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There is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment, especially due to vascular damage, blood–brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotropic agents, drugs with anticholinergic properties, GABAergic drugs, opioids, corticosteroids, antibiotics and others have been linked to negative effects on cognition. These drugs are frequently included in the treatment regimen of CKD patients. The first review of this series described how CKD could represent a risk factor for adverse drug reactions affecting the central nervous system. This second review will describe some of the most common medications associated with cognitive impairment (in the general population and in CKD) and describe their effects. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) is a frequent postoperative complication. However, data on the incidence of AKI in patients with colorectal cancer (CRC) undergoing surgery with curative intent are still limited. We examined the relationship between postoperative AKI among CRC surgery patients and preoperative therapy or no prior therapy. Material and methods: A total of 326 consecutive patients from the regional oncology center undergoing CRC surgery in the period January to December 2019 were included in the observational cohort study. We defined AKI as a 50% increase in plasma creatinine or initiation of renal replacement therapy within 7 days after surgery or an absolute increase in creatinine of 0.3 mg/dl within 48 hours. Results: Acute kidney injury occurred in 36 patients (11%), 27 of whom underwent rectum resection, and 9 underwent colon resection. The incidence of AKI was identical in both types of surgery. Among 54 patients undergoing neoadjuvant radiochemotherapy, 6 patients (11%) developed AKI, while there was no case of AKI in 31 patients with neoadjuvant radiotherapy. Among 36 patients with AKI, 33 had hypertension, 27 had diabetes and 18 had at least stage 3 of chronic kidney disease before the surgery. Conclusions: Acute kidney injury after surgery for CRC is a relatively frequent postoperative complication, in particular, in patients with prior impairment in kidney function and comorbidities such as hypertension and diabetes. Appropriate preoperative therapy, including optimal hydration, withdrawal of potentially nephrotoxic drugs, etc., may reduce the incidence of AKI. [ABSTRACT FROM AUTHOR]

• High-resolution computed tomography (HRCT) was performed in potential kidney transplant recipients; however, it was intended to exclude the possibility of COVID-19 infection and to provide additional data, including extrapulmonary pathologies. • Despite the possibility of overdiagnosis by HRCT, HRCT should be considered a standard evaluation technique performed in potential kidney transplant recipients. Kidney transplant is the preferred treatment for most patients with end-stage renal disease. Because dialyzed patients often have significant comorbidities or multimorbidities, they should be carefully evaluated before being waitlisted for transplant. The COVID-19 pandemic presents a major challenge for surgery, including transplant surgery. Owing to a fear of COVID-19 symptoms occurring in lungs, thin-section computed tomography (TSCT) became a standard evaluation technique in potential kidney transplant recipients before surgery. The aim of the study was to evaluate the rationale and usefulness of TSCT in deceased donor kidney transplant during the COVID‐19 pandemic. All adult patients who underwent deceased donor kidney transplant between May 1, 2020, and December 15, 2021, were included in the study. Potential kidney transplant recipients who were admitted to the Department of General, Vascular , and Transplant Surgery at the Medical University of Warsaw in Warsaw, Poland, were tested for COVID-19 (CovGenX rapid test); blood chemistries were performed; dialysis was performed (if needed); and, on a negative reverse transcriptase polymerase chain reaction test , HRCT was performed. From May 2020 until the end of December 2021, 54 patients were transplanted; however, 7 patients were disqualified after TSCT and consulted with a pulmonary specialist. Disqualification from kidney transplant accounted for 13% of the potential kidney allograft recipients. Despite the possibility of overdiagnosis by TSCT, TSCT should be considered a standard evaluation technique in potential kidney transplant recipients. Potential kidney transplant recipients must be periodically reassessed given the prolonged wait time for a donor kidney and the significant number of comorbid conditions in this patient population. However, more data with longer follow‐ups are needed to prove or disprove the rationale to use TSCT in transplant surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a very common condition with high morbidity and mortality, which can be seen in 5–7% of all hospitalized patients and in up to 57% of all intensive care unit admissions. Despite recent advances in clinical care, the prevalence of AKI has been shown to increase with virtually no change in mortality. AKI is a complex syndrome occurring in a variety of clinical settings. Early detection is crucial to prevent irreversible loss of renal function. The pathogenesis of AKI is highly multifactorial and complex, including vasoconstriction, reactive oxygen species formation, cell death, abnormal immune modulators and growth factors. Emerging evidence from both human and animal studies suggests that dysregulation of iron metabolism may play a potentially important role in AKI. Therefore, targeting the iron homeostasis may provide a new therapeutic intervention for AKI. New therapeutic strategies including iron chelation therapy, targeting iron metabolism related proteins and direct inhibitors of ferroptosis are imperative to improve the outcomes of patients. Taking into consideration the complexity of AKI, one intervention may not be enough for therapeutic success. Future preclinical studies in animal disease models followed by well-designed clinical trials should be conducted to extend findings from animal AKI models to humans. [ABSTRACT FROM AUTHOR]

