Search

Patients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO) and its receptor have neuroprotective effects in cell and animal models of nervous system disorders. Recombinant human EPO (rHuEPO), commonly used to treat anemia in CKD patients, could be a neuroprotective agent. In this systematic review, we aimed to assess the published studies investigating the cognitive benefits of rHuEPO treatment in individuals with reduced kidney function. We comprehensively searched Pubmed, Cochrane Library, Scopus, and Web of Science databases from 1990 to 2023. After selection, 24 studies were analyzed, considering study design, sample size, participant characteristics, intervention, and main findings. The collective results of these studies in CKD patients indicated that rHuEPO enhances brain function, improves performance on neuropsychological tests, and positively affects electroencephalography measurements. These findings suggest that rHuEPO could be a promising neuroprotective agent for managing CKD-related cognitive impairment., Competing Interests: Declaration of Competing Interest All authors have no potential conflicts of interest to be disclosed or relevant financial interest in this manuscript. Declaration of interest None No competing interest, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cognitive impairment is common in patients with chronic kidney disease (CKD), and early intervention may prevent the progression of this condition., Methods: Here, we review interventions for the complications of CKD (anemia, secondary hyperparathyroidism, metabolic acidosis, harmful effects of dialysis, the accumulation of uremic toxins) and for prevention of vascular events, interventions that may potentially be protective against cognitive impairment. Furthermore, we discuss nonpharmacological and pharmacological methods to prevent cognitive impairment and/or minimize the latter's impact on CKD patients' daily lives., Results: A particular attention on kidney function assessment is suggested during work-up for cognitive impairment. Different approaches are promising to reduce cognitive burden in patients with CKD but the availabe dedicated data are scarce., Conclusions: There is a need for studies assessing the effect of interventions on the cognitive function of patients with CKD., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Many chemotherapeutic drugs used to treat malignancies undergo renal clearance. Thus, accurate knowledge of kidney function is critical to ensure proper dosing, maximize efficacy, and minimize toxicity of drugs that often have a narrow therapeutic index. Making this issue more salient is the fact that impaired kidney function, as assessed by glomerular filtration rate (GFR), is encountered commonly in patients with cancer. Recent data and expert guidelines recommend the use of the Chronic Kidney Disease-Epidemiology Collaboration equation to guide the assessment of kidney function, except when directly measured GFR is clinically necessary. Controversies regarding the measurement of kidney function include the use of race in this equation, indexing to body surface area, and dosing of medications based on stages of chronic kidney disease versus more discrete values of estimated GFR. The development of accurate, real-time GFR measures may hold great promise in allowing for more accurate dosing of these important drugs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hematopoietic stem cell transplant (HSCT) is used in advanced hematologic diseases to restart the immune system. Kidney damage remains significant complication of hematopoietic cell transplant (HCT) affecting the mortality of transplant recipients. The aim of the study was to assess the advancement of chronic kidney disease (CKD) in patients after HSCT. We studied 150 patients who underwent allo-HSCT treatment in our center in years 1995 to 2020 because of acute myeloid leukemia in 47% of patients, acute lymphoblastic leukemia in 19%, and lymphoma in 32%. The mean age of patients with acute leukemia is 48 years (including acute myeloid leukemia it is 47 years, and including acute lymphoblastic leukemia it is 32 years). The mean age of lymphoma patients is 34 years. We studied the prevalence and stages of CKD. CKD stage 3a and 3b was found in 24.6%. None of the patients studied had CKD stage 4 or 5. In patients after HSCT because of both acute myeloid leukemia and acute lymphoblastic leukemia, CKD stage 3a was found in 19% and stage 3b in 7.3%. Estimated glomerular filtration rate (eGFR) >90 mL/min/1.73 m 2 , was found in 36.8% of this population, whereas eGFR between 90 and 60 mL/min/1.73 m 2 was observed in 36.8%. In patients with lymphoma who underwent HSCT, CKD stage 3a was found in 18%, while CKD stage 3b was diagnosed in 27% of the patients. An eGFR >90 mL/min/1.73 m 2 , was found in 27% of this population, whereas eGFR between 90 and 60 mL/min/1.73 m 2 was observed in 27% of patients. The categorization of patients according to the underlying disease is important because other drugs are used in therapy of conditioning before HCT. CKD in patients after allogeneic HSCT is common, although advanced stages were not observed, probably because the age of the population studied was not advanced. CKD in these vulnerable patients may be because of prior chemotherapy, conditioning regimen, post-HSCT calcineurin therapy, and other possible nephrotoxic drugs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

