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Diabetic nephropathy is currently the leading cause of end-stage kidney disease. The present methods of assessing diabetes control, such as glycated hemoglobin or self-monitoring of blood glucose, have limitations. Over the past decade, the field of continuous glucose monitoring has been greatly improved and expanded. This review examines the use of continuous glucose monitoring in people with end-stage kidney disease treated with hemodialysis (HD), peritoneal dialysis (PD), or kidney transplantation. We assessed the use of both real-time continuous glucose monitoring and flash glucose monitoring technology in terms of hypoglycemia detection, glycemic variability, and efficacy, defined as an improvement in clinical outcomes and diabetes control. Overall, the use of continuous glucose monitoring in individuals with end-stage kidney disease may improve glycemic control and detection of hypoglycemia. However, most of the published studies were observational with no control group. Moreover, not all studies used the same assessment parameters. There are very few studies involving subjects on peritoneal dialysis. The small number of studies with limited numbers of participants, short follow-up period, and small number of manufacturers of continuous glucose monitoring systems are limitations of the review. More studies need to be performed to obtain more reliable results., (© 2023. The Author(s).)

Recent studies have suggested benefits for time-dependent dialysate bicarbonate concentrations (D bic ) during hemodialysis (HD). In this clinical trial, we compared for the first time in the same HD patients the effects of time-dependent changes with constant D bic on acid-base and uremic solute kinetics. Blood acid-base and uremic solute concentration were measured in twenty chronic HD patients during 4-h treatments with A) constant D bic of 35 mmol/L; B) D bic of 35 mmol/L then 30 mmol/L; and C) D bic of 30 mmol/L then 35 mmol/L (change of D bic after two hours during Treatments B and C). Arterial blood samples were obtained predialysis, every hour during HD and one hour after HD, during second and third treatments of the week with each D bic concentration profile. Blood bicarbonate concentration (blood [HCO 3 ]) during Treatment C was lower only during the first three HD hours than in Treatment A. Overall blood [HCO 3 ] was reduced during Treatment B in comparison to Treatment A at each time points. We conclude that a single change D bic in the middle of HD can alter the rate of change in blood [HCO 3 ] and pH during HD; time-dependent D bic had no influence on uremic solute kinetics., (© 2024. The Author(s).)

Transplantation offers cure for some haematological cancers, end-stage organ failure, but at the cost of long-term complications. Renal transplantation is the best-known kidney replacement therapy and it can prolong end-stage renal disease patient lives for decades. However, patients after renal transplantation are at a higher risk of developing different complications connected not only with surgical procedure but also with immunosuppressive treatment, chronic kidney disease progression and rejection processes. Various blood disorders can develop in post-transplant patients ranging from relatively benign anaemia through cytopenias to therapy-related myelodysplasia and acute myeloid leukaemia (AML) and post-transplant lymphoproliferative disorders followed by a rare and fatal condition of thrombotic microangiopathy and haemophagocytic syndrome. So far literature mainly focused on the post-transplant lymphoproliferative disease. In this review, a variety of haematological problems after transplantation ranging from rare disorders such as myelodysplasia and AML to relatively common conditions such as anaemia and iron deficiency are presented with up-to-date diagnosis and management., (© The Author(s) 2020. Published by Oxford University Press on behalf of the ERA.)

