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Summary: Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

BackgroundWe determined the efficacy of free light chain (FLC) removal by regular dialysis equipment (high-flux filtration) with medium cutoff (MCO) membrane hemodialysis (HD) as an adjuvant treatment to standard chemotherapy for patients with acute kidney injury complicating multiple myeloma (MM) and its impact on further dialysis dependency.MethodsSixty patients with acute dialysis-dependent renal failure secondary to MM were treated with MCO-HD (55 patients) or HCO (high cutoff)-HD (5 patients) as a control. FLC serum concentration, total protein, immunoglobulins, and LDH were measured throughout the dialysis therapy. The kidney function of the patients was followed up for 1 year.ResultsThe median age was 69 years; 25 female and 35 male patients were enrolled. HD significantly reduced FLC kappa levels in the MCO/HCO group by 58%/84% (MCO/HCO group; p < 0.05) and FLC lambda by 39%/33% (MCO/HCO group; p < 0.05). Single HD data (MCO) showed a relative reduction of 70% in kappa and 37% in lambda FLC concentration, as expected by the different sizes of the light chains. Renal function improved significantly and continuously from starting creatinine 5.7/3.8 mg/dl (MCO/HCO group) before HD to 1.4/2.0 mg/dl (MCO/HCO group; p < 0.001) after 1 year. No significant alteration of total protein, immunoglobulins, and LDH concentrations by HD (HCO and MCO group) was observed. After 1 year, 37 of 60 patients were alive and 34 of them were off dialysis.ConclusionFLC elimination with MCO-HD is effective, technically easy, and less cost-intensive as compared with HCO-HD. Kidney function recovery in MM patients is achievable.

Abstract Background Right from the beginning of the SARS-CoV-2 pandemic the general public faced the challenge to find reliable and understandable information in the overwhelming flood of information. To enhance informed decision-making, evidence-based information should be provided. Aim was to explore the general public’s information needs and preferences on COVID-19 as well as the barriers to accessing evidence-based information. Methods We performed a cross-sectional study. Nine hundred twenty-seven panel members were invited to an online survey (12/2020-02/2021). The HeReCa-online-panel is installed at the Martin Luther University Halle-Wittenberg to assess regularly the general public’s view on health issues in five regions in Germany. The survey was set up in LimeSurvey, with nine items, multiple-choice and open-ended questions that allowed to gather qualitative data. Quantitative data were analysed descriptively and a content analysis was carried out to categorise the qualitative data. Results Six hundred thirty-six panel members provided data; mean age 52 years, 56.2% female, and 64.9% with higher education qualifications. Asked about relevant topics related to COVID-19, most participants selected vaccination (63.8%), infection control (52%), and long-term effects (47.8%). The following 11 categories were derived from the qualitative analysis representing the topics of interest: vaccination, infection control, long-term effects, therapies, test methods, mental health, symptoms, structures for pandemic control, infrastructure in health care, research. Participants preferred traditional media (TV 70.6%; radio 58.5%; newspaper 32.7%) to social media, but also used the internet as sources of information, becoming aware of new information on websites (28.5%) or via email/newsletter (20.1%). The knowledge question (Which European country is most affected by the SARS-CoV-2 pandemic?) was correctly answered by 7.5% of participants. The Robert Koch Institute (93.7%) and the World Health Organization (78%) were well known, while other organisations providing health information were rarely known (

Abstract Extended cut-off filtration by medium cut-off membranes (MCO) has been shown to be safe in maintenance hemodialysis (HD). The notion of using them for the control of chronic low-grade inflammation and positively influencing cellular immune aberrations seems tempting. We conducted an open label, multicenter, randomized, 90 day 2-phase cross over clinical trial (MCO- vs. high flux-HD). 46 patients underwent randomization of which 34 completed the study. Dialysate- or pre- and post-dialysis serum inflammatory mediators were assayed for each study visit. Ex vivo T cell activation was assessed from cryopreserved leucocytes by flow cytometry. Linear mixed models were used to compare treatment modalities, with difference in pre-dialysis serum MCP-1 levels after 3 months as the predefined primary endpoint. Filtration/dialysate concentrations of most mediators, including MCP-1 (mean ± SD: 10.5 ± 5.9 vs. 5.1 ± 3.8 pg/ml, P