The aim of the review is to present the most common renal complications after HSCT such as acute kidney injury, chronic kidney disease glomerulopathies. HSCT is a critical therapy for many cancer patients with cancer, as well as patients with some other nonmalignant hematologic disorders and certain congenital immune deficiencies. Kidney complications after HSCT in a form of acute kidney injury is associated with significant morbidity and worse patient outcome. In addition, risk of chronic kidney disease is also increased following HSCT. It is very important to be aware, prevent, early recognize and treat renal damage to improve kidney and patient survival.

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care., (© The Author(s) 2021. Published byOxford University Press on behalf of ERA.)

Post-contrast acute kidney injury (PC-AKI) is one of the side effects of iodinated contrast media, including those used in computed tomography. Its incidence seems exaggerated, and thus we decided to try estimate that number and investigate its significance in our clinical practice. We analyzed all computed tomographies performed in our clinic in 2019, including data about the patient and the procedure. In each case, we recorded the parameters of kidney function (serum creatinine concentration and eGFR) in four time intervals: before the test, immediately after the test, 14-28 days after the test, and over 28 days after the test. Patients who did not have a follow-up after computed tomography were excluded. After reviewing 706 CT scans performed in 2019, we included 284 patients undergoing contrast-enhanced CT and 67 non-enhanced CT in the final analysis. On this basis, we created two comparable groups in terms of age, gender, the severity of chronic kidney disease, and the number of comorbidities. We found that AKI was more common in the non-enhanced CT population (25.4% vs. 17.9%). In terms of our experience, it seems that PC-AKI is not a great risk for patients, even those with chronic kidney disease. Consequently, the fear of using contrast agents is not justified.

Patients with chronic kidney disease (CKD) are at a high risk for cardiovascular disease (CVD), and approximately half of all deaths among patients with CKD are a direct result of CVD. The premature cardiovascular disease extends from mild to moderate CKD stages, and the severity of CVD and the risk of death increase with a decline in kidney function. Successful kidney transplantation significantly decreases the risk of death relative to long-term dialysis treatment; nevertheless, the prevalence of CVD remains high and is responsible for approximately 20-35% of mortality in renal transplant recipients. The prevalence of traditional and nontraditional risk factors for CVD is higher in patients with CKD and transplant recipients compared with the general population; however, it can only partly explain the highly increased cardiovascular burden in CKD patients. Nontraditional risk factors, unique to CKD patients, include proteinuria, disturbed calcium, and phosphate metabolism, anemia, fluid overload, and accumulation of uremic toxins. This accumulation of uremic toxins is associated with systemic alterations including inflammation and oxidative stress which are considered crucial in CKD progression and CKD-related CVD. Kidney transplantation can mitigate the impact of some of these nontraditional factors, but they typically persist to some degree following transplantation. Taking into consideration the scarcity of data on uremic waste products, oxidative stress, and their relation to atherosclerosis in renal transplantation, in the review, we discussed the impact of uremic toxins on vascular dysfunction in CKD patients and kidney transplant recipients. Special attention was paid to the role of native and transplanted kidney function., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Ewa Wojtaszek et al.)