Introduction: Sirtuin1 (SIRT1) acts as an anti-aging protein due to anti-apoptotic, anti-oxidative and anti-inflammatory effect and is implicated in several diseases including diabetes or cardiovascular problems. SIRT1 renal overexpression indicates oxidative stress. Similarly, αKlotho was primarily exposed as anti-aging factor. It is primary produced in kidney. It's deficiency is associated with progression of chronic kidney disease and heart disorders., Purpose: The aim of the study was to assess the serum concentration of sirtuin1 and αKlotho in hemodialysis (HD) patients compared to healthy volunteers in regard to age, blood pressure control, residual kidney function (RKF), diabetes, cardiovascular disease, dialysis vintage and type of dialyzer., Patients and Methods: The serum level of SIRT1 and αKlotho was evaluated using ELISA tests in 103 HD patients, median age 67 years and in 21 volunteers. Blood pressure, RRF, echocardiography and dialysis parameters were assessed. HD group was divided according to the presence/absence of RKF., Results: The serum SIRT1 level was higher (28.4 vs 2.71ng/mL, p<0.0001) and αKlotho was lower (433.9 vs 756.6pg/mL, p<0.0001) in HD then in control group. αKlotho was lower in those without RKF (387.2 vs 486.2pg/mL, p=0.028). SIRT1 positively correlated with hemodialysis vintage. αKlotho negatively correlated with left ventricular posterior wall thickness. There was no significant relationship between SIRT1 and αKlotho level and age, blood pressure control, type of dialyzer, Kt/V and diabetes. Multivariate analysis revealed association of SIRT1 with ejection fraction (B -0.72; p=0.32)., Conclusion: Elevated SIRT1 and lower αKlotho concentration are associated with impaired kidney function. The decrease in levels of αKlotho may also indicate heart hypertrophy in hemodialysis patients. The role of anti-aging proteins, particularly SIRT1 as biomarkers/predictors of oxidative stress, inflammation and cardiovascular diseases need further examination., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Zbroch et al.)

The epidemic with the new SARS-CoV-2 virus poses a serious threat to patients treated with renal replacement therapy. Besides clinical risk factors (such as numerous comorbidities, immune disorders), dialysis patients are additionally exposed to the virus through regular stays for several hours in a dialysis center and ambulance journeys. In such an epidemiological situation, it seems that peritoneal dialysis and home hemodialysis are good alternatives for treatment. Currently available telemedicine and medical technologies allow for effective renal replacement therapy also outside dialysis centers. Thanks to this, it is possible to limit the stay of patients in a medical facility to clinically justified situations. For this reason, increasing the number of patients treated with peritoneal dialysis, which is carried out at home and without contact with medical personnel, seems to be a good solution. Enabling patients to undergo home hemodialysis treatment, nowadays unavailable in Poland and establishing it as a guaranteed benefit in the health care system will enable renal replacement therapy to be adapted to the clinical condition and the need for isolation.

Patients on long-term hemodialysis are at very high risk for cardiovascular disease but are usually excluded from clinical trials conducted in the general population or in at-risk populations. There are no universally agreed cardiovascular outcomes for trials conducted specifically in the hemodialysis population. In this review, we highlight that trials reporting cardiovascular outcomes in hemodialysis patients are usually of short duration (median 3 to 6 months) and are small (59% of trials have <100 participants). Overall, the cardiovascular outcomes are very heterogeneous and may not reflect outcomes that are meaningful to patients and clinicians in supporting decision making, as they are often surrogates of uncertain clinical importance. Composite outcomes used in different trials rarely share the same components. In a field in which a single trial is often insufficiently powered to fully assess the clinical and economic impact of interventions, differences in outcome reporting across trials make the task of meta-analysis and interpretation of all the available evidence challenging. Core outcome sets are now being established across many specialties in health care to prevent these problems. Through the global Standardized Outcomes in Nephrology-Hemodialysis initiative, cardiovascular disease was identified as a critically important core domain to be reported in all trials in hemodialysis. Informed by the current state of reporting of cardiovascular outcomes, a core outcome measure for cardiovascular disease is currently being established with involvement of patients, caregivers, and health professionals. Consistent reporting of cardiovascular outcomes that are critically important to hemodialysis patients and clinicians will strengthen the evidence base to inform care in this very high-risk population., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Traditional anticoagulants used in intermittent hemodialysis (HD) are unfractionated heparin (UFH) and increasingly low molecular weight heparins (LMWHs). Repeated and prolonged exposure to UFH and/or LMWHs may further disturb hemostasis in uremic patients. Vascular adhesion protein-1 (VAP-1) is secreted by vascular smooth muscle cells, adipocytes and endothelial cells with functional monoamine oxidase activity and is elevated in atherosclerosis, diabetes mellitus and obesity. The aim of this study was to assess the effects of UFH and LMWHs on VAP-1 concentration in HD patients. The effects on single HD session on VAP-1 were also evaluated as well as VAP-1 levels in regard to type of renal replacement therapy., Methods: We studied 82 hemodialyzed patients (mean age 63 years, dialysis vintage 59 months) and 17 patients treated by means of hemodiafiltration (HDF) (mean age 59 years, HD vintage 84 months, HDF 7 months). Patients were anticoagulated with enoxaparin (n = 46), dalteparin (n = 10), nadroparin (n = 6) or UFH (n = 20) during their HD sessions. VAP-1 was assessed using kits from BioVendor, Modrice, Czech Republic., Results: Patients on HDF had significantly lower VAP-1 when compared with HD patients. We found that VAP-1 concentration in patients dialyzed by using LMWH or UFH was similar. There was no effect on HD session on VAP-1 concentration. Diabetic patients had higher serum VAP-1 than non-diabetic., Conclusions: HDF is associated with lower VAP-1 levels indicating less pronounced endothelial cell injury than hemodialysis. Type of heparin seems to have no effect on VAP-1 levels in hemodialyzed patients. However, the cross-sectional but not prospective design is a limitation of this study.

