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IntroductionInflammation is highly prevalent among patients with end-stage kidney disease and is associated with adverse outcomes. We aimed to investigate longitudinal changes in inflammatory markers in a diverse international incident hemodialysis patient population.MethodsThe MONitoring Dialysis Outcomes (MONDO) Consortium encompasses hemodialysis databases from 31 countries in Europe, North America, South America, and Asia. The MONDO database was queried for inflammatory markers (total white blood cell count [WBC], neutrophil count, lymphocyte count, serum albumin, and C-reactive protein [CRP]) and hemoglobin levels in incident hemodialysis patients. Laboratory parameters were measured every month. Patients were stratified by survival time (≤6 months, >6 to 12 months, >12 to 18 months, >18 to 24 months, >24 to 30 months, >30 to 36 months, and >36 months) following dialysis initiation. We used cubic B-spline basis function to evaluate temporal changes in inflammatory parameters in relationship with patient survival.ResultsWe studied 18,726 incident hemodialysis patients. Their age at dialysis initiation was 71.3 ± 11.9 years; 10,802 (58%) were males. Within the first 6 months, 2068 (11%) patients died, and 12,295 patients (67%) survived >36 months (survivor cohort). Hemodialysis patients who died showed a distinct biphasic pattern of change in inflammatory markers where an initial decline of inflammation was followed by a rapid rise that was consistently evident approximately 6 months before death. This pattern was similar in all patients who died and was consistent across the survival time intervals. In contrast, in the survivor cohort, we observed initial decline of inflammation followed by sustained low levels of inflammatory biomarkers.ConclusionOur international study of incident hemodialysis patients highlights a temporal relationship between serial measurements of inflammatory markers and patient survival. This finding may inform the development of prognostic models, such as the integration of dynamic changes in inflammatory markers for individual risk profiling and guiding preventive and therapeutic interventions.

IntroductionThe clinical impact of COVID-19 has not been established in the dialysis population. We evaluated the trajectories of clinical and laboratory parameters in hemodialysis (HD) patients.MethodsWe used data from adult HD patients treated at an integrated kidney disease company who received a reverse transcription polymerase chain reaction (RT-PCR) test to investigate suspicion of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection between May 1 and September 1, 2020. Nonparametric smoothing splines were used to fit data for individual trajectories and estimate the mean change over time in patients testing positive or negative for SARS-CoV-2 and those who survived or died within 30 days of first suspicion or positive test date. For each clinical parameter of interest, the difference in average daily changes between COVID-19 positive versus negative group and COVID-19 survivor versus nonsurvivor group was estimated by fitting a linear mixed effects model based on measurements in the 14 days before (i.e., Day -14 to Day 0) Day 0.ResultsThere were 12,836 HD patients with a suspicion of COVID-19 who received RT-PCR testing (8895 SARS-CoV-2 positive). We observed significantly different trends (p

IntroductionThe clinical impact of COVID-19 has not been established in the dialysis population. We evaluated the trajectories of clinical and laboratory parameters in hemodialysis (HD) patients.MethodsWe used data from adult HD patients treated at an integrated kidney disease company who received a reverse transcription polymerase chain reaction (RT-PCR) test to investigate suspicion of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection between May 1 and September 1, 2020. Nonparametric smoothing splines were used to fit data for individual trajectories and estimate the mean change over time in patients testing positive or negative for SARS-CoV-2 and those who survived or died within 30 days of first suspicion or positive test date. For each clinical parameter of interest, the difference in average daily changes between COVID-19 positive versus negative group and COVID-19 survivor versus nonsurvivor group was estimated by fitting a linear mixed effects model based on measurements in the 14 days before (i.e., Day -14 to Day 0) Day 0.ResultsThere were 12,836 HD patients with a suspicion of COVID-19 who received RT-PCR testing (8895 SARS-CoV-2 positive). We observed significantly different trends (p

Background: Cardiac troponin T (cTnT) is key in diagnosing myocardial infarction (MI) but is also elevated in endstage renal disease (ESRD) patients. Specific larger cTnT proteoforms were identified for the acute phase of MI, while in serum of ESRD patients solely small cTnT fragments were found. However, others allocated this to a pre-analytic effect due to abundant thrombin generation in serum. Therefore, we investigated the effect of various anticoagulation methods on cTnT composition and concentration and compared the cTnT composition of MI and ESRD patients. Methods: The agreement of cTnT concentrations between simultaneously collected serum, lithium-heparin (LH) plasma, and ethylenediaminetetraacetic acid (EDTA) plasma was studied using the high-sensitivity (hs-)cTnT immunoassay. cTnT proteoform composition was investigated in a standardized time-dependent manner through spike experiments and in simultaneously collected blood matrixes of MI and ESRD patients. Results: Excellent hs-cTnT concentration agreements were observed across all blood matrixes (slopes > 0.98; 95% CI, 0.96-1.04). Time-dependent degradation (40 kDa intact:29 kDa fragment:15 to 18 kDa fragments) was found in LH plasma and EDTA plasma, and serum in ratios (%) of 90:10:0, 0:5:95, and 0:0:100, respectively (48 h after blood collection). Moreover, gel filtration chromatography (GFC) profiles illustrated mainly larger cTnT proteoforms in MI patients, while in ESRD patients mainly 15 to 18 kDa fragments were found for all matrices. Conclusions: The extent of cTnT degradation in vitro is dependent on the (anti)coagulation method, without impacting hs-cTnT concentrations. Furthermore, mainly larger cTnT proteoforms were present in MI patients, while in ESRD patients mainly small 15 to 18 kDa cTnT fragments were found. These insights are essential when developing a novel hs-cTnT assay targeting larger cTnT proteoforms. [ABSTRACT FROM AUTHOR]

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality.