CKD is one of the fastest growing causes of death in the world and in 2040, it is estimated that it will be in the top five causes of death. In order to slow down this process, it is necessary to improve prevention, inhibit development and treat complications including anemia. Anemia is one of the common complication of chronic kidney disease (CKD), which is a significant clinical problem. It is most often the result of decreased renal production of erythropoietin and / or iron deficiency. Iron deficiency anemia is one of the most common problems in CKD that increases mortality. In order to successfully treat anemia in CKD with erythropoiesis-stimulating agentsand (ESA) and iron substitution, it is necessary to determine iron iron level. The diagnosis of iron deficiency anemia in patients with CKD is complicated due to the relatively low predictive ability of routine serum iron markers (e.g., ferritin and transferrin saturation) and more invasive measurements such as bone marrow iron stores. In the review novel biomarkers of iron metabolism are discussed such as hypoxia-inducible factor, erythroferon, growth differentiation factor 15 etc. with their possible clinical relevance.

Insulin resistance (IR) is characterised by increased gluconeogenesis in the liver and the resistance of peripheral receptors to insulin. Several factors, including IR, type 2 diabetes, new-onset diabetes after transplant (NODAT) and secondary parathyroidism, are related to chronic kidney disease (CKD). These factors are associated with higher mortality due to the increased risk of cardiovascular complications. Many factors have been identified as potential markers of IR in CKD. These factors include fibroblast growth factors (FGFs), a subfamily of endocrine polypeptides. In this study, we examined the association of FGF19, FGF21 and FGF23 with selected parameters related to carbohydrate metabolism and insulin resistance in non diabetic patients with predialysis CKD and in non diabetic patients after renal transplantation. The study included 108 non diabetic subjects: 40 patients with predialysis CKD, 45 patients with CKD who had undergone renal transplantation, and 23 healthy subjects (control group). In patients who had undergone renal transplantation, concentrations of FGF23 were increased compared to the control group and patients with predialysis CKD. The highest and lowest FGF19 concentrations were observed in CKD patients and in patients who had undergone kidney transplantation, respectively. This difference was statistically significant. Leptin concentrations were higher in CKD patients compared to the control group and patients who had undergone kidney transplantation. There were no statistically significant differences in adiponectin concentrations, lean body mass or fat tissue mass between the studied groups. HOMA-IR and insulin levels were significantly increased in CKD patients and in patients who had undergone renal transplantation in comparison to the control group. The results of the study suggest the involvement of FGF in carbohydrate metabolism and insulin resistance in patients with predialysis CKD, as well as a correlation with kidney function., Competing Interests: The authors report no conflicts of interest in this work.

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hematopoietic stem cell transplantation is a life-saving therapy for many patients with cancer, as well as patients with some nonmalignant hematologic disorders, such as aplastic anemia, sickle cell disease, and certain congenital immune deficiencies. Kidney injury directly associated with stem cell transplantation includes a wide range of structural and functional abnormalities, which may be vascular (hypertension, thrombotic microangiopathy), glomerular (albuminuria, nephrotic glomerulopathies), and/or tubulointerstitial. AKI occurs commonly after stem cell transplant, affecting 10%-73% of patients. The cause is often multifactorial and can include sepsis, nephrotoxic medications, marrow infusion syndrome, hepatic sinusoidal obstruction syndrome, thrombotic microangiopathy, infections, and graft versus host disease. The risk of post-transplant kidney injury varies depending on patient characteristics, type of transplant (allogeneic versus autologous), and choice of chemotherapeutic conditioning regimen (myeloablative versus nonmyeloablative). Importantly, AKI is associated with substantial morbidity, including the need for KRT in approximately 5% of patients and the development of CKD in up to 60% of transplant recipients. AKI has been associated universally with higher all-cause and nonrelapse mortality regardless of transplant type, and studies have consistently shown extremely high (>80%) mortality rates in those patients requiring acute dialysis. Accordingly, prevention, early recognition, and prompt treatment of kidney injury are essential to improving kidney and patient outcomes after hematopoietic stem cell transplantation, and for realizing the full potential of this therapy., (Copyright © 2020 by the American Society of Nephrology.)