Introduction: Anemia has been remained one of the most characteristic and visible manifestations of chronic renal failure. Correction of anemia requires two main treatment strategies: increased stimulation of erythropoiesis, and maintenance of an adequate iron supply to the bone marrow., Areas Covered: Erythropoiesis activating agents became a mainstay in the treatment of renal anemia for more than 25 years. Recently, there have been several attempts to introduce new drugs to stimulate erythropoiesis or affect the hepcidin-ferroportin pathway. Orally available hypoxia-inducible factor (HIF) stabilizing compounds are attractive alternatives. They not only increase hemoglobin, but also suppress hepcidin production and improve iron availability. Novel iron preparations, may also help to ameliorate anemia, with acceptable safety profile and other beneficial properties such a phosphate binding., Expert Opinion: One should be aware of potential risks and benefits of novel sophisticated therapies and their role in the management of renal anemia remain to be established. In particular HIF stabilizers needs to be proven safe, or even safer than ESAs, in large long-term safety studies testing hard end points, due its ubiquitous nature and the regulation of variety of biological processes potentially leading to unexpected side effects. Besides safety, cost-effectiveness appears the major issue in the modern world, including nephrology.

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.

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.

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.)

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.)

Recently, a new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was presented as a better alternative to the modification of diet in renal disease (MDRD) formula for GFR estimation (eGFR) in patients with relatively well-preserved kidney function. The main objective of our study was to compare the eGFR results arrived by the new CKD-EPI to the older MDRD equation in antiretroviral (ARV)-naive and ARV-treated HIV-1-infected patients. The study was performed in 287 adult HIV-1-infected patients and was an evaluation comparing eGFR results based on age, gender, race, and serum creatinine. The biggest difference in estimated glomerular filtration rate (eGFR) measured by the two formulas was seen in ARV-naive men with well-preserved kidney function (p = 0.001). Moreover, we found a significant negative correlation between mean difference in eGFR measured by the two equations and the age of the studied subjects (r = -0.37, p < 0.001). No correlation was observed between mean difference in eGFR and HIV viral load (r = -0.15, p = 0.2). Independent of the equation used, a significant decrease of eGFR in ARV-treated in comparison to ARV-untreated HIV-1-infected patients was seen (p < 0.001). In conclusion, in HIV-1-infected subjects, especially in ARV-naive men with well-preserved kidney function, eGFR measured by MDRD and CKD-EPI formulas varies strongly following the method used. Such discrepancies may be important in everyday clinical practice and must be confirmed by additional studies using GFR measured with a reference method.

