Mortality prediction in stable hemodialysis patients is refined by YKL-40, a 40-kDa glycoprotein associated with inflammation.

Chronic inflammation contributes to increased mortality in hemodialysis (HD) patients. YKL-40 is a novel marker of inflammation, tissue remodeling, and highly expressed in macrophages inside vascular lesions. Elevated levels of YKL-40 have been reported for HD patients but how it integrates into the proinflammatory mediator network as a predictor of mortality remains elusive. We studied serum YKL-40, Interleukin-6 (IL-6), high-sensitivity C-reactive protein, monocyte chemotactic protein-1 (MCP-1), and interferon-gamma induced protein-10 (IP-10) in 475 chronic hemodialysis patients. Patients were followed for mortality for a median of 37 [interquartile range: 25-49] months and checked for interrelation of the measured mediators. To plot cumulative incidence functions, patients were stratified into terciles per YKL-40, IL-6, MCP-1, and IP-10 levels. Multivariable Cox regression models were built to examine associations of YKL-40, IP-10, and MCP-1 with all-cause and cause-specific mortality. Net reclassification improvement was calculated for the final models containing YKL-40 and IL-6. Increased YKL-40 was independently associated with age, IP-10, and IL-6 serum levels. After adjustment for demographic and laboratory parameters, comorbidities, and IL-6, only YKL-40 significantly improved risk prediction for all-cause (hazard ratio 1.4; 95% confidence interval 1.1-1.8) and cardiovascular mortality (hazard ratio 1.5; 95% confidence interval 1.03-2.2). Thus, in contrast to other biomarkers of aberrant macrophage activation, YKL-40 reflects inflammatory activity, which is not covered by IL-6. Mechanistic and prospective studies are needed to test for causal involvement of YKL-40 and whether it might qualify as a therapeutic target.

A novel citrate-based protocol versus heparin anticoagulation for sustained low-efficiency dialysis in the ICU: safety, efficacy, and cost.

BACKGROUND: The high cost, complexity of the available protocols, and metabolic complications are the major barriers that impede the clinical utilization of regional citrate anticoagulation (RCA) for sustained low efficiency dialysis (SLED) in critically ill patients. By comparing a novel protocol for SLED using 30% citrate solution with common protocol using unfractionated heparin, this study aimed to provide new insights for clinical applications of RCA. METHODS: In this retrospective study, a total of 282 critically ill patients who underwent SLED with citrate and/or heparin anticoagulation in six adult ICUs were enrolled. These patients were divided into three groups based on the anticoagulation regimens they had received during the treatment in ICU: Group 1 (Citrate) had only received treatment with citrate anticoagulation (n=75); Group 2 (Heparin) only with heparin anticoagulation (n=79); and Group 3 (Both) with both citrate and heparin anticoagulation (n=128). We compared the mortality, metabolic complications as well as cost among these groups using different anticoagulation regimens. RESULTS: The in-hospital mortality did not significantly differ among groups (p> 0.1). However, three patients in heparin group suffered from severe bleeding which led to death, while none in citrate group. Overall, 976 SLED sessions with heparin anticoagulation and 808 with citrate were analyzed. The incidence of extracorporeal circuit clotting was significantly less in citrate (5%), as compared to that in heparin (10%) (p< 0.001). Metabolic complications and hypotension which led to interruption of SLED occurred more frequently, though not significantly, in citrate (p= 0.06, p= 0.23). Furthermore, with 30% citrate solution, the cost of anticoagulant was reduced by 70% in comparison to previously reported protocol using Acid Citrate Dextrose solution A (ACD-A). CONCLUSIONS: Our results indicated that anticoagulation regimens for SLED did not significantly affect the mortality of patients. Citrate anticoagulation was superior to heparin in preventing severe bleeding and circuit clotting. The protocol adopted in this study using 30% citrate solution was safe as well as efficacious. In the meantime, it was much more cost-efficient than other citrate-based protocol.

Pulse wave velocity is associated with cognitive impairment in hemodialysis patients.