Background: Tumor lysis syndrome (TLS) is an oncologic emergency due to a rapid break down of malignant cells usually induced by cytotoxic therapy, with hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and serious clinical consequences such as acute renal injury, cardiac arrhythmia, hypotension, and death. Rapidly expanding knowledge of cancer immune evasion mechanisms and host-tumor interactions has significantly changed our therapeutic strategies in hemato-oncology what resulted in the expanding spectrum of neoplasms with a risk of TLS. Summary: Since clinical TLS is a life-threatening condition, identifying patients with risk factors for TLS development and implementation of adequate preventive measures remains the most critical component of its medical management. In general, these consist of vigilant laboratory and clinical monitoring, vigorous IV hydration, urate-lowering therapy, avoidance of exogenous potassium, use of phosphate binders, and – in high-risk cases – considering cytoreduction before the start of the aggressive agent or a gradual escalation of its dose. Key Messages: In patients with a high risk of TLS, cytotoxic chemotherapy should be given in the facility with ready access to dialysis and a treatment plan discussed with the nephrology team. In the case of hyperkalemia, severe hyperphosphatemia or acidosis, and fluid overload unresponsive to diuretic therapy, the early renal replacement therapy (RRT) should be considered. One must remember that in TLS, the threshold for RRT initiation may be lower than in other clinical situations since the process of cell breakdown is ongoing, and rapid increases in serum electrolytes cannot be predicted. [ABSTRACT FROM AUTHOR]

Acute and chronic kidney disease encompasses a complex set of diseases that can both lead to, and result from, cancer. In particular, kidney disease can arise from the use of chemotherapeutic agents. Many of the current and newly developed cancer chemotherapeutic agents are nephrotoxic and can promote kidney dysfunction, which frequently manifests during the terminal stages of cancer. Given the link between kidney disease and cancer development and treatment, the aim of this Review is to highlight the importance of multidisciplinary collaboration between oncologists and nephrologists to predict and prevent chemotherapeutic-induced nephrotoxicity. As new therapies are introduced to treat cancer, new renal toxicities require proper diagnosis and management. We anticipate that multidisciplinary collaborations will lead to the development and implementation of guidelines for clinicians to improve the therapeutic management of patients with both cancer and renal impairment. [ABSTRACT FROM AUTHOR]

Introduction: The clinical courses of takotsubo syndrome (TS) and of acute coronary syndromes (ACS) seem to be very similar. However, there is limited knowledge about risk factors of poor outcomes. Low body mass index worsens the prognosis of patients with cardiovascular diseases, especially those undergoing surgical treatment. The aim of the study was to evaluate the influence of the body mass index (BMI) on the prognosis in patients diagnosed with TS.Material and Methods: Eighty patients aged 15-89 (mean: 67.9 years), 74 women and 6 men with TS diagnosis according to Mayo Clinic diagnostic criteria were divided into 3 groups: low body mass (BMI < 18.5 kg/m2), normal body mass (18.5 ≥ BMI < 25 kg/m2) and excessive body mass (BMI ≥ 25 kg/m2).Results: Patients with low BMI were older, but with less prevalent risk factors such as hypertension, hypercholesterolemia and positive family history of coronary artery disease and more frequent risk factors such as cigarette smoking, chronic obstructive pulmonary disease (COPD), depressive and anxiety disorders as well as malignancy. They also had higher haemoglobin, lower troponin, creatine kinase, C-reactive protein and lipid fractions. The highest annual, 3-year and 5-year mortality was observed in the group with BMI < 18.5 kg/m2. None of the patients with low BMI survived the 5-year follow-up period (100% vs. 25% vs. 15.2%; p < 0.0001). In group III, mortality among overweight patients (25 ≥ BMI < 30 kg/m2) was 8.3%, and in obese people (BMI ≥ 30 kg/m2) 1 out 5 patients died during follow-up.Conclusions: The majority of typical cardiovascular risk factors are less frequently observed in patients with TS and low body mass. Early prognosis for TS patients and low BMI is relatively favourable, whereas the 5-year follow-up is associated with extremely high mortality. Overweight patients have the best prognosis in the long-term follow-up. [ABSTRACT FROM AUTHOR]