Apelin, a newly discovered adipocytokine, is produced by white adipose tissue and also expressed in kidney and heart. Increasing evidence suggests a role for apelin in the pathology of the cardiovascular system. It was demonstrated that apelin may contribute to the pathophysiology of human chronic heart failure. Apelin locates at the endothelium-a site of key functional importance in the kidney, and apelin has been shown to increase cardiac output. Cardiovascular disease is a major contributor to the mortality and morbidity of patients with chronic renal failure. We previously found that apelin was significantly lower in dialyzed patients with coronary artery disease and its level was predicted by cardiac function. Creation of a-v fistula might contribute to the development or worsening of chronic heart failure. The aim of this study was to assess associations between apelin, other adipocytokines, NYHA class and location of a-v fistula in hemodialyzed patients. This cross-sectional study was performed on a cohort of one hundred, clinically stable hemodialyzed patients. We investigated plasma apelin as well other adipocytokines: resistin, visfatin and von Willebrand factor (vWF)-a marker of endothelial cell injury. In patients with a-v fistula on the forearm (n = 77), apelin was significantly higher than in patients with a-v fistula on the arm (n = 23) (56.79 ± 23.56 vs. 43.12 ± 23.19 pg/ml). Patients with forearm a-v fistula had lower left ventricular internal end-diastolic dimension (LVIDd) (P < 0.05), left ventricular internal end-systolic dimension (LVISd) (P < 0.05), NYHA class (P < 0.05), hsCRP (P < 0.01), plasma vWF (P < 0.01), and plasma resistin (P < 0.05), whereas the ejection fraction was higher than in patients with arm a-v fistula (P < 0.05), as well as hemoglobin (P < 0.05), hematocrit (P < 0.01), prevalence of diabetes (n < 0.05), prevalence of coronary heart disease (P < 0.05), serum pH (P < 0.05), serum bicarbonate (P < 0.05). Apelin was related to echocardiographic parameters, presence of diabetes, coronary artery disease, chronic heart failure, NYHA class and serum lipids (total cholesterol, LDL, triglycerides), hsCRP, vWF, residual renal function, and Kt/V. In multiple logistic regression analysis, apelin was significantly associated with ejection fraction (beta value was -0.51, P = 0.007), the presence of diabetes (beta value 0.39, P = 0.049), a-v fistula arm location (beta value 0.42, P = 0.047). Multiple adjusted r (2) for variables in the equation = 0.45, F = 1.75, P = 0.04, SE of estimate = 20.85. Apelin level in dialyzed patients is predicted by cardiac function, presence of diabetes and location of a-v fistula. Apelin might be involved in the pathophysiology of cardiovascular disease in chronic renal failure. The arm location of the fistula might contribute to the development or the worsening of chronic heart failure in hemodialyzed patients.

Background/aims: To assess the impact of diabetes mellitus (DM) on clinical outcome in patients with end-stage renal disease (ESRD) on a 3-year follow-up., Methods: 58 ESRD patients were divided into 2 groups according to the presence of DM. We analyzed following end points: death, cardiac arrest, myocardial infarction, stroke, hospitalizations due to cardiovascular causes, revascularization, and combined end point., Results: Among diabetics, 14 (77.8%) had significant atherosclerotic changes, in the group without DM only 8 (38.1%), p = 0.01. In the group without DM, 14 (46.7%) patients reached combined end point, while in the group with DM 16 (53.3%) patients, p = 0.0013. There were no statistical differences in mortality (p = 0.423)., Conclusion: Survival of hemodialyzed diabetic patients is not inferior to nondiabetics; however, morbidity is significantly higher due to adverse cardiac events., (Copyright © 2011 S. Karger AG, Basel.)

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.

