conclusions: The prevalence of CKD in the elderly population was as high as 81% (MDRD, CKD-EPI, creatinine clearance) to 100% (Cockcroft-Gault formula), whereas in the younger population of heart transplant recipients the prevalence of CKD ranged from 56.3% to 77.5%. Serum NGAL could be a sensitive marker of kidney function, particularly in elderly patients.

Background: Kidney disease and cardiovascular disease seem to be lethally synergistic and both are approaching the epidemic level. A reduced glomerular filtration rate is associated with increased mortality risk in patients with heart failure. Many patients with congestive heart failure are anemic. Anemia is very often associated with chronic kidney disease., Objectives: To assess--in relation to New York Heart Association class--the prevalence of anemia and chronic kidney disease in patients with normal serum creatinine in a cohort of 526 consecutive patients with coronary artery disease undergoing percutaneous coronary interventions., Methods: GFR was estimated using the simplified MDRD formula, the Cockcroft-Gault formula, the Jeliffe and the novel CKD-EPI formula., Results: According to the WHO definition the prevalence of anemia in our study was 21%. We observed a progressive decline in GFR and hemoglobin concentration together with a rise in NYHA class. Significant correlations were observed between eGFR and systolic blood pressure, diastolic blood pressure, age, NYHA class, complications of PCI, including bleeding, and major adverse cardiac events., Conclusions: The prevalence of anemia and chronic kidney disease is high in patients undergoing PCI despite normal serum creatinine, particularly in higher NYHA class. Lower eGFR and hemoglobin are associated with more complications, including bleeding after PCI and higher prevalence of major adverse cardiac events. In patients with risk factors for cardiovascular disease, GFR should be estimated since renal dysfunction and subsequent anemia are important risk factors for cardiovascular morbidity and mortality.

Aim: Visfatin is an adipocytokine that has recently generated much interest. The aim of the study was to assess visfatin in correlation with markers of endothelial damage and inflammation in haemodialyzed and peritoneally dialyzed patients., Methods: Visfatin, leptin, apelin and adiponectin, markers of coagulation (thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2)), fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1)), endothelial function/injury (Von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), CD146) and inflammation (high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6) were assessed., Results: Triglycerides, hsCRP, creatinine, IL-6, TNF-alpha, vWF, F1+2, TAT, thrombomodulin, ICAM, VCAM, CD146, PAI-1, leptin, adiponectin and visfatin were elevated in dialyzed patients over controls. Visfatin correlated significantly, in univariate analysis, in haemodialyzed patients with markers of endothelial damage/inflammation (CD146, ICAM, IL-6), other adipocytokines, Kt/V and dialysis vintage, and tended to correlate with hsCRP. In peritoneally dialyzed patients, visfatin correlated significantly with haemoglobin, and markers of endothelial damage. In the healthy volunteers visfatin correlated significantly with ICAM, creatinine and IL-6. In multiple regression analysis in HD patients visfatin was only independently related to Kt/V, dialysis vintage and IL-6., Conclusion: Elevated visfatin related to markers of inflammation might represent a novel link between inflammation and adipocytokines in dialyzed patients. Time on dialyses and dialysis adequacy may influence visfatin in dialyzed patients due to the decreased clearance of visfatin.

Background: Heart transplantation is an established treatment for advanced heart failure. However, chronic kidney disease (CKD) is an important long-term complication of all forms of organ transplantation other than renal. It has been shown that a GFR <60 ml/min is predictive of premature cardiovascular death., Material/methods: The aim of this study was to assess the prevalence of kidney dysfunction in heart transplant recipients using a new CKD-EPI formula in a cohort of 169 prevalent patients (mean age 53.30+/-13.80 years)., Results: Mean serum creatinine in this population was 1.71+/-1.10 mg/dl, Serum creatinine was normal (<1.4 mg/dL in males and <1.2 mg/dL in females) in 45.4% of the patients. According to the Cockcroft-Gault formula, stage 2 CKD (i.e.GFR 60-89 ml/min) was demonstrated in 79 patients (46.75%), stage 3 CKD (i.e. GFR 30-59 ml/min) in 49 patients (29.00%) and stage 4 CKD (i.e. GFR 15-29 ml/min) in 15 patients (8.88%). According to MDRD formula stage 2 CKD was found in 36 patients (21.30%), stage 3 CKD was found in 79 patients (46.75%) and stage 4 in 27 patients (15.98%). According to new CKD-EPI formula, stage 2 CKD was found in 35 patients (20.71%), stage 3 CKD in 79 patients (46.75%) and stage 4 in 28 patients (16.57%). According to the creatinine clearance stage 2 CKD was found in 61 patients (36.09%), stage 3 CKD in 63 patients (37.28%) and stage 4 in 19 (11.24%) patients. Clinically significant CKD (GFR <60 ml/min) was found in 37.88-63.91% depending on the formula used to estimate the GFR. Normal kidney function was found in 27 patients (15.98%) according to MDRD formula, in 27 patients (15.98%) according to new CKD-EPI formula, in 26 patients (15.38%) according Cockcroft-Gault formula and 26 patients (15.38%) on the basis of 24-hours creatinine clearance., Conclusions: We conclude that the prevalence of CKD is high in heart transplant recipients. Evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. New CKD-EPI formula seems to more accurate in assessment kidney function that previously used, however, it merits further studied and validation against gold standard of isotope GFR measurement.