Cognitive impairment in hemodialysis patients is common and associated with adverse outcomes. So far, the underlying pathogenesis remains unclear. Therefore, we examined the potential relationship between cognitive impairment and three different categories of risk factors with particular focus on arterial stiffness measured by pulse wave velocity (PWV). A total of 201 chronic hemodialysis patients underwent cognitive testing under standardized conditions using the Montreal Cognitive Assessment (MoCA). Demographic data including cardiovascular risk factors, dialysis-associated factors as well as factors related to chronic kidney disease (CKD) were analyzed. To account for arterial stiffness, PWV was measured by ambulatory blood pressure monitoried with an oscillometric device that records brachial blood pressure along with pulse waves. In our cohort, 60.2% of patients showed pathological MoCA test results indicating cognitive impairment. PWV was significantly associated with cognitive impairment apart from age, educational level, diabetes, and hypercholesterolemia. High prevalence of cognitive impairment in hemodialysis patients was confirmed. For the first time, an association between cognitive impairment and arterial stiffness was detected in a larger cohort of hemodialysis patients. Concerning the underlying pathogenesis of cognitive impairment, current results revealed a potential involvement of arterial stiffness, which has to be further evaluated in future studies.

Rationale and study design of the prospective, longitudinal, observational cohort study "rISk strAtification in end-stage renal disease" (ISAR) study.

BACKGROUND: The ISAR study is a prospective, longitudinal, observational cohort study to improve the cardiovascular risk stratification in endstage renal disease (ESRD). The major goal is to characterize the cardiovascular phenotype of the study subjects, namely alterations in micro- and macrocirculation and to determine autonomic function. METHODS/DESIGN: We intend to recruit 500 prevalent dialysis patients in 17 centers in Munich and the surrounding area. Baseline examinations include: (1) biochemistry, (2) 24-h Holter Electrocardiography (ECG) recordings, (3) 24-h ambulatory blood pressure measurement (ABPM), (4) 24 h pulse wave analysis (PWA) and pulse wave velocity (PWV), (5) retinal vessel analysis (RVA) and (6) neurocognitive testing. After 24 months biochemistry and determination of single PWA, single PWV and neurocognitive testing are repeated. Patients will be followed up to 6 years for (1) hospitalizations, (2) cardiovascular and (3) non-cardiovascular events and (4) cardiovascular and (5) all-cause mortality. DISCUSSION/CONCLUSION: We aim to create a complex dataset to answer questions about the insufficiently understood pathophysiology leading to excessively high cardiovascular and non-cardiovascular mortality in dialysis patients. Finally we hope to improve cardiovascular risk stratification in comparison to the use of classical and non-classical (dialysis-associated) risk factors and other models of risk stratification in ESRD patients by building a multivariable Cox-Regression model using a combination of the parameters measured in the study. CLINICAL TRIALS IDENTIFIER: ClinicalTrials.gov NCT01152892 (June 28, 2010).

Diminished Short- and Long-Term Antibody Response after SARS-CoV-2 Vaccination in Hemodialysis Patients.

Short-term studies have shown an attenuated immune response in hemodialysis patients after COVID-19-vaccination. The present study examines how antibody response is maintained after vaccination against SARS-CoV-2 in a large population of hemodialysis patients from six outpatient dialysis centers. We retrospectively assessed serum antibody levels against SARS-CoV-2 spike protein and nucleocapsid protein (electrochemiluminescence immunoassays, Roche Diagnostics) after COVID-19-vaccination in 298 hemodialysis and 103 non-dialysis patients (controls), comparing early and late antibody response. Compared to a non-dialysis cohort hemodialysis patients showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up measurement (median 6 months after vaccination). Significantly more hemodialysis patients had anti-SARS-CoV-2-S antibody titers below 100 U/mL (p < 0.001), which increased during follow-up from 23% to 45% but remained low in the control group (3% vs. 7%). In multivariate analysis, previous COVID-19 infections (p < 0.001) and female gender (p < 0.05) were significantly associated with higher early as well as late antibody vaccine response in hemodialysis patients, while there was a significant inverse correlation between patient age and systemic immunosuppression (p < 0.001). The early and late antibody responses were significantly higher in patients receiving vaccination after a SARS-CoV-2 infection compared to uninfected patients in both groups (p < 0.05). We also note that a higher titer after complete immunization positively affected late antibody response. The observation, that hemodialysis patients showed a significantly stronger decline of SARS-CoV-2 vaccination antibody titers within 6 months, compared to controls, supports the need for booster vaccinations to foster a stronger and more persistent antibody response.