Background: Myocardial ischaemia in patients with end-stage renal disease (ESRD) develops both due to the epicardial coronary artery stenosis and to the microvascular injury. We aimed to evaluate coronary blood flow in ESRD patients by means of the thrombolysis in myocardial infarction (TIMI) frame count method (TFC). In patients with ESRD, implementation of the TFC as a marker of the coronary flow abnormalities have not been previously investigated., Methods: Thirty-nine ESRD patients on regular dialysis underwent elective coronary angiography. Coronary artery stenosis >75% was defined as significant. TFC for the three main coronary vessels was calculated. Higher TFC values reflected slower flow., Results: In 19 patients (49%), significant epicardial coronary artery disease was found. Distribution of the TFC for the three main coronary arteries reflected prevalence for higher TFC values. Mean corrected TFC for the left anterior descending artery (LAD) was 34.7 +/- 16, for the circumflex artery (Cx) 41.5 +/- 25 and for the right coronary artery (RCA) 30.9 +/- 18 frames. For the three main coronary vessels, there were no statistically significant differences between the mean TFC values according to the presence or absence of the severe coronary artery stenoses on angiography (LAD: 30.2 +/- 12 vs 36.3 +/- 18; Cx: 41.5 +/- 20 vs 41.5 +/- 27; RCA: 34.9 +/- 16 vs 30.0 +/- 19, respectively)., Conclusions: Our results demonstrate for the first time the reduction in blood flow velocity, assessed with TFC method, in the coronary arteries of ESRD patients. This phenomenon was observed regardless of the presence of the significant epicardial coronary artery stenosis. Therefore, TFC cannot be applied as a marker of significant coronary artery stenosis in ESRD population.

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.

Aim: The aim of this study was to assess the prognostic significance of myocardial contrast echocardiography (MCE) in patients with end-stage renal disease (ESRD) on a 3-year follow-up and to compare the value of MCE with demographic, clinical, and laboratory parameters., Methods: Fifty-eight ESRD patients on regular dialysis were prospectively screened for coronary artery disease (CAD) using perfusion assessment on real-time MCE. We analyzed the following end points during the 3-year follow-up: death, cardiovascular complications, and combined end point, which consisted of adverse cardiac events mentioned above. All features were compared between the two groups with and without perfusion disturbances on MCE., Results: No adverse events related to MCE administration have been observed. Twenty-seven (47%) patients with ESRD demonstrated perfusion defects on MCE. The patients with perfusion defects on MCE comparison with those without perfusion disturbances were older (p = 0.008) and had lower ejection fraction (EF) (p = 0.0001) and higher wall motion index (WMSI) (p = 0.0001). After the 3-year follow-up, the incidence of death (p = 0.00018), cardiovascular end points, revascularizations [both percutaneous coronary intervention (PCI) and coronary artery bypass grafts (CABG) p = 0.0016 and p = 0.004, respectively], and composite end point (p = 0.0015) was significantly higher in patients with perfusion defect on MCE., Conclusions: In patients with ESRD, MCE appears to be a safe and useful tool for risk stratification. MCE facilitates decision for coronary angiography.

Hepcidin is the key regulator of iron metabolism. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietic-stimulating agents. The present study was aimed to assess possible relation between hepcidin and erythropoietin therapy, with particular attention being paid to erythropoietin-hyporesponsiveness in hemodialyzed patients. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Germany (ELISA method) and Bachem, UK (RIA method). TNFalpha and IL-6 were studied using kits from and R&D (Abington, UK), and hsCRP was studied using kits from American Diagnostica, USA. Hyporesponsive patients to erythropoietin therapy had significantly lower serum albumin, cholesterol, LDL, hemoglobin, hematocrit, and residual renal function, and significantly higher serum ferritin, hsCRP, IL-6, TNFalpha, and erythropoietin dose. The difference in serum prohepcidin and hepcidin did not reach statistical significance; however, there was a tendency toward higher values of both prohepcidin and hepcidin in hyporesponsive patients. In conclusion, though hyporesponsiveness to erythropoietin therapy occur in dialyzed patients, it is mainly associated with subclinical inflammation than with hepcidin excess. Further studies are needed to develop a reliable and reproducible assay to elucidate the potential contribution of hepcidin to hyporesponsiveness during erythropoietin therapy.