BackgroundKidney transplant recipients (KTRs) are at high risk for a severe course of coronavirus disease 2019 (COVID-19); thus, effective vaccination is critical. However, the achievement of protective immunogenicity is hampered by immunosuppressive therapies. We assessed cellular and humoral immunity and breakthrough infection rates in KTRs vaccinated with homologous and heterologous COVID-19 vaccination regimens.MethodWe performed a comparative in-depth analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific T-cell responses using multiplex Fluorospot assays and SARS-CoV-2-specific neutralizing antibodies (NAbs) between three-times homologously (n = 18) and heterologously (n = 8) vaccinated KTRs.ResultsWe detected SARS-CoV-2-reactive T cells in 100% of KTRs upon third vaccination, with comparable frequencies, T-cell expression profiles, and relative interferon γ and interleukin 2 production per single cell between homologously and heterologously vaccinated KTRs. SARS-CoV-2-specific NAb positivity rates were significantly higher in heterologously (87.5%) compared to homologously vaccinated (50.0%) KTRs (P < 0.0001), whereas the magnitudes of NAb titers were comparable between both subcohorts after third vaccination. SARS-CoV-2 breakthrough infections occurred in equal numbers in homologously (38.9%) and heterologously (37.5%) vaccinated KTRs with mild-to-moderate courses of COVID-19.ConclusionOur data support a more comprehensive assessment of not only humoral but also cellular SARS-CoV-2-specific immunity in KTRs to provide an in-depth understanding about the COVID-19 vaccine–induced immune response in a transplant setting.

X-linked Alport syndrome (AS) caused by hemizygous disease-causing variants in COL4A5 primarily affects males. Females with a heterozygous state show a diverse phenotypic spectrum ranging from microscopic hematuria to end-stage kidney disease (ESKD) and extrarenal manifestations. In other X-linked diseases, skewed X-inactivation leads to preferential silencing of one X-chromosome and thus can determine the phenotype in females. We aimed to show a correlation between X-inactivation in blood and urine-derived renal cells and clinical phenotype of females with a heterozygous disease-causing variant in COL4A5 compared to healthy controls. A total of 56 females with a heterozygous disease-causing COL4A5 variant and a mean age of 31.6 ± 18.3 SD years were included in this study. A total of 94% had hematuria, 62% proteinuria >200 mg/day, yet only 7% had decreased eGFR. Using human androgen receptor assay X-inactivation was examined in blood cells of all 56 individuals, in urine-derived cells of 27 of these individuals and in all healthy controls. X-inactivation did not correlate with age of first manifestation, proteinuria or eGFR neither in blood, nor in urine. The degree of X-inactivation showed a moderate association with age, especially in urine-derived cells of the patient cohort (rho = 0.403, p = 0.037). Determination of X-inactivation allelity revealed a shift of X-inactivation toward the COL4A5 variant bearing allele. This is the first study examining X-inactivation of urine-derived cells from female individuals with AS. A correlation between phenotype and X-inactivation could not be observed suspecting other genetic modifiers shaping the phenotype in female individuals with AS. The association of X-inactivation with age in urine-derived cells suggests an escape-mechanism inactivating the COL4A5 variant carrying allele in female individuals with AS.

Disease-causing variants in COL4A3-5 are associated with type-IV-collagen-related nephropathy, a genetically and phenotypically multifaceted disorder comprising Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) and autosomal, X-linked and a proposed digenic inheritance. Initial symptoms of individuals with AS are microscopic hematuria followed by proteinuria leading to kidney failure (90% on dialysis < age 40 years). In contrast, individuals with TBMN, an outdated histology-derived term, present with microscopic hematuria, only some of them develop kidney failure (>50 years of age). An early diagnosis of type-IV-collagen-related nephropathy is essential for optimized therapy and slowing of the disease. Sixty index cases, in whom exome sequencing had been performed and with disease-causing variant(s) in COL4A3-5, were evaluated concerning their clinical tentative diagnosis and their genotype. Of 60 reevaluated individuals with type-IV-collagen-related nephropathy, 72% had AS, 23% TBMN and 5% focal segmental glomerulosclerosis (FSGS) as clinical tentative diagnosis. The FSGS cases had to be re-classified as having type-IV-collagen-related nephropathy. Twelve percent of cases had AS as clinical tentative diagnosis and a monoallelic disease-causing variant in COL4A3/4 but could not be classified as autosomal dominant AS because of limited or conflicting clinical data. This study illustrates the complex clinical and genetic picture of individuals with a type IV-collagen-related nephropathy indicating the need of a refined nomenclature and the more interdisciplinary teamwork of clinicians and geneticists as the key to optimized patient care.