Contrast-induced acute kidney injury (CI-AKI) is a common and potentially serious complication of percutaneous coronary interventions (PCI). In this study, we tested the hypothesis whether serum and urinary hepcidin could represent early biomarkers of CI-AKI in patients with normal serum creatinine undergoing PCI. In addition, we assessed serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, eGFR and serum creatinine in these patients. Serum and urinary hepcidin and NGAL, serum cystatin C, were evaluated before, and after 2, 4, 8, 24 and 48 h after PCI using commercially available kits. Serum creatinine was assessed before, 24 and 48 h after PCI. We found a significant rise in serum hepcidin as early as after 4 and 8 h when compared to the baseline values. Serum NGAL increased after 2, 4 and 8 h, and in urinary NGAL after 4, 8 and 24 h after PCI. We found a significant fall in urinary hepcidin after 8 and 24 h after PCI. Serum cystatin C increased significantly 8 h after PCI, reaching peak 24 h after PCI and then decreased after 48 h. The prevalence of CI-AKI was 8%. Urine hepcidin was significantly lower 8 and 24 h after PCI in patients with CI-AKI, while serum and urine NGAL were significantly higher in patients with CI-AKI. Our findings suggest that serum hepcidin might be an early predictive biomarker of ruling out CI-AKI after PCI, thereby contributing to early patient risk stratification. However, our data needs to be validated in large cohorts with various stages of CKD. [ABSTRACT FROM AUTHOR]

Sirtuins represent a group of nicotinamide adenine dinucleotide dependent histone deacetylases, which regulates various biological pathways by promoting chromatin silencing and transcriptional repression. Therefore, they are linked to cellular energy metabolism, mitochondrial biogenesis, stress response, apoptosis, inflammation and fibrosis. Since sirtuin 1 became a promising candidate for targeted therapies of numerous conditions, researchers have been investigating its activator. As for now, natural agents and antidiabetic drug – metformin, have been found to activate sirtuin 1. Sirtuin 1 is able to improve kidney outcomes by direct impact on kidney cells, regulation of non-specific processes generally involved in pathogenesis of age–dependent and metabolic disorders and improvement of the comorbid diseases. This review discusses the state of the art knowledge on the role of sirtuin 1 on kidney pathology. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy of renal significance (MGRS) has introduced a new perspective to several well-known disease entities impacting nephrology, haematology and pathology. Given the constantly changing disease spectrum of these entities, it is clinically imperative to establish diagnostic and treatment pathways supported by evidence-based medicine. MGRS is a disease of the kidney, secondary to plasma cell clonal proliferation or immune dysfunction, requiring therapeutic intervention to eradicate the offending clone. To fully understand the disease(s), it is prerequisite to determine the significance of the findings. The diagnostic work up should be extensive due to the wide heterogeneity of clinical presentation, ultimately necessitating kidney biopsy. Particular patient profiles such as AL amyloidosis, which may be diagnosed through biopsies of other tissues/organs, may be an exception. Treatment decisions should be formulated by multi-disciplinary consensus: nephrologists, haematologists and pathologists. The ultimate goal in managing MGRS is eradication of the offending plasma cell clone which requires targeted chemotherapy and, in eligible cases, haematopoietic stem cell transplantation. We present a review of diagnostic procedures, treatment options and advances in the last few years in the management of MGRS in an effort to acquaint specialists with this new face of several older diseases. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia of high clinical importance, occurring in 2% of the general population and in 19–24% in patients with chronic kidney disease. It is a well-known risk factor for cardiovascular morbidity and mortality. Kidney transplant recipients with a history of AF were associated with significantly higher rate of ischaemic strokes, graft failure and post-transplant mortality. AF occurs in over 7% of kidney transplant recipients in the first 3 years after transplantation and is associated with reduced graft and patient survival. The incidence of stroke in patients after kidney transplantation (KTx) is higher than the general population, but markedly lower than those on dialysis. Oral anticoagulation (OAC) therapy is recommended in AF patients at high risk of stroke. There are no randomized studies assessing OAC in patients after KTx and there are no specific recommendations and guidelines on therapeutic strategies in these patients. KTx recipients are a vulnerable population, exposed to variations in renal function, being at higher risk of bleeding and thrombotic complications, with possible interactions with immunosuppression. Surely, there is a place for novel oral anticoagulants (NOACs) in this group of patients as long as the summary of product characteristics is followed, as they are a valuable anticoagulation therapy. On one hand, they are at least as effective as warfarin; on the other hand NOACs are safer, especially when it comes to intracranial haemorrhages. However, NOACs seem to be underused in this population as they are excreted via kidney, may interact with immunosuppressive therapy and physicians need more experience and confidence in their administration. Percutaneous left atrial appendage occlusion procedure may also be considered as an opportunity for this group of patients, in particular in the presence of contraindications to anticoagulation. [ABSTRACT FROM AUTHOR]