Unlabelled: Neutrophil gelatinase-associated lipocalin (NGAL) has recently been proved useful in the quantitation of chronic kidney disease. A cross-sectional study was performed to assess NGAL in serum, urine and ultrafiltrate in relation to the type of renal replacement therapy and NGAL correlations with renal function and markers of inflammation., Methods: NGAL, hsCRP, TNFalpha, and IL-6 were measured using commercially available kits in 200 patients on hemodialysis (HD), 17 on hemodiafiltration (HDF)., Results: Patients on HDF had lower serum NGAL than those on HD. In hemodialyzed patients with residual renal function, serum NGAL was significantly lower than in anuric patients. NGAL was significantly higher in patients dialyzed on modified cellulose dialyzers versus polysulphone dialyzers. NGAL correlated with age, residual renal function, hsCRP, IL-6, TNF-alpha, time on HD, ferritin, TSAT, creatinine, urea, urea reduction ratio, and Kt/V in hemodialyzed patients. In multiple regression analysis, residual renal function and hsCRP were predictors of NGAL in hemodialyzed patients. NGAL correlated with hsCRP and creatinine in HDF patients., Conclusions: Residual renal function seems to play a pivotal role in NGAL levels in dialyzed patients. Low-grade inflammation, more pronounced in anuric patients may also contribute to elevated NGAL. Removal of NGAL with ultrafiltrate may also partially explain its lower concentration after dialysis., (Copyright 2009 S. Karger AG, Basel.)

Unlabelled: Hepcidin is a small defensin-like peptide, the production of which by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Kidneys are involved in not only the synthesis of hepcidin, but they also may be involved in its elimination. A cross-sectional study was performed to assess prohepcidin and hepcidin in serum, urine, and ultrafiltrate/peritoneal effluent in relation to type of renal replacement therapy and prohepcidin and hepcidin correlations with renal function, iron status, and markers of inflammation., Methods: Prohepcidin and hepcidin high-sensitivity CRP, TNF alpha, and IL-6 were measured using commercially available kits in 102 patients on hemodialyses, 17 on hemodiafiltration, 44 on peritoneal dialyses, and 22 healthy volunteers., Results: In hemodialyzed and peritoneally dialyzed patients with residual renal function, serum prohepcidin (264.21 +/- 95.84 vs. 341.84 +/- 90.45 ng/mL, p < 0.01; 142.76 +/- 57.87 vs. 238.42 +/- 84.32 ng/mL, p < 0.01, respectively) and hepcidin (178.89 +/- 89.87 vs. 295.76 +/- 129.65 ng/mL, p < 0.01; 108.43 +/- 75.49 vs. 186.53 +/- 119.62 ng/mL, p < 0.01, respectively) were significantly lower than in anuric patients. In peritoneal effluent, prohepcidin level was significantly higher than in ultrafiltrate of HD/HDF patients. In multiple regression analysis, residual renal function, ferritin, and hsCRP were predictors of hepcidin in hemodialyzed patients, while residual renal function and ferritin were predictors of hepcidin in peritoneally dialyzed patients., Conclusions: Residual renal function seems to play a pivotal role in hepcidin levels in dialyzed patients. In addition, the presence of low-grade inflammation, more pronounced in anuric patients, and functional iron deficiency may also contribute to the elevated hepcidin. The removal of prohepcidin with ultrafiltrate/peritoneal effluent may partially explain its lower concentration in peritoneal dialysis and hemodiafiltration.

Background: 39 end-stage renal disease (ESRD) patients undergoing elective coronary angiography (CA) were studied., Method: Myocardial contrast echocardiography (MCE) for the perfusion assessment was done prior to CA. The left ventricle was divided into three regions supplied by left anterior descending (LAD) circumflex (Cx) and right coronary artery (RCA). Comparison between MCE and CA was performed on two levels: presence of any perfusion defect by any significant coronary artery stenosis (CAS) in a particular patient, any perfusion defect-by-vessel analysis., Results: Significant coronary artery disease was revealed on CA in 18 (46%) patients. 28 (72%) of the patients had perfusion defects on MCE. The sensitivity, specificity, positive and negative predictive values (PPV, NPV) of MCE for the presence of any significant CAS in a given patient were 94, 76, 77 and 94% respectively. The best agreement between the presence of the perfusion defect on MCE and CAS was found for RCA: sensitivity 89%, specificity 87%, PPV 67%, NPV 96%, the worst for LAD: 71, 71, 53 and 91% respectively., Conclusion: Our preliminary results indicate that MCE is of a good accuracy for ruling out the presence of a significant CAS in patients with ESRD. Diagnostic performance of MCE seems to be different in respect of analyzed region of the left ventricle., (Copyright 2008 S. Karger AG, Basel.)