Chronic kidney disease developed after non renal solid organ transplantation in a significant issue. Evaluation of kidney function starting form a complete history and physical examination, then an accurate measurement of renal function and a urinalysis, followed by kidney imaging study should be performed prior to transplantation. Moreover, probability of reversibility of kidney dysfunction and the risk of progression to end stage renal disease should be assessed. During peri- and postoperative period hypotensive episodes should be avoided or at least minimized. Good blood pressure control (however, no guidelines for target blood pressure values for non solid organ transplants are available) as well as tight control of diabetes and hyperlipidemia should be implemented. Proteinuria, if present, should be attenuated by the use of therapeutic modalities (RAS blockade) to prevent or delay the progression of renal failure. The ability to identify CKD may allow early implementation of treatments that could arrest or delay the progression of renal damage, enable effective treatment of its complications, and reduce the risk of drug-induced nephrotoxicity. Kidney function should be monitored in nonrenal solid organ transplant recipients as an important risk factor comparable with diabetes for cardiovascular mortality and morbidity. In presence of existing nephron sparing immunosuppressive regimens, early detection of deteriorating kidney function gives the opportunity to tailor the treatment. A multidisciplinary approach for these patients including also a nephrologist should be considered.

The value of neutrophil gelatinase-associated lipocalin (NGAL) as a novel marker for early detection of acute renal failure has been highlighted recently. The aim of this study was to assess whether serum NGAL correlates with kidney function in kidney allograft recipients. Serum NGAL, creatinine, and estimated glomerular filtration rate (GFR) were evaluated in 100 kidney allograft recipients on triple therapy: calcineurin inhibitor, mycophenolate mofetil or azathioprine, prednisone and healthy volunteers. Kidney transplant recipients had significantly higher NGAL than the control group. Serum NGAL in univariate analysis was strongly correlated with serum creatinine (r = 0.78). Estimated GFR (r = -0.69), on the other hand, was moderately correlated with white blood cell count (r = 0.43) and only weakly with other parameters. In multiple regression analysis, the best predictor of serum NGAL was eGFR (beta -0.69), with other predictors being white blood cell count (beta 0.25) and high sensitivity C-reactive protein (hsCRP) (beta 0.23) explaining 82% of NGAL concentration. Even a successful kidney transplantation is associated with kidney injury as reflected by elevated serum NGAL and lowered eGFR. Therefore, NGAL needs to be investigated as a potential early marker for impaired kidney function/kidney injury, especially in patients with other risk factor for kidney damage, i.e., hypertension or diabetes.

Aim: Hypertension is one of the risk factors for cardiovascular diseases. The kidneys could be a victim and/or culprit of hypertension. Recently, the value of neutrophil gelatinase-associated lipocalin (NGAL) was highlighted as a novel marker for early detection of acute renal damage. Therefore, the aim of the study was to assess whether hypertension could affect NGAL and cystatin C levels in patients with normal serum creatinine (lower than 1.5 mg/dL in males and 1.2 mg/dL in females) and stable coronary artery disease., Methods: Serum, urinary NGAL, cystatin C and estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease study (MDRD) and Cockcroft-Gault formulas) were evaluated in hypertensive, normotensive patients with stable coronary heart disease and healthy volunteers., Results: Normotensives had significantly lower NGAL than hypertensives. Serum cystatin C was significantly lower in normotensives than in hypertensives. Urinary NGAL did not differ significantly between these groups. Despite similar serum creatinine levels, eGFR (MDRD and Cockcroft-Gault formulas) was significantly higher in normotensives than in hypertensives. Serum NGAL was related, in univariate analysis, to serum creatinine, urea, urinary NGAL, haemoglobin, haematocrit, duration of hypertension, age, eGFR by MDRD and Cockcroft-Gault, and cystatin C., Conclusion: Hypertension is associated with kidney injury as reflected by elevated serum NGAL and cystatin C. It is noteworthy that despite normal serum creatinine, eGFR is relatively low suggesting impaired renal function. Therefore, NGAL needs to be investigated as a potential early marker for impaired kidney function/kidney injury, especially in patients with another risk factor for kidney damage, namely coronary artery disease.