Abstract Objective Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age‐matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels. Methods 152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions. Results In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained. Conclusion This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.

Abstract Cohort studies often provide a large array of data on study participants. The techniques of statistical learning can allow an efficient way to analyze large datasets in order to uncover previously unknown, clinically relevant predictors of morbidity or mortality. We applied a combination of elastic net penalized Cox regression and stability selection with the aim of identifying novel predictors of mortality in a cohort of prevalent hemodialysis patients. In our analysis we included 475 patients from the “rISk strAtification in end-stage Renal disease” (ISAR) study, who we split into derivation and confirmation cohorts. A wide array of examinations was available for study participants, resulting in over a hundred potential predictors. In the selection approach many of the well established predictors were retrieved in the derivation cohort. Additionally, the serum levels of IL-12p70 and AST were selected as mortality predictors and confirmed in the withheld subgroup. High IL-12p70 levels were specifically prognostic of infection-related mortality. In summary, we demonstrate an approach how statistical learning can be applied to a cohort study to derive novel hypotheses in a data-driven way. Our results suggest a novel role of IL-12p70 in infection-related mortality, while AST is a promising additional biomarker in patients undergoing hemodialysis.

Background: Atrial fibrillation (AF) is common in hemodialysis patients and contributes to increased mortality. We aimed to examine heart rate variability triangular index (HRVI) in hemodialysis patients with AF as it has recently been reported to predict mortality in AF patients without kidney disease.Methods: A total of 88 patients on hemodialysis with a medical history of AF or newly diagnosed AF underwent 24-h electrocardiography recordings. The primary endpoint of cardiovascular mortality was recorded during a median follow up of 3.0 years. Risk prediction was assessed by Cox regression, both unadjusted and adjusted for the Charlson Comorbidity Index and the Cardiovascular Mortality Risk Score.Results: Median age was 76 years, median dialysis vintage was 27 months. Altogether, 22 and 44 patients died due to cardiovascular and non-cardiovascular causes. In 55% of patients AF was present during the recording. Kaplan-Meier plots of HRVI quartiles suggested a non-linear association between HRVI, cardiovascular, and all-cause mortality which was confirmed in non-linear Cox regression analysis. Adjusted linear Cox regression revealed a hazard ratio of 6.2 (95% CI: 2.1–17.7, p = 0.001) and 2.2 (95% CI: 1.3–3.8, p = 0.002) for the outer quartiles (combined first and fourth quartile) for cardiovascular and all-cause mortality, respectively. Patients in the first quartile were more likely to have sinus rhythm whereas patients in the fourth quartile were more likely to have AF.Conclusions: We found a U-shaped association between HRVI and mortality in hemodialysis AF patients. The results might contribute to risk stratification independent of known risk scores in hemodialysis AF patients.

Background: Chronic kidney disease (CKD) in childhood and adolescence occurs with a median incidence of 9 per million of the age-related population. Over 70% of CKD cases under the age of 25 years can be attributed to a hereditary kidney disease. Among these are hereditary podocytopathies, ciliopathies and (monogenic) congenital anomalies of the kidney and urinary tract (CAKUT). These disease entities can present with a vast variety of extrarenal manifestations. So far, skeletal anomalies (SA) have been infrequently described as extrarenal manifestation in these entities. The aim of this study was to retrospectively investigate a cohort of individuals with hereditary podocytopathies, ciliopathies or CAKUT, in which molecular genetic testing had been performed, for the extrarenal manifestation of SA.Material and Methods: A cohort of 65 unrelated individuals with a clinically presumed hereditary podocytopathy (focal segmental glomerulosclerosis, steroid resistant nephrotic syndrome), ciliopathy (nephronophthisis, Bardet-Biedl syndrome, autosomal recessive/dominant polycystic kidney disease), or CAKUT was screened for SA. Data was acquired using a standardized questionnaire and medical reports. 57/65 (88%) of the index cases were analyzed using exome sequencing (ES).Results: 8/65 (12%) index individuals presented with a hereditary podocytopathy, ciliopathy, or CAKUT and an additional skeletal phenotype. In 5/8 families (63%), pathogenic variants in known disease-associated genes (1x BBS1, 1x MAFB, 2x PBX1, 1x SIX2) could be identified.Conclusions: This study highlights the genetic heterogeneity and clinical variability of hereditary nephropathies in respect of skeletal anomalies as extrarenal manifestation.