The current Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines advocate creatinine-based equations for estimating GFR to identify patients with potential kidney disease and classify them into different stages due to the fact that serum creatinine is very insensitive to changes in the glomerular filtration rate. Very few biomarkers exist for monitoring chronic kidney disease. The aim of the study was to assess whether NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD. The study was performed on 92 non-diabetic patients with CKD stages 2-4. Serum and urinary NGAL as well as serum cystatin C were measured using commercially available kits. Serum NGAL was related, in univariate analysis, to serum creatinine, urinary NGAL, hemoglobin, hematocrit, leukocyte count, eGFR, and cystatin C. Urinary NGAL correlated with age, hemoglobin, hematocrit, serum creatinine, and eGFR. In multiple regression analysis, predictors of serum NGAL were creatinine (beta value = 0.97, p = 0.005), cystatin C (beta = 0.34, p = 0.01), and eGFR (beta value = 1.77, p = 0.001). In the healthy volunteers, serum NGAL correlated with age, serum creatinine, eGFR, leukocyte count, and cystatin C. Taking into consideration the fact that the recent DOQI (Dialysis Outcomes Quality Initiative) states that individuals with reduced GRF (glomerular filtration rate) are at greater risk for CVD and cardiac deaths, precise evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. NGAL should be investigated as a potential early and sensitive marker of kidney impairment/injury.

Objective: Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and inflammation are common complications of kidney diseases. Endothelial dysfunction may link these two processes., Design and Patients: A cross-sectional study on thyroid hormones in relation to markers of endothelial damage and inflammation in 96 hemodialyzed (HD) patients and 39 healthy volunteers was performed., Setting: The study took place in the dialysis unit at a university hospital., Intervention: Thyroid hormones, markers of endothelial damage (von Willebrand factor, thrombomodulin, intracellular adhesion molecule, and CD146), markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor alpha), other hemostatic parameters (thrombin-antithrombin complexes, prothrombin fragments 1 + 2 - F1 + 2, plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, tissue factor pathway inhibitor, and platelet glycoprotein V) were measured using commercially available kits., Results: Free T3 and total T3 were lower in HD patients compared with controls. Markers of endothelial dysfunction and inflammation were significantly elevated in HD patients compared with controls. In multiple regression analysis T3 was independently related to time on dialyses, albumin, iron, ferritin, C-reactive protein (CRP), and F1 + 2 in HD patients. Free T3 was also independently related to total protein, total calcium, and triglycerides. In patients with CRP less than 6 mg/L in multiple regression analysis the only correlates of T3 were albumin and ferritin, whereas the only correlates of free T3 were albumin and time on dialyses. Multiple regression analysis showed that in HD patients with CRP greater than equal to 6 mg/L predictors of free T3 were CRP, F1 + 2, and dose of erythropoietin. In healthy volunteers T3 was related to tissue factor pathway inhibitor and platelet glycoprotein V was related to thyroid-stimulating hormone., Conclusions: We described novel relations between thyroid hormones and markers of endothelial dysfunction and inflammation in HD patients. Thyroid dysfunction is related to time on dialyses, endothelial damage, and inflammatory state, frequently encountered in uremia. Therefore, the relations between thyroid axis and endothelium in HD subjects merit additional studies.

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 single best predictor of mortality in patients with chronic kidney disease and in kidney transplant recipients. These populations are considered to be at extraordinarily high risk for CVD and its complications. On the other hand, renal dysfunction should be considered as a CVD risk factor. The management of CVD in patients with chronic kidney disease is a special challenge for clinicians. In this article, major risk factors for CVD are presented, as well as diagnosis of coronary artery disease, acute coronary syndromes, its treatment modalities (pharmacological therapy and coronary revascularisation procedures), and outcomes in patients with chronic renal failure and kidney allograft recipients.