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Anemia is a common manifestation of chronic kidney disease (CKD). The pathogenesis of CKD-associated anemia is multifactorial. Our understanding of the molecular control of iron metabolism has improved dramatically because of the discovery of hepcidin and attempts to introduce new drugs to stimulate erythropoiesis or affect the hepcidin-ferroportin pathway have recently emerged. Areas covered: We examine the possible role of hepcidin in iron metabolism and regulation and the potential therapeutic options involving hepcidin and hepcidin-ferroportin axis in renal anemia treatment. We focus on therapeutic targeting of hepcidin, the hepcidin-ferroportin axis and key molecules such as anti-hepcidin antibodies, spigelmers, and anticalins. We also discuss compounds affecting the bone morphogenetic protein receptor [BMP/BMPR] complex and molecules that influence hepcidin, such as hypoxia-inducible factor 1 stabilizers. Expert opinion: Hepcidin is a key regulator of iron availability and is a potential future therapeutic target for managing anemia that is associated with CKD. There are potential risks and benefits associated with novel sophisticated therapies and there are several novel options on the horizon; however, clinical data are currently limited and need development. Inhibition of hepcidin via various pathways might be a viable adjunctive therapeutic option in other clinical situations.

Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) is a major problem of public health. Currently, many of these patients experience progression of cardiovascular and renal disease, even when receiving optimal treatment. In previous years, several new drug classes for the treatment of type 2 DM have emerged, including inhibitors of renal sodium-glucose co-transporter-2 (SGLT-2) and glucagon-like peptide-1 (GLP-1) receptor agonists. Apart from reducing glycaemia, these classes were reported to have other beneficial effects for the cardiovascular and renal systems, such as weight loss and blood pressure reduction. Most importantly, in contrast to all previous studies with anti-diabetic agents, a series of recent randomized, placebo-controlled outcome trials showed that SGLT-2 inhibitors and GLP-1 receptor agonists are able to reduce cardiovascular events and all-cause mortality, as well as progression of renal disease, in patients with type 2 DM. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of SGLT-2 inhibitors and GLP-1 analogues, analyses the potential mechanisms involved in these actions and discusses their place in the treatment of patients with CKD and DM.

An increased risk of cardiovascular disease, independent of conventional risk factors, is present even at minor levels of renal impairment and is highest in patients with end-stage renal disease (ESRD) requiring dialysis. Renal dysfunction changes the level, composition and quality of blood lipids in favour of a more atherogenic profile. Patients with advanced chronic kidney disease (CKD) or ESRD have a characteristic lipid pattern of hypertriglyceridaemia and low HDL cholesterol levels but normal LDL cholesterol levels. In the general population, a clear relationship exists between LDL cholesterol and major atherosclerotic events. However, in patients with ESRD, LDL cholesterol shows a negative association with these outcomes at below average LDL cholesterol levels and a flat or weakly positive association with mortality at higher LDL cholesterol levels. Overall, the available data suggest that lowering of LDL cholesterol is beneficial for prevention of major atherosclerotic events in patients with CKD and in kidney transplant recipients but is not beneficial in patients requiring dialysis. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Lipid Management in CKD provides simple recommendations for the management of dyslipidaemia in patients with CKD and ESRD. However, emerging data and novel lipid-lowering therapies warrant some reappraisal of these recommendations.

Scientific societies are increasingly seen as central to the advancement of information sharing and collaboration among scientists and clinical investigators for the progress of medical research and the promotion of education, professional competence, integrity and quality studies. To more effectively serve the practicing nephrologists and investigators dedicated to renal science, the Council of the European Renal Association and European Dialysis and Transplantation Association (ERA-EDTA) reorganized and integrated the various activities of the society into two branches, the Clinical Nephrology Governance branch and the Renal Science branch. New affordable initiatives to promote research, education and professional development and to advocate for the recognition of chronic kidney disease as a major public health issue at the European level will be put in place and/or potentiated in the new organizational frame. Educational initiatives will be espoused to Continuous Professional Development and, starting from 2019, 14 Education & Continuous Professional Development courses will be held covering the full range of knowledge areas of modern nephrology. Consolidation and development is the short- and medium-term mantra of the ERA-EDTA. The society has a rich portfolio of successful activities and brilliant, creative scientists among its members. Integrating the various activities of the ERA-EDTA and treasuring the expertise and wisdom of its most accomplished members will facilitate collaborative research, education and its public impact at large.