Mineralocorticoid-receptor (MR) dysfunction as expressed by low systolic blood pressure and a high salivary aldosterone/cortisol ratio predicts less favorable antidepressant treatment outcome. Inhibition of peripheral 11-beta-hydroxysteroid-dehydrogenase type 2 (11betaHSD2) reverses these markers. We therefore tested the hypothesis that the 11betaHSD2 inhibitor glycyrrhizin affects treatment outcome via this mechanism. We administered Glycyrrhiza glabra (GG) extract containing 7–8 % of glycyrrhizin at a dose of 2 × 700 mg daily adjunct to standard antidepressants in hospitalized patients with major depression. These subjects were compared in an open-label fashion with patients, who did not receive GG (treatment as usual, TAU). Assessments were done at baseline and approximately 2 weeks after. Twelve subjects were treated with GG and compared to 55 subjects with TAU. At week 2, the Hamilton Depression Rating Scale (HAMD-21) change from baseline as well as the CGI-S change showed a significant time × treatment interaction (p < 0.03), indicating a possible therapeutic benefit of GG. Clinical benefit seems to be more pronounced in subjects with lower systolic blood pressure and significantly correlated with reduced sleep duration in the GG group. Our preliminary data show that treatment with the 11betaHSD2 inhibitor glycyrrhizin may possess a beneficial effect on antidepressant response, which may be specific to a defined depression subtype.

(1) Background: Health care workers (HCWs) play a key role in increasing anti-COVID vaccination rates. Fear of potential side effects is one of the main reasons for vaccine hesitancy. We investigated which side effects are of concern to HCWs and how these are associated with vaccine hesitancy. (2) Methods: Data were collected in an online survey in February 2021 among HCWs from across Germany with 4500 included participants. Free-text comments on previously experienced vaccination side effects, and fear of short- and long-term side effects of the COVID-19 vaccination were categorized and analyzed. (3) Results: Most feared short-term side effects were vaccination reactions, allergic reactions, and limitations in daily life. Most feared long-term side effects were (auto-) immune reactions, neurological side effects, and currently unknown long-term consequences. Concerns about serious vaccination side effects were associated with vaccination refusal. There was a clear association between refusal of COVID-19 vaccination in one’s personal environment and fear of side effects. (4) Conclusions: Transparent information about vaccine side effects is needed, especially for HCW. Especially when the participants’ acquaintances advised against vaccination, they were significantly more likely to fear side effects. Thus, further education of HCW is necessary to achieve good information transfer in clusters as well.

BackgroundExcess mortality in hemodialysis patients is mostly of cardiovascular origin. We examined the association of heart rate turbulence (HRT), a marker of baroreflex sensitivity, with cardiovascular mortality in hemodialysis patients.MethodsA population of 290 prevalent hemodialysis patients was followed up for a median of 3 years. HRT categories 0 (both turbulence onset [TO] and slope [TS] normal), 1 (TO or TS abnormal), and 2 (both TO and TS abnormal) were obtained from 24 h Holter recordings. The primary end-point was cardiovascular mortality. Associations of HRT categories with the endpoints were analyzed by multivariable Cox regression models including HRT, age, albumin, and the improved Charlson Comorbidity Index for hemodialysis patients. Multivariable linear regression analysis identified factors associated with TO and TS.ResultsDuring the follow-up period, 20 patients died from cardiovascular causes. In patients with HRT categories 0, 1 and 2, cardiovascular mortality was 1, 10, and 22%, respectively. HRT category 2 showed the strongest independent association with cardiovascular mortality with a hazard ratio of 19.3 (95% confidence interval: 3.69–92.03; P < 0.001). Age, calcium phosphate product, and smoking status were associated with TO and TS. Diabetes mellitus and diastolic blood pressure were only associated with TS.ConclusionIndependent of known risk factors, HRT assessment allows identification of hemodialysis patients with low, intermediate, and high risk of cardiovascular mortality. Future prospective studies are needed to translate risk prediction into risk reduction in hemodialysis patients.