Iron deficiency anaemia is a global health problem that manifests as fatigue and poor physical endurance. Anaemia can be caused by dietary iron deficiency, blood loss or a combination of poor iron absorption and ineffective iron mobilization in patients with chronic disease. Nephrologists caring for patients with impaired renal function understand that iron treatment is necessary to provide adequate iron for erythropoiesis during the treatment of overt anaemia. However, a less wellunderstood health problemis iron deficiency, which creates symptoms that overlap with those of anaemia and often occurs in concert with chronic disease. Recently, several randomized controlled clinical trials have been conducted to investigate the effects of treatment with intravenous iron in heart failure patients with iron deficiency who may or may not also have anaemia. Given that heart and kidney disease are often comorbid, these clinical trials may have implications for the way nephrologists view their patients with iron deficiency. In this article, we review several clinical studies of intravenous iron therapy for patients with iron deficiency and heart failure and discuss possible implications for the treatment of patients with kidney disease. [ABSTRACT FROM AUTHOR]

We tested the hypothesis whether midkine could represent an early biomarker of contrast-induced acute kidney injury (CIAKI) in 89 patients with normal serum creatinine undergoing PCI. Midkine, serum and urinary NGAL, and cystatin C were evaluated before and 2, 4, 8, 24, and 48 hours after PCI using commercially available kits. Serum creatinine was assessed before and 24 and 48 hours after PCI. We found a significant rise in serum midkine as early as after 2 hours (P<0.001) when compared to the baseline values. It was also significantly higher 4 hours after PCI and then returned to the baseline values after 24 hours and started to decrease after 48 hours. When contrast nephropathy was defined as an increase in serum creatinine by >25% of the baseline level 48 hours after PCI, the prevalence of CIN was 10%. Patients with CIN received significantly more contrast agent (P<0.05), but durations of PCI were similar. Midkine was significantly higher 2, 4, and 8 hours after PCI in patients with CIN. Since the “window of opportunity” is narrow in CIAKI and time is limited to introduce proper treatment after initiating insult, particularly when patients are discharged within 24 hours after the procedure, midkine needs to be investigated as a potential early marker for renal ischemia and/or nephrotoxicity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Hypertension and cardiovascular complications are very common in chronic kidney disease (CKD). Overactivation of sympathetic nervous system is also widely recognized in CKD. Renalase may play an important role in the control of blood pressure (BP) by its regulatory function of catecholamine metabolism. Renalase could be synthesized not only by the kidney but also by cardiomyocytes, liver, and adipose tissue. It probably exerts a hypotensive action, at least in animal models. Whether it metabolizes catecholamines remains to be proved. Another issue that remains to be resolved is the relationship between renalase and renal natriuresis and phosphaturia. In this review, the updated experimental and clinical data on renalase are presented and possible interactions with the endothelium are discussed. Renalase is “a new postulated therapeutic target.” Proof of concept studies are needed to define the pathophysiological link between the kidney, sympathetic tone, BP, and cardiovascular complications. [ABSTRACT FROM PUBLISHER]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-trasnplant anemia, as well as for post transplant erythrocytosis, another hematological disorder, that has decreased in recent years. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) affects the crosstalk between organs in the body and vast majority of studies were devoted to the interactions between the kidneys and the cardiovascular system. As of today, there is more evidence of the kidney and the central nervous system connections. Summary: Indeed, CKD and in particular dialysis therapy is linked to the increased prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment, and depression. Both traditional cardiovascular risk factors (such as diabetes, hypertension, and lipid disorders), nontraditional risk factors (such as uremic toxins, anemia, and secondary hyperparathyroidism) may predispose CKD patients to neurological disorders. Likewise, cognitive problems occur more commonly in kidney transplant recipients, regardless of age, than in the general population, but the prevalence is still understudied. Cognitive impairment is associated with a higher risk of hospitalization, mortality, decreased quality of life, or health care costs in kidney transplant recipients. Here, we review (i) the potential clinical impact of kidney transplantation on cerebrovascular and neurological complications, (ii) evaluation of patients with cognitive impairment for kidney transplantation (iii) the potential impact of cognitive impairment on waitlisted and transplanted patients on patient care, and (iv) unmet medical needs. Key Messages: Cognitive impairment in kidney transplant recipients is an underestimated, underrecognized but clinically relevant problem. The screening for cognitive declines after kidney transplantation is not yet a routine practice. Several prospective and cross-sectional studies reported improvement across some of the assessed cognitive domains after transplantation. [ABSTRACT FROM AUTHOR]

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 p,g/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 ((3-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. [ABSTRACT FROM AUTHOR]

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.' [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is diagnosed in 5% of all hospitalized patients and in up to 50% of all ICU patients. In the last years a dramatic rise in the prevalence of AKI has been observed with virtually no change in mortality, reaching up to 50-80% in all dialyzed ICU patients. AKI may progress to end-stage renal disease, and even subclinical episodes of AKI, which are common, may also progress to end-stage renal disease. The early detection of AKI may enable timely intervention and prevention of progression; however, in animal models and in human studies the 'window of therapeutic intervention' is narrow. Different urinary and serum proteins have been intensively investigated as possible biomarkers for the early diagnosis of AKI. There are promising candidate biomarkers with the ability to detect an early and graded increase in tubular epithelial cell injury and distinguish pre-renal disease from acute tubular necrosis. In this review, new emerging biomarkers of AKI are presented and described in some clinical settings, such as cardiac surgery, contrast-induced nephropathy, delayed graft function and ICU/emergency departments, where biomarkers are urgently needed to diagnose, make prognoses and differentiate. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Endothelium is the largest organ in the body strategically located between the wall of blood vessels and the blood stream. The human body contains approximately 1013 endothelial cells weighing approximately 1kg, and covering a surface area of 4000 to 7000m2 equivalent to the soccer playground. Hypertension and shear stress, inflammation, diabetes-associated factors such as advanced glycated end products, and uremic toxins are some of the prevalent risk factors of endothelial dysfunction in chronic kidney disease. In renal failure endothelial dysfunction and atherosclerosis are almost universal, as well as cardiovascular complications. Endothelial cell damage or injury is invariably associated with such clinical conditions as thrombosis, hypertension, renal failure and atherosclerosis and may be also responsible for accelerated atherosclerosis in patients with chronic renal failure. Traditional risk factor cannot explain the high prevalence and incidence of cardiovascular disease in chronic kidney disease, therefore other non-traditional risk factors such as endothelial dysfunction, oxidative stress or insulin resistance have increasingly been studied. In this review paper mechanism of endothelial dysfunction, including the role of nitric oxide pathway, adipocytokines and hemodialysis-induced endothelial dysfunction is discussed. [Copyright &y& Elsevier]