The prevalence of chronic kidney disease (CKD) has increased markedly over past decades due to the aging of the worldwide population. Despite the progress in the prevention and treatment, the cardiovascular (CV) morbidity and mortality remain high among patients with CKD. Although CKD is a progressive and irreversible condition, it is possible to slow decreasing kidney function, as well as the development and progression of associated with kidney disease comorbidities. Diabetes mellitus has become major cause of CKD worldwide. It is estimated that the prevalence of diabetes will increase from 425 million worldwide in 2017 to 629 million by 2045, substantially the percentage of diabetic nephropathy among CKD patients is set to rise markedly. The results of multicenter trials concerning novel antidiabetic drugs suggest that efficacy in reducing CV risk is independent of the improvement in glycemic control. This review discusses underlying causes of high CV risk and strategies reducing individual burden among CKD patients.

Background/aims: Several studies have implicated atrial fibrillation (AF) as a contributing factor in chronic kidney disease (CKD) and cardiovascular events. The prevalence of coronary artery disease (CAD) in patients with AF varies substantially from 17% to 46.5%. There are only few studies concerning renal function in population with AF undergoing coronary angiography. The aim of the present study was to assess which type of AF is dominant in CKD population scheduled for coronary angiography and if it can influence patients' outcome, the association between renal impairment and the type of coronary procedures in AF patients and the influence of renal function on in-hospital mortality., Methods: We retrospectively studied 867 patients with AF hospitalized due to coronary angiography in two year time. The cut off value of CKD was eGFR ≤ 60 ml/min./1.73m2 evaluated by CKD-EPI formula., Results: A total of 867 patients with AF (44% women; mean age 72±10 years) were included in the analysis. The mean eGFR was 44±11ml/min./1.73m2 in patients with CKD and 89±18 ml/min./1.73m2 in patients with preserved renal function. Patients with CKD and AF were older (p< 0.001), had more often diabetes (p=0.009), heart failure (p< 0.001) and anaemia (p< 0.001). Patients with CKD and AF had more often permanent type of AF (p< 0.001). In CKD patients CHA2DS2VASc score was 4.3±1.5 and HAS-BLED score was 2.0±1.2 and it was significantly higher as compared to population with preserved renal function (p< 0.001, p=0.02, respectively). The use of oral anticoagulation was less frequent in CKD group (p< 0.001) although these patients had higher CHA2DS2VASc score. Patients with AF and CKD were more often admitted due to myocardial infarction (STEMI or NSTEMI) (p=0.02, p< 0.001, respectively) and more often underwent percutaneous coronary intervention (PCI) (p=0.01). Among coronary arteries the percutaneous coronary intervention (PCI) of left main artery was done more frequently in CKD patients (p=0.01). Among CKD population in-hospital mortality was significantly higher in patients with eGFR < 30 ml/min (p< 0.001)., Conclusion: Patients with CKD had more often permanent type of AF. Percutaneous interventions of the left main coronary artery, the only elective procedures influencing patients' prognosis, were done more frequently in CKD patients with AF. In-hospital mortality was significantly higher in patients with severe renal impairment. Despite the higher risk of ischaemic stroke in CKD group the use of oral anticoagulation therapy was significantly less frequent and the patients were deprived of the confirmed benefits of such treatment., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters., Methods: Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays., Results: Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin., Conclusions: Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.

Coronary artery disease and acute coronary syndrome (ACS) are both common in patients with chronic kidney disease (CKD). CKD patients have higher risks of bleeding and thrombosis. However, they remain under-represented in major randomized clinical trials (RCTs), and there is no medical evidence-based foundation on which to issue specific recommendations about the management of ACS in CKD. CKD patients with ACS frequently are diagnosed later, receive fewer acute interventions and are at increased risk of over-dosage of medications and under-prescription/under-performance of interventional treatments than CKD patients without ACS. The lack of RCTs should not discourage reliance on clinical common sense, while clearer decisional algorithms with better outcomes are a priority for urgent development. Future guidelines should further refine the assessment of CKD with ACS while placing much greater emphasis on the correct dosing of medications based on contemporaneous renal function. Until a strategy is designed with specific measures translated into the actual decrease of bleeding risk, providers will be forced to balance the equilibrium on a thin red line that is not clearly established., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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