Background: Alport syndrome (AS) is a progressive kidney disorder leading to end stage renal disease (ESRD). Extrarenal symptoms like hearing loss and ocular changes can be observed. Approximately 85% of the patients carry pathogenic variants in COL4A5 (X-linked inheritance). The variant c.1871G>A, p.(Gly624Asp) in COL4A5 is described in the literature as a hypomorphic variant associated with thin basement membrane nephropathy (TBMN). ESRD was only seen rarely at a median age of 50 years and extrarenal manifestations have only been described in single cases.Case report and Methods: This is a report on a family with X-linked AS. In the female index patient, microscopic hematuria, and proteinuria were observed beginning at the age of 20 years and 41 years, respectively. Microscopic hematuria was also present in the daughter (from 6th month of life), the son (from 22nd month of life), the mother and the maternal grandniece. Proteinuria was observed in the maternal aunt and paternal grandmother. The father of the index patient, a paternal uncle and a second cousin presented with ESRD at the age of 49, 34, and 70 years of life, respectively. Extrarenal manifestations were absent in the whole family. In the index patient, her children and her mother molecular diagnostics were performed using Sanger and exome sequencing.Results: In all examined family members the variant c.1871G>A, p.(Gly624Asp) in COL4A5 was identified. With the exception of the index patient, who was homozygous for this variant, all family members carried the variant heterozygously, or hemizygously. A different or additional monogenic hereditary nephropathy could not be detected by exome sequencing of the index patient.Discussion: This is the first report of a patient with the variant p.(Gly624Asp) in COL4A5 in a homozygous state. The variant was previously reported as a mild variant requiring dialysis in less than 10%. The family presented, however, with a more severe clinical course. We therefore suggest to question the term “hypomorphic” in the context of the variant p.(Gly624Asp) although molecular diagnostics could not be done in all affected family members.

Background: Association of Ambulatory Blood Pressure Monitoring (ABPM) with mortality depends on cardiac function in hemodialysis patients. Evidence for the predictive power of central Systolic Pressure (cSBP) is inconclusive. Thus, this study aimed to investigate the additional information of ambulatory cSBP in risk prediction in a cohort of hemodialysis patients. Methods: Within the ISAR-study cohort, 344 hemodialysis patients underwent 24 h ABPM on the dialysis day. All-cause and cardiovascular mortality served as endpoints. Risk prediction was performed using Cox regression in patients with or without atrial fibrillation (AF) or heart failure (HF) for peripheral (pSBP) and central systolic pressure calibrated with peripheral systolic and diastolic pressure (cSBP1) or peripheral mean and diastolic pressure (cSBP2). Results: During a mean follow-up of 37.6 (17.5 SD) months, 115 patients died, of whom 47 due to cardiovascular reasons. In patients with AF or HF, a negative association to mortality could be observed, independent of pressure location and calibration (see Table). In patients without AF or HF, these associations were to the opposite directions and cSBP2 was superior to pSBP and cSBP1 for all-cause (pSBP: HR = 1.01, p = 0.30; cSBP1: HR = 1.00, p = 0.77; cSBP2: HR = 1.01, p = 0.06) and cardiovascular (pSBP: HR =1.03, p = 0.02; cSBP1: HR = 1.02, p = 0.06; cSBP2: HR = 1.03, p = 0.003) mortality. This circumstance was confirmed in multivariable analysis combining pSBP and differences between pSBP and cSBP (see Table). Conclusions: This study provides evidence for the additional information of central systolic blood pressure and its dependency on calibration in risk prediction in hemodialysis patients. Further studies are needed to confirm these findings.

Introduction: Steroid-resistant nephrotic syndrome (SRNS) is one of the most frequent causes for chronic kidney disease in childhood. In ~30% of these cases a genetic cause can be identified. The histological finding in SRNS is often focal segmental glomerulosclerosis (FSGS). In rare cases, however, pathogenic variants in genes associated with Alport syndrome can be identified in patients with the histological finding of FSGS.Materials and Methods: Clinical information was collected out of clinical reports and medical history. Focused molecular genetic analysis included sequencing of COL4A5 and COL4A3 in the index patient. Segregation analysis of identified variants was performed in the parents and children of the index patient.Results: The female index patient developed mild proteinuria and microscopic hematuria in childhood (12 years of age). The histological examination of the kidney biopsies performed at the age of 21, 28, and 32 years showed findings partly compatible with FSGS. However, immunosuppressive treatment of the index patient did not lead to a sufficient reduction of in part nephrotic-range proteinuria. After the patient developed hearing impairment at the age of 34 years and her daughter was diagnosed with microscopic hematuria at the age of 6 years, re-examination of the index's kidney biopsies by electron microscopy revealed textural changes of glomerular basement membrane compatible with Alport syndrome. Molecular genetic analysis identified two missense variants in COL4A3 in a compound heterozygous state with maternal and paternal inheritance. One of them is a novel variant that was also found in the 6 year old daughter of the index patient who presented with microscopic hematuria.Discussion: We were able to show that a novel variant combined with a previously described variant in compound heterozygous state resulted in a phenotype that was histologically associated with FSGS. Molecular genetic analysis therefore can be essential to solve difficult cases that show an unusual appearance and therefore improve diagnostic accuracy. Additionally, unnecessary and inefficient treatment with multiple side effects can be avoided.