Aim: Resistin is an adipocytokine that recently generated much interest. Because of the fact that inflammation, endothelial cell damage or injury is invariably associated with such clinical conditions as thrombosis, atherosclerosis and their major clinical consequences, that is, cardiovascular disease and resistin play a role in linking inflammation and cardiovascular disease, the aim of the study was to assess resistin in correlation with markers of inflammation, endothelial cell injury and residual renal function in haemodialysed (HD) patients., Methods: We assessed resistin, markers of coagulation: thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2; fibrinolysis: tPA, plasminogen activator inhibitor type 1, plasmin-antiplasmin complexes (PAP); endothelial function/injury: von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM); inflammation: high sensitivity C-reactive protein (hsCRP), tumour necrosis factor alpha and interleukin-6 (IL-6)., Results: Healthy volunteers and HD patients did not differ significantly regarding age, leucocyte count, serum iron, aspartate and alanine aminotransferases activities, calcium, cholesterol, tPA concentration. Triglycerides, CRP (assessed by high sensitivity method), phosphate, urea, creatinine, IL-6, tumour necrosis factor alpha, vWF, prothrombin fragments 1+2, TAT, PAP, thrombomodulin, ICAM, plasminogen activator inhibitor type 1 and resistin, were elevated in HD patients when compared with the control group. Serum albumin, total protein, haemoglobin and haematocrit were significantly lower in HD patients when compared with the control group. In HD patients with hsCRP 0e; 6 mg/L, resistin, IL-6, vWF and F1+2 were significantly higher, whereas tPA was significantly lower than in patients with hsCRP<6 mg/L. Moreover, HD patients with residual renal function have significantly lower resistin when compared with patients without it. Resistin was significantly higher in diabetics. In HD patients, resistin correlated significantly, in univariate analysis, with calcium, phosphate, PTH, TIBC, vWF residual renal function, urea, hsCRP, IL-6 and tended to correlate with tPA and ferritin. In the healthy volunteers, resistin was related to IL-6 and hsCRP. In multiple regression analysis, resistin was independently related to hsCRP, IL-6, residual renal function in HD patients., Conclusion: Elevated resistin related to markers of inflammation may represent a novel link between inflammation and adipocytokines in HD patients. Impaired renal function and inflammation are responsible for elevated resistin in HD patients.

Hypothesis: The recent Dialysis Outcome Quality Initiative publication on the evaluation, classification and stratification of chronic kidney disease (CKD) states that individuals with a reduced glomerular filtration rate (GFR) is at greater risk for cardiovascular diseases and cardiac deaths., Aim: To determine the prevalence of kidney dysfunction in a cohort of 1390 patients with and without diabetes with normal serum creatinine undergoing percutaneous coronary intervention., Methods: Kidney function was estimated using simplified MDRD, Cockcroft-Gault and Jeliffe formulas., Results: Normal serum creatinine was observed in 93% patients. Mean estimated GFR in 1068 non-diabetic patients was significantly higher than in 322 diabetic patients (all formulas). Diabetic females had significantly lower creatinine and estimated GFR, higher high-density lipoprotein and platelet count than diabetic males. A very high prevalence of CKD up to 77% was found in studied diabetic patients. Clinically significant CKD (as defined by GFR < 60 mL/min) was found in 13.0-33.8% patients depending on the formula used to estimate GFR., Conclusion: The prevalence of CKD (stages 2-3) is high in diabetic patients undergoing percutaneous coronary intervention despite normal creatinine. The risk of contrast nephropathy with worse outcomes is enhanced in these patients, particularly in elderly and females. Evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk.

Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Hepcidin could also act as an indicator of functional iron deficiency in these patients. Cross-sectional study was performed to assess hepcidin correlations with renal function, iron status, and hsCRP in patients with chronic renal failure on conservative treatment, on hemodialyses, and in kidney transplant recipients. Iron status, complete blood count, creatinine, albumin, lipids were assessed using standard laboratory methods. GFR was estimated using MDRD formula. Hepcidin and high sensitivity CRP were measured using commercially available kits. Ferritin and hepcidin were higher in hemodialyzed patients, kidney transplant recipients, and patients with chronic renal failure over controls. In patients with chronic renal failure, hepcidin correlated significantly with total protein, albumin, creatinine, and eGRF. In kidney transplant recipients, hepcidin correlated significantly in univariate analysis, with total protein, ferritin, time after transplantation, creatinine, eGRF and tended to correlate with cholesterol. In hemodialyzed patients hepcidin, correlated significantly with triglycerides, albumin, creatinine, urea, residual renal function, and hsCRP. In healthy volunteers, hepcidin was related to triglycerides and ferritin. Multiple regression analysis in hemodialyzed patients showed that hepcidin was independently related to creatinine, triglycerides, and residual renal function. Multiple regression analysis in kidney transplant recipients showed that hepcidin was independently related only to GFR and ferritin. Elevated hepcidin in all groups of patients studied may be due to low grade inflammation, frequently encountered in this population and mainly to impaired renal function., ((c) 2006 Wiley-Liss, Inc.)