BackgroundSeasonal mortality differences have been reported in US hemodialysis (HD) patients. Here we examine the effect of seasons on mortality, clinical and laboratory parameters on a global scale.MethodsDatabases from the international Monitoring Dialysis Outcomes (MONDO) consortium were queried to identify patients who received in-center HD for at least 1 year. Clinics were stratified by hemisphere and climate zone (tropical or temperate). We recorded mortality and computed averages of pre-dialysis systolic blood pressure (pre-SBP), interdialytic weight gain (IDWG), serum albumin, and log C-reactive protein (CRP). We explored seasonal effects using cosinor analysis and adjusted linear mixed models globally, and after stratification.ResultsData from 87,399 patients were included (northern temperate: 63,671; northern tropical: 7,159; southern temperate: 13,917; southern tropical: 2,652 patients). Globally, mortality was highest in winter. Following stratification, mortality was significantly lower in spring and summer compared to winter in temperate, but not in tropical zones. Globally, pre-SBP and IDWG were lower in summer and spring as compared to winter, although less pronounced in tropical zones. Except for southern temperate zone, serum albumin levels were higher in winter. CRP levels were highest in winter.ConclusionSignificant global seasonal variations in mortality, pre-SBP, IDWG, albumin and CRP were observed. Seasonal variations in mortality were most pronounced in temperate climate zones.

Reimbursement for chronic dialysis consumes a substantial portion of healthcare costs for a relatively small proportion of the total population. Each country has a unique reimbursement system that attempts to control rising costs. Thus, comparing the reimbursement systems between countries might be helpful to find solutions to minimize costs to society without jeopardizing quality of treatment and outcomes. We conducted a survey of seven countries to compare crude reimbursement for various dialysis modalities and evaluated additional factors, such as inclusion of drugs or physician payments in the reimbursement package, adjustment in rates for specific patient subgroups, and pay for performance therapeutic thresholds. The comparison examines the United States, the province of Ontario in Canada, and five European countries (Belgium, France, Germany, The Netherlands, and the United Kingdom). Important differences between countries exist, resulting in as much as a 3.3-fold difference between highest and lowest reimbursement rates for chronic hemodialysis. Differences persist even when our data were adjusted for per capita gross domestic product. Reimbursement for peritoneal dialysis is lower in most countries except Germany and the United States. The United Kingdom is the only country that has implemented an incentive if patients use an arteriovenous fistula. Although home hemodialysis (prolonged or daily dialysis) allows greater flexibility and better patient outcomes, reimbursement is only incentivized in The Netherlands. Unfortunately, it is not yet clear that such differences save money or improve quality of care. Future research should focus on directly testing both outcomes.

Introduction: In maintenance hemodialysis (HD) patients, low central venous oxygen saturation (ScvO2) and small decline in relative blood volume (RBV) have been associated with adverse outcomes. Here we explore the joint association between ScvO2 and RBV change in relation to all‐cause mortality. Methods: We conducted a retrospective study in maintenance HD patients with central venous catheters as vascular access. During a 6‐month baseline period, Crit‐Line (Fresenius Medical Care, Waltham, MA) was used to measure continuously intradialytic ScvO2 and hematocrit‐based RBV. We defined four groups per median change of RBV and median ScvO2. Patients with ScvO2 above median and RBV change below median were defined as reference. Follow‐up period was 3 years. We constructed Cox proportional hazards model with adjustment for age, diabetes, and dialysis vintage to assess the association between ScvO2 and RBV and all‐cause mortality during follow‐up. Findings: Baseline comprised 5231 dialysis sessions in 216 patients. The median RBV change was −5.5% and median ScvO2 was 58.8%. During follow‐up, 44 patients (20.4%) died. In the adjusted model, all‐cause mortality was highest in patients with ScvO2 below median and RBV change above median (HR 6.32; 95% confidence interval [CI] 1.37–29.06), followed by patients with ScvO2 below median and RBV change below median (HR 5.04; 95% CI 1.14–22.35), and ScvO2 above median and RBV change above median (HR 4.52; 95% CI 0.95–21.36). Discussion: Concurrent combined monitoring of intradialytic ScvO2 and RBV change may provide additional insights into a patient's circulatory status. Patients with low ScvO2 and small changes in RBV may represent a specifically vulnerable group of patients at particularly high risk for adverse outcomes, possibly related to poor cardiac reserve and fluid overload. [ABSTRACT FROM AUTHOR]