Heart rate variability (HRV) analysis is a non-invasive tool for assessing cardiac health. Entropy measures quantify the chaotic properties of HRV, but they are sensitive to the choice of their required parameters. Previous studies therefore have performed parameter optimization, targeting solely their particular patient cohort. In contrast, this work aimed to challenge entropy measures with recently published parameter sets, without time-consuming optimization, for risk prediction in end-stage renal disease patients. Approximate entropy, sample entropy, fuzzy entropy, fuzzy measure entropy, and corrected approximate entropy were examined. In total, 265 hemodialysis patients from the ISAR (rISk strAtification in end-stage Renal disease) study were analyzed. Throughout a median follow-up time of 43 months, 70 patients died. Fuzzy entropy and corrected approximate entropy (CApEn) provided significant hazard ratios, which remained significant after adjustment for clinical risk factors from literature if an entropy maximizing threshold parameter was chosen. Revealing results were seen in the subgroup of patients with heart disease (HD) when setting the radius to a multiple of the data’s standard deviation ( r = 0.2 · σ ); all entropies, except CApEn, predicted mortality significantly and remained significant after adjustment. Therefore, these two parameter settings seem to reflect different cardiac properties. This work shows the potential of entropy measures for cardiovascular risk stratification in cohorts the parameters were not optimized for, and it provides additional insights into the parameter choice.

Background: Although low magnesium levels have been associated with an increased mortality in dialysis patients, they are kept low by routinely-used dialysates containing 0.50 mmol/L magnesium. Thus, we investigated the impact of a higher dialysate magnesium concentration on mortality. Methods: 25 patients on high dialysate magnesium (HDM) of 0.75 mmol/L were 1:2 matched to 50 patients on low dialysate magnesium (LDM) of 0.50 mmol/L and followed up for 3 years with regards to all-cause and cardiovascular mortality. Patients were matched according to age, gender, a modified version of the Charlson Comorbidity Index (CCI), and smoking status. Results: During the follow-up period, five patients died in the HDM and 18 patients in the LDM group. Patients in the HDM group had significantly higher ionized serum magnesium levels than matched controls (0.64 ± 0.12 mmol/L vs. 0.57 ± 0.10 mmol/L, p = 0.034). Log rank test showed no difference between treatment groups for all-cause mortality. After adjustment for age and CCI, Cox proportional hazards regression showed that HDM independently predicted a 65% risk reduction for all-cause mortality (hazard ratio 0.35, 95% confidence interval [CI]: 0.13, 0.97). Estimated 3-year probability of death from a cardiovascular event was 14.5% (95% CI: 7.9, 25.8) in the LDM group vs. 0% in the HDM group. Log rank test found a significant group difference for cardiovascular mortality (χ2 = 4.15, p = 0.042). Conclusions: Our data suggests that there might be a beneficial effect of an increased dialysate magnesium on cardiovascular mortality in chronic dialysis patients.

An important tool in early diagnosis of cardiac dysfunctions is the analysis of electrocardiograms (ECGs) obtained from ambulatory long-term recordings. Heart rate variability (HRV) analysis became a significant tool for assessing the cardiac health. The usefulness of HRV assessment for the prediction of cardiovascular events in end-stage renal disease patients was previously reported. The aim of this work is to verify an enhanced algorithm to obtain an RR-interval time series in a fully automated manner. The multi-lead corrected R-peaks of each ECG lead are used for RR-series computation and the algorithm is verified by a comparison with manually reviewed reference RR-time series. Twenty-four hour 12-lead ECG recordings of 339 end-stage renal disease patients from the ISAR (rISk strAtification in end-stage Renal disease) study were used. Seven universal indicators were calculated to allow for a generalization of the comparison results. The median score of the indicator of synchronization, i.e. intraclass correlation coefficient, was 96.4% and the median of the root mean square error of the difference time series was 7.5 ms. The negligible error and high synchronization rate indicate high similarity and verified the agreement between the fully automated RR-interval series calculated with the AIT Multi-Lead ECGsolver and the reference time series. As a future perspective, HRV parameters calculated on this RR-time series can be evaluated in longitudinal studies to ensure clinical benefit. [ABSTRACT FROM AUTHOR]