Background: Renal function affects thyroid function and adipocytokines in many ways. We aimed to assess the adipocytokines adiponectin and leptin in relation to thyroid function in patients with chronic renal failure treated conservatively, in haemodialysed patients and in kidney allograft recipients., Methods: The study was performed on 33 patients with chronic renal failure, 64 haemodialysed patients, 54 kidney allograft recipients and 38 healthy volunteers. Thyroid volume was estimated sonographically, thyroid hormones were determined by Micropartide Enzyme Immunoassay (MEIA), and serum adiponectin and leptin were assessed by radioimmunoassay., Results: Serum thyroid-stimulating hormone (TSH), free T4 and free T3 were within the normal range. Adiponectin correlated significantly with free T3, haematocrit, haemoglobin, platelet count, body mass index (BMI) and urea in kidney allograft recipients. In haemodialysed patients, adiponectin correlated with free T4 and TSH, whereas leptin correlated with free T3. Multiple regression analysis showed that adiponectin was independently related only to the serum concentration of free T3 and urea in kidney transplant recipients and to free T4 and adequacy of dialysis in haemodialysed patients. In univariate analysis in patients with chronic renal failure, adiponectin correlated with free T3 and platelet count, and in healthy volunteers adiponectin correlated only with free T3 and triglycerides, and leptin correlated with BMI., Conclusions: We described novel relationships between adiponectin and thyroid hormones in patients with kidney diseases. However, possible pre-existing thyroid dysfunction prior to transplantation (during dialysis therapy) and immunosuppression after transplantation make all these findings relatively complex. Therefore, the relationships between adiponectin and the thyroid axis in patients with chronic renal failure, in haemodialysed subjects or in kidney transplant recipients merit additional studies.

Cardiovascular disease (CVD) is the main cause of mortality and morbidity among kidney transplant recipients (Tx). Intima-media thickness (IMT) of the common carotid artery is related to CVD. Hemostatic disturbances may contribute to the CVD pathogenesis in Tx. The aim of the study was to evaluate some hemostatic factors in Tx with and without coronary artery disease (CAD) and their correlations with IMT. Patients with CAD were significantly older, with thicker IMT, lower plasmin-antiplasmin complexes (PAP), higher fibrinogen, cholesterol, triglycerides, Thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and activity, prolonged euglobulin clot lysis time when compared to those without CAD. Kidney transplant recipients have higher mean blood pressure, serum lipids, fibrinogen, TAFI antigen, TAFI activity, markers of coagulation and fibrinolysis, thicker IMT and lower PAP relative to healthy volunteers. In univariate analysis, IMT correlated significantly with age, time on dialysis prior to transplantation, PAP, fibrinogen, hematocrit, body mass index (BMI). Multiple regression analysis showed that only age, hematocrit, PAP, and time on dialysis prior to transplantation were positive independent predictors of IMT. Hypofibrinolysis may contribute to the arterial remodeling in Tx. Dialysis therapy before transplantation makes detrimental changes in arterial vasculature.

Adiponectin has antiatherogenic properties and attenuates endothelial inflammatory responses. CD146 is a novel cell adhesion molecule localized at the endothelial junction. In renal failure, endothelial dysfunction and atherosclerosis are almost universal. We studied possible correlations between adiponectin, CD146, and other markers of endothelial cell injury in patients with chronic renal failure (CRF) on conservative treatment and patients with and without diabetic nephropathy maintained on chronic ambulatory peritoneal dialysis (CAPD). We assessed adiponectin, tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor (PAI-1), thrombin-activatable fibrinolysis inhibitor, and endothelial function/injury markers: von Willebrand factor, thrombomodulin, vascular cell adhesion molecule (VCAM), intercellular adhesion molecule, and CD146. Adiponectin was elevated in patients with CRF and on CAPD. It correlated significantly, with PAI-1, thrombin-activatable fibrinolysis inhibitor, intercellular adhesion molecule, VCAM, and CD146 in nondiabetics on CAPD. In diabetics, CAPD adiponectin correlated positively with C146 and VCAM and negatively with PAI and TFPI. In multivariate regression analysis, only CD146 remained a positive predictor of adiponectin in all CAPD patients. In CRF, adiponectin correlated with CD146. In healthy volunteers, adiponectin correlated with TFPI and CD146. Elevated adiponectin related to CD146 may be the expression of a counterregulatory response aimed at mitigating the consequences in endothelial damage and increased cardiovascular risk in renal failure.