Background: Dyslipidemia and increased mortality due to cardiovascular events are common in peritoneally dialyzed patients [continuous ambulatory peritoneal dialysis (CAPD)]. Statins show beneficial effects on serum lipids and reduce cardiovascular mortality. The CD40-CD40 ligand (CD40L) system has proved critical for the activation of tissue structural cells that include endothelial cells, epithelial cells and fibroblasts. It has been reported that enhanced CD40L-CD40 interaction in familial hypercholesterolemia may be downregulated by statins, but prospective studies on CAPD patients are lacking., Aim: To determine the effects of 6 months treatment with simvastatin on platelet aggregation, markers of endothelial cell injury, and sCD40L in 15 hyperlipidemic CAPD patients., Methods: Simvastatin (Zocor, Merck Sharp & Dohme) was given in a dose of 10 mg at bedtime., Results: CD40L decreased significantly after 6 months of the therapy. Thrombomodulin decreased significantly after 3 months of the therapy, whereas von Willebrand factor, E-selectin and P-selectin did not change significantly during the study., Conclusion: Simvastatin reduced enhanced sCD40L levels together with amelioration of endothelial dysfunction. Treatment with simvastatin might downregulate enhanced CD40L-CD40 interactions in CAPD patients.

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.

Objective: Bleeding diathesis and simultaneous thrombotic complications may be seen in dialyzed patients. Erythropoietin (EPO) may shift the precarious balance of the hemostatic system toward thrombosis. Platelets and tissue factor (TF) play a major role in plug formation. Tissue factor pathway inhibitor (TFPI) appears to play a primary role in regulating TF-induced coagulation. Thrombin activatable fibrinolysis inhibitor (TAFI) is a key protein linking coagulation and fibrinolysis. The aim of the study was to assess whether 6 months of EPO therapy affects platelet function, that is, platelet aggregation and P-selectin level; moieties of the extrinsic coagulation pathway: TF, TFPI, and TFPI/Xa complexes, and factors VII and X; markers of ongoing coagulation: thrombin-antithrombin complexes (TAT) and prothrombin fragments 1+2; a marker of ongoing fibrinolysis: plasmin-antiplasmin complexes (PAP); fibrinolytic activity: euglobulin clot lysis time (ECLT); and markers of endothelial cell injury: von Willebrand factor, thrombomodulin, E-selectin, and TAFI, in continuous ambulatory peritoneal dialysis (CAPD) patients., Patients and Methods: 22 patients on CAPD were given EPO 6,000 U/week. 12 patients with chronic renal failure and 12 healthy volunteers served as control groups. All parameters were studied before, and after 1, 3, and 6 months of EPO therapy., Setting: Department of Nephrology and Internal Medicine, Medical Academy of Bialystok, Poland., Results: Platelet aggregation in whole blood did not change significantly during EPO treatment. A significant rise in arachidonic acid-induced platelet aggregation in platelet-rich plasma was observed after 3 and 6 months, and in collagen-induced platelet aggregation after 6 months of EPO therapy, compared to the baseline values. The TFPI concentration decreased significantly after 6 months of EPO therapy. The activity of factor VII increased transiently after 1 month of EPO therapy, compared to the baseline values. The TAFI concentration and activity in the CAPD group were significantly higher than in the control group. Erythropoietin therapy resulted in a significant decrease in TAFI concentration and activity after 6 months of EPO treatment. The ECLT was shortened significantly as early as after 1 month of EPO therapy. Thrombomodulin, von Willebrand factor concentration and activity, PAP, TAT, TFPI/Xa complexes, prothrombin fragments 1+2, factor X activity, P-selectin, E-selectin, and lipoprotein(a) did not change significantly during EPO treatment., Conclusion: Erythropoietin treatment has a minimal effect on hemostasis in CAPD patients. A tendency toward a decline in TAFI is of unknown clinical relevance so far, and awaits further research.