Purpose: The aim of the study was to assess GDF-15 and iron status in patients in early stages of chronic kidney disease with a particular emphasis on elderly population in association of classic iron status parameters with novel iron homeostasis biomarkers and inflammatory parameters., Methods: Serum concentrations of GDF-15, iron (Fe), transferrin saturation, soluble transferrin receptor (sTfR), hepcidin, high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6), and hemoglobin were measured in 56 patients ≥65 years of age and in 31 <65 years of age., Results: In patients ≥65 years, serum concentrations of GDF-15 and hsCRP were significantly higher in comparison with younger group. There was no statistically significant difference in hemoglobin, iron, hepcidin, and sTfR concentration between the two studied groups. In both groups GDF-15 was significantly correlated with hemoglobin, eGFR, hsCRP, and IL-6. GDF-15 was significantly higher in patients with anemia in comparison with their non-anemic counterparts. In multivariate analysis, hemoglobin was found to be a predictor of log GDF-15 (beta value = 0.36, P = 0.006, R (2) = 37 %)., Conclusions: An intricate interplay between renal function, anemia, and GDF-15 concentrations awaits further studies, as there are few data regarding pathophysiological role of GDF-15 in diabetes, kidney disease, and other comorbidities. Further understanding regarding the signaling pathways of GDF-15 may help to discover next pieces in the exciting puzzle of GDF-15. Finally, as studies dealing with normal level of GDF-15 in the healthy aged are lacking, it is possible that the higher values of GDF-15 values found in the present study represent values of GDF-15 according to age more than CKD levels.

Cardiovascular diseases, including hypertension are the leading cause of death in the developed countries. Diabetes and chronic kidney disease became also more prevalent reaching almost the level of epidemy. Researchers are looking eagerly for the new risk and/or pathogenetic factors, as well as therapeutic option in these disease. It has been suggested that human kidney releases a protein named renalase into the bloodstream. It is supposed to be an enzyme which breaks down catecholamines in the blood circulation and regulate blood pressure. However, there were several doubts whether renalase exerts monoaminooxidase activity, or if it is monoaminooxidase at all. Recently, a hypothesis that it is also a cytokine was postulated. Studies on renalase polymorphisms in hypertension, cardiovascular disease or diabetes are inconsistent. Similarly, there are several discrepancies in the animal on the possible role of renalase in hypertension and cardiovascular diseases. Some studies report a protective role of renalase in acute kidney injury, whereas others showed that renalase levels were mainly dependent on kidney function, indicating rather a role of kidney in excretion of this substance. Moreover, validated assays are needed to evaluate renalase levels and activity. On one hand a deeper and more accurate link between renalase and cardiovascular diseases require further profound research, on the other hand whether or not renalase protein could be a new therapeutic target in these pathologies should also be considered. Whether renalase, discovered in 2005, might be a Holy Grail of hypertension, linking kidney and cardiovascular diseases, remains to be proven., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

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

The uremic syndrome is a complex mosaic of clinical alterations that may be attributable to one or more of these different solutes. Uremic symptoms in patients with chronic kidney disease are primarily a consequence of inadequate removal and subsequent accumulation of organic products normally metabolized or excreted by the kidney.

