Chronic Fluid Overload and Mortality in ESRD Zoccali, Carmine; Moissl, Ulrich; Chazot, Charles ...
Journal of the American Society of Nephrology,
08/2017, Letnik:
28, Številka:
8
Journal Article
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Sustained fluid overload (FO) is considered a major cause of hypertension, heart failure, and mortality in patients with ESRD on maintenance hemodialysis. However, there has not been a cohort study ...investigating the relationship between chronic exposure to FO and mortality in this population. We studied the relationship of baseline and cumulative FO exposure over 1 year with mortality in 39,566 patients with incident ESRD in a large dialysis network in 26 countries using whole-body bioimpedance spectroscopy to assess fluid status. Analyses were applied across three discrete systolic BP (syst-BP) categories (<130, 130-160, and >160 mmHg), with nonoverhydrated patients with syst-BP=130-160 mmHg as the reference category; >200,000 FO measurements were performed over follow-up. Baseline FO value predicted excess risk of mortality across syst-BP categories (<130 mmHg: hazard ratio HR, 1.51; 95% confidence interval 95% CI, 1.38 to 1.65; 130-160 mmHg: HR, 1.25; 95% CI, 1.16 to 1.36; >160 mmHg: HR, 1.30; 95% CI, 1.19 to 1.42; all
<0.001). However, cumulative 1-year FO exposure predicted a higher death risk (
<0.001) across all syst-BP categories (<130 mmHg: HR, 1.94; 95% CI, 1.68 to 2.23; 130-160 mmHg: HR, 1.51; 95% CI, 1.35 to 1.69; >160 mmHg: HR, 1.62; 95% CI, 1.39 to 1.90). In conclusion, chronic exposure to FO in ESRD is a strong risk factor for death across discrete BP categories. Whether treatment policies that account for fluid status monitoring are preferable to policies that account solely for predialysis BP measurements remains to be tested in a clinical trial.
The aim of the paper is to reflect on the current status of bioimpedance spectroscopy (BIS) in fluid management in dialysis patients. BIS identifies fluid overload (FO) as a virtual (overhydration) ...compartment, which is calculated from the difference between the measured extracellular volume and the predicted values based on a fixed hydration of lean and adipose tissue mass. FO is highly prevalent in both hemodialysis (HD) and peritoneal dialysis (PD) patients, while levels of FO are at a population level comparable between PD patients and HD patients when measured before the dialysis treatment. Even mild levels of FO are independently related to outcome in patients on HD, PD as well as in nondialysis patients with advanced chronic kidney disease. FO is not only related to left ventricular hypertrophy (LVH) but also forms part of a multidimensional spectrum with noncardiovascular risk factors such as malnutrition and inflammation. Even after multiple adjustments, FO remains an independent predictor of mortality. BIS-assisted adjustment of dry weight in HD patients has been shown to improve hypertension control and LVH and has resulted in a decline in intradialytic symptomatology. On the other hand, with increased fluid removal, target weight may not always be reached due to an increase in intradialytic symptomatology, and care should be applied in target weight adjustment in fluid overloaded patients with severe malnutrition and/or inflammation. Although a reduction in hospitalization rate was suggested, the effect of BIS-guided dry weight adjustment on mortality has not yet been shown, however, although available studies are underpowered. In PD patients, results have been more equivocal, which may be partly related to differences in treatment protocols or study populations. Future large-scale studies are needed to assess the full potential of BIS.
Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with chronic kidney disease. The issue of ESA safety has been raised in multiple studies, with correlates derived ...for elevated cancer incidence and mortality. Whether these associations are related to ESA dose or the typology of the patient remains obscure.
A multicentre, observational retrospective propensity score-matched study was designed to analyse the effects of weekly ESA dose in 1679 incident haemodialysis (HD) patients. ESA administration was according to standard medical practice. Patients were grouped as quintiles, according to ESA dose, in order to compare mortality and hospitalization data. Using propensity score matching (PSM), we defined two groups of 324 patients receiving weekly threshold ESA doses of either > or ≤8000 IU.