Background: Neutrophil gelatinase-associated lipocalin (NGAL) binds small, iron-carrying molecules – siderophores. On the other hand, hepcidin is a small defensin-like peptide produced by hepatocytes, modulated in response to anaemia, hypoxia, or inflammation. We tested the hypothesis that NGAL may be related to hepcidin, not only to iron metabolism, in 182 prevalent haemodialysed patients. Methods: Iron status (iron, total iron-binding capacity, ferritin, total saturation of transferrin, TSAT), complete blood count, creatinine, albumin, serum lipids were assessed using standard laboratory methods. Soluble receptor of transferrin, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, prohepcidin, hepcidin and NGAL were measured in serum using commercially available kits. Results: Serum NGAL, prohepcidin, hepcidin levels were significantly higher in haemodialysed patients over healthy volunteers (579.11 ± 213.95 vs. 78.43 ± 32.21 ng/ml, p < 0.001, 320.54 ± 182.65 vs. 98.65 ± 34.32 ng/ml, p < 0.01, 155.30 ± 94.05 vs. 23.65 ± 12.76 ng/ml, p < 0.001, respectively). Serum NGAL correlated strongly with residual renal function (r = –0.54, p < 0.001), Kt/V (r = 0.41, p < 0.001), hepcidin (r = –0.28, p < 0.01), serum creatinine (r = 0.63, p < 0.001), iron (r = 0.25, p < 0.01), TSAT (r = 0.30, p < 0.001), ferritin (r = 0.33, p < 0.001), hsCRP (r = 0.32, p < 0.001). In multiple regression analysis, residual renal function, hepcidin, creatinine and hsCRP were predictors of serum NGAL in haemodialysed patients. Conclusions: NGAL is highly induced in dialysed patients. NGAL could reflect both kidney function and iron metabolism. Taking into account the antimicrobial properties of NGAL, further studies are needed to address the role of NGAL in iron metabolism and inflammation in renal failure. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Iron is the fourth most common element in the Earth’s crust and is crucial for life. Over the last few years, our understanding of iron metabolism has dramatically increased due to the discovery of hepcidin, which is produced by hepatocytes and modulated in response to anemia, hypoxia and inflammation. It has been found that anemia upregulates lipocalin 2 (NGAL; neutrophil gelatinase-associated lipocalin) in the liver and serum. The aim of this review is to summarize the current knowledge dealing with a possible role of hepcidin and NGAL in iron metabolism and its regulation, particularly in kidney disease. Elevated NGAL a few days after insult is a possible preventive or protective mechanism limiting renal injury. NGAL is an innate antibacterial factor as well as hepcidin. NGAL binds siderophores, thereby preventing iron uptake by bacteria. Hepcidin, an antibacterial defensin, prevents iron absorption from the gut and iron release from macrophages, leading to hypoferremia and anemia. Both proteins sequester iron, but by different mechanisms. However, these proteins involved in iron metabolism do not seem to be independently related. Taking into account the antimicrobial moieties of NGAL, further studies are needed to address the role of NGAL in iron metabolism and inflammation in renal failure. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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-α (TNF-α) and interleukin (IL)-6) were assessed. Results: Triglycerides, hsCRP, creatinine, IL-6, TNF-α, 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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the study which focuses on the impact of the reuse of dialyzer on the adequacy of dialysis, anemia control, and erythropoieting-stimulating agents (ESA).

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, TNFα, 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-α, 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 © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aims. Different serum and urinary biomarkers have been recently proposed to serve as markers of acute kidney injury. We tested the hypothesis whether NGAL and other biomarkers could represent an early biomarker of contrast nephropathy (CIN) in diabetic patients with normal serum creatinine undergoing cardiac catheterization in comparison with non-diabetic patients. Methods. Serum, urinary NGAL, cystatin C, urinary kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and liver-type fatty acid binding protein (L-FABP) were evaluated before and 2, 4, 8, 24, and 48 hours after cardiac catheterization using commercially available kits. Results. In both groups we found a significant rise in serum NGAL after 2, 4, and 8 hours, and in urinary NGAL and IL-18 after 4, 8, and 24 hours after cardiac catheterization. Serum cystatin C increased significantly 8 hours, reaching peak 24 hours after cardiac catheterization in both groups, and then decreased after 48 hours. L-FABP and KIM-1 increase significantly after 24 and 48 hours after cardiac catheterization. Conclusions. CIN was similarly prevalent in both diabetic and non-diabetic patients undergoing cardiac catheterization. NGAL seems to be a potential early marker for nephrotoxicity and predictor of contrast nephropathy. It is particularly important in the upcoming setting of short-time hospitalizations for cardiac catheterization. [ABSTRACT FROM AUTHOR]