Reduced Mortality in Maintenance Haemodialysis Patients on High versus Low Dialysate Magnesium: A Pilot Study.

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.

Cognitive impairment in hemodialysis patients: Implementation of cut-off values for the Montreal Cognitive Assessment (MoCA)-test for feasible screening.

OBJECTIVE: Reliable identification of cognitive impairment in hemodialysis patients is of utmost importance, as it is associated with poor outcomes including dialysis withdrawal and death. High prevalence of cognitive impairment has been demonstrated in several studies using brief screening instruments or neuropsychological test batteries. However, the relevance of cognitive impairment as well as the accuracy of screening procedures have never been studied in this patient population. METHODS: 151 chronic hemodialysis patients (mean age 65.78 ± 14.88 years, 73,5% male) underwent cognitive testing under standardized conditions by the Montreal Cognitive Assessment (MoCA) and, in a second step, the Clinical Dementia Rating scale (CDR), an international standard to measure the severity of dementia. For calculating MoCA cut-off values on the basis of the CDR global score, receiver operator characteristics (ROC) analysis and c-statistic were applied. RESULTS: 49.0% of patients were categorized as 0.5 in the CDR global with memory being the predominantly affected domain (47.7% of patients scored ≥ 0.5). Youden's Index led to a threshold of 23.5 points for the MoCA test for optimal differentiation between cognitively normal (CDR global < 0.5) and impaired patients (CDR global ≥ 0.5) based on a sensitivity of approximately 99% and a specificity of approximately 74%. CONCLUSION: Interference of cognitive impairment with patients' independence and daily life was shown using the CDR for the first time in hemodialysis patients. A MoCA score of 23.5 points turned out as optimal threshold to differentiate between patients with and without functional impairment in the CDR, thereby paving the way for implementation of the MoCA test as a quick and thus highly feasible screening instrument for periodic testing in clinical routine.

Aortic pulse wave velocity predicts mortality in chronic kidney disease stages 2-4.

BACKGROUND: Chronic kidney disease (CKD) is characterized by aortic stiffness and increased cardiovascular mortality. In end-stage renal disease, aortic stiffness predicts mortality, whereas this role remains uncertain in mild-to-moderate CKD. We aimed to investigate whether aortic pulse wave velocity (aPWV) predicts mortality and renal disease progression in CKD patients. METHODS: We enrolled 135 CKD patients stages 2-4 [estimated glomerular filtration rate (eGFR): 41.1 (28.5-61.6) ml/min per 1.73  m] in the study and assessed aPWV. The combined renal end-point was defined as at least 50% decline in renal function and/or start of renal replacement therapy. RESULTS: During the observational period of 42 (30-50) months six patients were lost of follow-up, 13 patients died and 16 patients reached the combined renal end-point. Stratification according to the mean of aPWV (10  m/s), Kaplan-Meier analysis revealed increased mortality with aPWV ≥10  m/s (log-rank P < 0.05). Stepwise logistic regression analysis confirmed aPWV as an independent predictor for mortality in CKD stage 2-4. The hazard ratio of mortality in the cohort with an aPWV at least 10  m/s was 5.1 (1.1-22.9). By contrast, Kaplan-Meier analysis revealed no effect of aPWV on the combined renal end-point (log-rank P = 0.90). DISCUSSION: These results provide the first direct evidence that in patients with CKD stage 2-4, increased aortic stiffness determined by aPWV is a strong independent predictor of all-cause mortality.