Kaplan-Meier survival curves indicated significant increases in the risk of mortality in patients administered with high doses of ESAs (>8127.4 IU/week). Multivariate Cox models identified a high ESA dose as an independent predictor for all-cause and cardiovascular (CV) mortality. Moreover, logistic regression models identified high ESA doses as an independent predictor for all-cause, CV and infectious hospitalization. PSM analyses confirmed that weekly ESA doses of >8000 IU constitute an independent predictor of all-cause mortality and hospitalization, even though the adjusted cohort displayed the same demographic features, inflammatory profile, clinical HD parameters and haemoglobin levels.
Our data suggest that ESA doses of >8000 IU/week are associated with an increased risk of all-cause mortality and hospitalization in HD patients.
Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index ...(ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period. Groups were matched by propensity score at baseline (6 months after dialysis initiation). The follow-up period (mean of 1.31 years) was stratified into 1 month intervals with delta analyses performed for key ERI-related parameters. Dialysis modality, time interval, and polycystic kidney disease were included in a linear mixed model with the outcome ERI. Baseline ERI was nonsignificantly higher in HDF versus HD treatment. ERI decreased significantly faster in HDF-treated patients than in HD-treated patients, was decreased in both HD and HDF when patients were treated with intravenous darbepoetin alfa, but only in HDF when treated with intravenous recombinant human erythropoietin (rHuEPO). A clear difference between HD- and HDF-treated patients could only be found for patients with high baseline ERI and assigned to intravenous rHuEPO treatment. A significant advantage in terms of lower ERI for patients treated by HDF was found. Sensitivity analysis limited this advantage for HDF to those patients treated with intravenous rHuEPO (not darbepoetin alfa or subcutaneous rHuEPO) and to patients with a high baseline ERI. Thus, our results allow more accurate planning for future clinical trials addressing anemia management in dialysis patients.
Vascular access surveillance of dialysis patients is a challenging task for clinicians. We derived and validated an arteriovenous fistula failure model (AVF-FM) based on machine learning.
The AVF-FM ...is an XG-Boost algorithm aimed at predicting AVF failure within three months among in-centre dialysis patients. The model was trained in the derivation set (70% of initial cohort) by exploiting the information routinely collected in the Nephrocare European Clinical Database (EuCliD
). Model performance was tested by concordance statistic and calibration charts in the remaining 30% of records. Features importance was computed using the SHAP method.
We included 13,369 patients, overall. The Area Under the ROC Curve (AUC-ROC) of AVF-FM was 0.80 (95% CI 0.79-0.81). Model calibration showed excellent representation of observed failure risk. Variables associated with the greatest impact on risk estimates were previous history of AVF complications, followed by access recirculation and other functional parameters including metrics describing temporal pattern of dialysis dose, blood flow, dynamic venous and arterial pressures.
The AVF-FM achieved good discrimination and calibration properties by combining routinely collected clinical and sensor data that require no additional effort by healthcare staff. Therefore, it can potentially enable risk-based personalization of AVF surveillance strategies.
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.
Anemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been ...associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF).
We included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study. All patients were dialyzed three times per week and had fistula/graft as vascular access. Patients were matched at baseline and followed over a one-year period. The courses of hemoglobin levels (Hb) and monthly ESA consumption were compared between the two groups with linear mixed models.
Mean baseline Hb was 11.9±1.3 and 11.8±1.1g/dl in patients on Mixed- and Post-HDF, respectively. While Hb remained stable in patients on Mixed-HDF, it decreased slightly in patients on Post-HDF (at month 12: 11.8±1.2 vs 11.1±1.2g/dl). This tendency was confirmed by our linear mixed model (p = 0.0514 for treatment x time interaction). Baseline median ESA consumption was 6000 Q1:0;Q3:16000 IU/4 weeks in both groups. Throughout the observation period ESA doses tended to be lower in the Mixed-HDF group (4000 Q1:0;Q3:16000 vs 8000 Q1:0;Q3:20000 IU/4 weeks at month 12; p = 0.0791 for treatment x time interaction). Sensitivity analyses, adjusting for differences not covered by matching at baseline, strengthened our results (Hb: p = 0.0124; ESA: p = 0.0687).