Background: Chronic kidney disease is almost always accompanied by anaemia. Erythropoietin-stimulating agents (ESA) can increase haemoglobin concentration and thus reduce the frequency of anaemia-related complications including the cardiovascular events., Aim: The aim of the study was to collect prospective data on 12-month standard ESA therapy used in haemodialyzed patients in selected CEE countries as well as on cardiovascular complications, iron status and anaemia treatment., Patients and Methods: Fifty centres in 3 countries participated in the study. A group of 398 haemodialysed stable patients (M-231, F-167) aged 19-90 years (57.5 ± 14.7) on standard ESA therapy for chronic renal anaemia were recruited. Twelve-month prospective data on iron parameters, ESA therapy and cardiovascular events were collected. The use of iron, folic acid and blood transfusions were also assessed. Patient were divided into three groups according to ESA therapy start: group A-patients who received ESA after start of haemodialysis, group B-patients who received ESA within 3 months from the day of first haemodialysis and group C-patients who had received ESA more than 3 months before haemodialysis. Chi(2) test for qualitative data and Kruskall-Wallis test for quantitative data with p < 0.05 were used in statistical analysis., Results: At prestudy period, the mean weekly dose of ESA in group C was statistically lower than in the remaining two groups (3,823 ± 3,169 vs. 5,276 ± 2,915 and 6,427 ± 3,441 units/week, p < 0.001), but during prospective phase of the study the doses did not differ among groups A, B and C. No major fluctuation of ESA administration schedule was observed during the study in the groups; however, at majority of visits, the mean frequency of ESA administration in group C was statistically higher than in groups A and B. At baseline visit, the haemoglobin concentration in group A patients (10.86 ± 1.34 g/dL) was slightly lower than in group B (11.26 ± 1.43 g/dL) and group C (10.98 ± 1.35 g/dL) (p = 0.025), but at subsequent visits these differences disappeared and mean haemoglobin concentration was stable around 11 g/dL. Ferritin concentration increased from 280 ± 241 at baseline to 506 ± 405 at month 12, and no important differences in the groups were observed. The other haematological parameters (haematocrit, iron concentration) remained stable during the entire study. The frequency of blood transfusion and total volume of blood in group C were lower than in groups A and B. During the prospective 12-month follow-up, 23 (5.8 %) of the patients died and 35 (8.8 %) were transplanted. No differences in death or transplantation rate were observed among groups A, B and C. The number of patients with adverse events, serious adverse events or drug-related adverse events in all groups was similar. In conclusion, ESA therapy increased haemoglobin concentration and no major differences in haematological parameters among the groups were observed during the entire study irrespective of early versus late start. Mortality, cardiovascular events or other adverse events were similar among the groups during the observation period; however, the limitation of the study is the sample size.

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

Introduction: The efficacy of statin treatment in chronic kidney disease (CKD) patients remains controversial. Therefore, we performed a meta-analysis to investigate whether statins modulate renal function in patients with CKD., Methods: Data from Scopus, PubMed, Web of Science, and the Cochrane Central Register of randomized controlled trials for years 1966-December 2012 were searched for appropriate studies., Results: Twenty trials with 6452 CKD subjects randomized to receive either statin or placebo were included. Statin therapy significantly influenced high sensitivity C-reactive protein levels in patients on or off dialysis [-0.28 mg/dl, 95%CI: -0.93 to -0.37; p<0.05 and -0.46 mg/dl, 95%CI: -0.87 to -0.05; p=0.03], respectively], urinary protein (-0.77 g/24 h, 95%CI: -1.24 to -0.29, p<0.02; this effect persisted for treatment ≤12 months), and serum creatinine but only for long-term therapy (3 years) (-0.65 mg/dl, 95%CI: -1.00 to -0.30; p=0.0003). The summary for standardized effect size of mean differences of glomerular filtration rate was 0.29 ml/min/1.73 m(2) (95%CI: 0.01 to 0.58; p=0.04), and depended on treatment duration - a significant increase was observed for between 1 and 3 years of statin therapy (0.50 ml/min/1.73 m(2), 95%CI: 0.40 to 0.60; p<0.0001), with no significant increase for both ≤1 and >3 years of the therapy., Conclusion: Statins might exert significant renoprotective effects in CKD patients; however, benefit may depend on the duration of treatment. This is an issue that warrants more definitive investigation. More studies are necessary in dialysis patients to credibly evaluate the renal effects of statin therapy., (© 2013.)

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.

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

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

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

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 10(13) endothelial cells weighing approximately 1kg, and covering a surface area of 4000 to 7000m(2) 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 2010 Elsevier B.V. All rights reserved.)

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.

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.