Hepcidin is the predominant negative regulator of iron absorption in the small intestine, iron transport across the placenta, and iron release from the macrophages. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietin-stimulating agents. The aim of this study was to assess hepcidin levels in 12 hemodialyzed (HD) patients (6 females, 6 males, mean age 64 years, mean time on HD 36 months) before and after intravenous iron therapy. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Marburg, Germany (ELISA method), and Bachem, St. Helens, UK (RIA method). Soluble receptor of transferrin was studied using a kit from R&D, Abington, UK. We found a significant rise in hemoglobin concentration, hematocrit, ferritin, serum iron, transferrin saturation and a fall in soluble receptor of transferrin. Serum hepcidin and prohepcidin as well as urinary prohepcidin increased significantly after the therapy. In conclusion, hepcidin levels are influenced by iron supplementation in HD patients. Further examinations of hepcidin as a marker of iron deficiency using new validated measurement techniques are required. It remains to be seen if assay of hepcidin will be of help in identifying patients unresponsive to oral iron or requiring intravenous iron supplementation. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). TNFα 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, TNFα, 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. [ABSTRACT FROM AUTHOR]

Hemojuvelin (HJV) is a membrane protein that is responsible for the iron overload condition known as juvenile hemochromatosis. HJV, highly expressed in the liver, skeletal muscle and heart, seems to play a role in iron absorption and release from cells and has anti-inflammatory properties. HJV is a bone morphogenetic protein (BMP) co-receptor and signals via the SMAD (human homolog of Drosophila mad – mother against decapentaplegic) pathway to regulate hepcidin expression. HJV acts as a BMP co-receptor. Moreover, HJV plays an essential role in the regulation of hepcidin expression, specifically in the iron-sensing pathway, although through unknown mechanisms. Dietary iron sensing and inflammatory pathways converge in the regulation of the key regulator hepcidin, but how these two pathways intersect remains unclear. Inflammation, through downregulation of hepatic HJV, might induce temporary elimination of iron sensing. Despite enormous scientific achievements in explaining the pathogenetic mechanisms of iron metabolism, many questions still remain unanswered: What is the functional role of HJV in iron metabolism? How it is related to hepcidin expression in different settings? How do iron-sensing and inflammatory pathways cooperate in hepcidin gene expression? Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Heart failure and chronic kidney disease share a number of risk factors and pathophysiological pathways. Renal insufficiency is common in patients with chronic heart failure (CHF). The aim of the study was to assess whether neutrophil gelatinase-associated lipocalin (NGAL) could represent a novel, sensitive marker of kidney function in adult patients with chronic heart failure and normal serum creatinine. The study was performed on 150 patients with chronic heart failure due to coronary artery disease. 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, cystatin C. Urinary NGAL correlated with age, hemoglobin, hematocrit, serum creatinine, eGFR. In multiple regression analysis predictors of serum NGAL were NYHA class, cystatin C, and eGFR. Taking into consideration the fact that the recent DOQI states that individuals with a reduced GFR is at greater risk for cardiovascular disease 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. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Maintaining the correct iron balance is crucial for health. Our understanding of the molecular control of iron metabolism has increased dramatically over the past 5 years due to the discovery of hepcidin. This is a circulating antimicrobial peptide mainly synthesized in the liver, which has been recently proposed as a factor regulating the uptake of dietary iron and its mobilization from macrophages and hepatic stores. Inflammation causes an increase of production of hepcidin, which is a potent mediator of anemia of chronic diseases. Anemia in chronic kidney disease is mainly due to erythropoietin deficiency but these patients often have a chronic inflammatory state. The aim of this review is to summarize the current knowledge dealing with a possible role of hepcidin in iron metabolism and its regulation, particularly in kidney disease. In addition, current methods of determination of hepcidin are reviewed. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]