Results of our explorative study suggest that patients on Mixed-HDF may have clinical benefits in terms of anemia management. This may also have a beneficial economic impact. Future studies are needed to confirm our hypothesis-generating results and to provide additional evidence on the potential beneficial effects of Mixed-HDF.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis ...patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.e. at 3 months) to the ESA/iron therapy would be of fundamental importance for planning a successful treatment strategy. To this end, we developed a predictive model designed to support decision-making regarding anemia management in hemodialysis (HD) patients treated in center. An Artificial Neural Network (ANN) algorithm for predicting hemoglobin concentrations three months into the future was developed and evaluated in a retrospective study on a sample population of 1558 HD patients treated with intravenous (IV) darbepoetin alfa, and IV iron (sucrose or gluconate). Model inputs were the last 90 days of patients' medical history and the subsequent 90 days of darbepoetin/iron prescription. Our model was able to predict individual variation of hemoglobin concentration 3 months in the future with a Mean Absolute Error (MAE) of 0.75 g/dL. Error analysis showed a narrow Gaussian distribution centered in 0 g/dL; a root cause analysis identified intercurrent and/or unpredictable events associated with hospitalization, blood transfusion, and laboratory error or misreported hemoglobin values as the main reasons for large discrepancy between predicted versus observed hemoglobin values. Our ANN predictive model offers a simple and reliable tool applicable in daily clinical practice for predicting the long-term response to ESA/iron therapy of HD patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The majority of studies suggesting that online hemodiafiltration reduces the risk of mortality compared to hemodialysis (HD) have been performed in dialysis-prevalent populations. In this report, we ...conducted an epidemiologic study of mortality in incident dialysis patients, comparing post-dilution online hemodiafiltration and high-flux HD, with propensity score matching (PSM) used to correct indication bias.
Our study cohort comprised 3,075 incident dialysis patients treated in 64 Spanish Fresenius Medical Care clinics between January 2009 and December 2012. The primary outcome of this study was to investigate the impact of the type of renal replacement on all-cause mortality. An analysis of cardiovascular mortality was defined as the secondary outcome. To achieve these objectives, patients were followed until December 2016. Patients were categorized as high-flux HD patients if they underwent this treatment exclusively. If >90% of their treatment was with online hemodiafiltration, then the patient was grouped to that modality.
After PSM, a total of 1,012 patients were matched. Compared with patients on high-flux HD, those on online hemodiafiltration received a median replacement volume of 23.45 (interquartile range 21.27-25.51) L/session and manifested 24 and 33% reductions in all-cause and cardiovascular mortality (all-cause mortality hazards ratio HR 0.76, 95% CI 0.62-0.94 p = 0.01; and cardiovascular mortality HR 0.67, 95% CI 0.50-0.90 p = 0.008).
This study shows that post-dilution online hemodiafiltration reduces all-cause and cardiovascular mortality compared to high-flux HD in an incident HD population.
Vascular calcification is a major contributor to the high cardiac burden among hemodialysis patients. A novel in vitro T50-test, which determines calcification propensity of human serum, may identify ...patients at high risk for cardiovascular (CV) disease and mortality. We evaluated whether T50 predicts mortality and hospitalizations among an unselected cohort of hemodialysis patients.
This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 dialysis centers in Spain. T50 and fetuin-A were determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database. After their baseline T50 measurement, patients were followed for two years for the occurrence of all-cause mortality, CV-related mortality, all-cause and CV-related hospitalizations. Outcome assessment was performed with proportional subdistribution hazards regression modelling.
Patients who died during follow-up had a significantly lower T50 at baseline as compared to those who survived (269.6 vs. 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI 0.9933;0.9981). T50 remained significant after inclusion of known predictors. There was no evidence for prediction of CV-related outcomes, but for all-cause hospitalizations (mean c statistic: 0.5284).
T50 was identified as an independent predictor of all-cause mortality among an unselected cohort of hemodialysis patients. However, the additional predictive value of T50 added to known mortality predictors was limited. Future studies are needed to assess the predictive value of T50 for CV-related events in unselected hemodialysis patients.
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