Mortality In Hemodialysis Patients Research Articles

MO519: Ferric Citrate Hydrate Improves Levels of Transferrin Saturation in Hemodialysis Patients With Lower Levels of Transferrin Saturation

Abstract BACKGROUND AND AIMS Iron deficiency identified by transferrin saturation (TSAT) is reported as a risk factor for all-cause mortality and cardiovascular events in non-dialysis dependent (NDD) chronic kidney disease (CKD) [1, 2] and for all-cause mortality in hemodialysis patients [3]. Ferric citrate hydrate (FC, Riona®), an oral iron-based phosphate binder in CKD patients, is also approved as an iron preparation for iron-deficiency anemia (IDA) in Japan in 2021. In the USA, ferric citrate (Auryxia®) is approved as a phosphate binder for dialysis-dependent CKD and an iron replacement product for the treatment of IDA in patients with NDD-CKD. FC or ferric citrate increased TSAT in patients with NDD-CKD and IDA [4]. However, a few data show that whether FC or ferric citrate has the similar effect in hemodialysis patients whose TSAT is <20%. Considering the additional indication of IDA in Japan, we investigated the FC's effect on TSAT by using the data obtained from the ASTRIO study [5], which was conducted in Japanese hemodialysis (HD) patients. METHOD We conducted a retrospective study using the data of ASTRIO study [5], which is a randomized, prospective, open-label, multicenter 24-week study to investigate the FC's effect on anemia management compared with non-iron-based phosphate binders (PBs) in Japanese HD patients with hyperphosphatemia. Ninety-three patients taking non-iron-based PBs were randomized 1:1 to continue PBs (control) or switch to FC. During 24-week study, serum phosphate and hemoglobin were controlled, 3.5–6.0 mg/dL and 10–12 g/dL, respectively. From 93 patients (FC, n = 48; control, n = 45), we extracted 41 patients (FC, n = 21; control, n = 20) whose TSAT at baseline was <20% and compared the levels of TSAT and other iron related parameters between FC group and control group. RESULTS In the ASTRIO study, the mean (SD) levels of TSAT (%) was 14.3 (4.0) at baseline and rapidly increased to 25.0 (11.1) at 4 weeks in the FC group. After that, the levels of TSAT were almost unchanged in the FC group, whereas, in the control group, the mean (SD) levels of TSAT were almost unchanged during the 24-week study. The mean (SD) levels of serum ferritin gradually increased until week 12 and subsequently showed to be stabilized in the FC group, whereas, in the control group, these were almost unchanged during the 24-week study (Table 1). CONCLUSION In Japanese HD patients whose TSAT was <20%, FC rapidly increased TSAT compared with control. We will also investigate the FC's effect on TSAT in HD patients from the post-marketing surveillance study, the prospective, multicenter and observational, up to maximum 2 years treatment.

MO930: Does Oral Sodium Bicarbonate Improve Protein Metabolism and Regeneration in Esrd Patients on Maintenance Hemodialysis?

Abstract BACKGROUND AND AIMS Uremic metabolic acidosis with decreased bicarbonate levels is frequent in hemodialysis patients, and its correction is one of the goals to achieve adequate dialysis. Unfortunately, the bicarbonate delivered through the dialysate may be inadequate to correct the whole acid load. Most hemodialysis data show that about 50% of patients fail to meet a bicarbonate level within the normal range before each dialysis session. Furthermore, low predialysis bicarbonate levels of <22 mmols/L have been linked with increased malnutrition, inflammation and all-cause mortality in hemodialysis patients. This study investigates whether oral sodium bicarbonate supplementation in acidotic hemodialysis patients will improve normalized protein catabolic rate (nPCR) and serum albumin as indicators of nutritional adequacy. METHOD An interventional study was conducted in a trusted hemodialysis unit in Baghdad, Iraq, from 1 September to 1 December 2021. A total of 50 adult prevalent hemodialysis patients were recruited. Out of 50 patients, 26 patients received oral sodium bicarbonate 500 mg/day, and 24 were matched controls. All patients had no significant residual renal function with thrice/week dialysis through arteriovenous fistulae. Serum albumin and the normalized protein catabolism ratio were measured at baseline and 3 months. In addition, anthropometric measures and essential lab data were recorded, including pre-HD arterial pH, serum bicarbonate, serum creatinine, serum Na, k, body weight, interdialytic weight gain, predialysis systolic and diastolic blood pressure and spKt/V. RESULTS The mean age of the study group was 48.76 + 16.21 years with 27 females. The median dialysis duration was (3 years). We found no statistically significant difference in the nPCR and serum albumin between the two groups at 3 months. There was a significant difference in the serum bicarbonate level in the intervention group with a P-value of 0.00. In addition, there were significant differences in arterial PH (P-value 0.008) and serum potassium (P-value 0.039) at 3 months. Serum potassium decreased in the intervention group to the range of (3.9–5.8 meq/L) in comparison to (4.2–6.7 meq/L) in the control group. There was no statistically significant interdialytic weight gain or change in systolic blood pressure at 3 months between the two groups (P-values 0.4 and 0.07), respectively. CONCLUSION Optimal dialysis dose and acidosis correction are not enough to achieve adequate protein metabolism, indicating poor protein intake by Iraqi HD patients, which mandates proper nutritional counseling.

MO858: Early Morning Haemodynamic Changes and Left Ventricular Hypertrophy and Mortality In Haemodialysis Patients

Abstract BACKGROUND AND AIMS Amplified early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk in the general population. The early morning changes in these parameters have not been investigated in the haemodialysis population. METHOD In a pilot, single centre, study including a series of 58 haemodialysis patients we measured the pre-awakening BP and HR surges and the nocturnal dipping of the same parameters as well as other established indicators of autonomic function (weighted 24h systolic BP and HR variability) and tested their relationship with the left ventricular mass index (LVMI) and with the risk of death over a median follow up of 40 months. RESULTS The pre-awakening HR surge (r = –0.46; P = 0.001) was inversely associated with LVMI and the risk of death [HR (1 unit): 0.89, 95% confidence interval: 0.83–0.96; P = 0.001] while the corresponding BP surge largely failed to associate with these outcomes. The link between the pre-awakening HR surge with LVMI and death was robust and largely independent of established risk factors in the haemodialysis population, including the nocturnal dipping of BP. Weighted 24 h systolic BP and HR variability did not correlate with LVMI (all P > 0.11) nor with the risk of death (P > 0.11) and these parameters were also independent of the nocturnal dipping of systolic BP and HR. CONCLUSION This pilot study suggests that the low early morning changes in HR, likely reflecting enhanced sympathetic activity, entail a high risk for LVH and mortality in the haemodialysis population.

MO905: Calcification of Branches is Superior to Abdominal Aortic Calcification in Predicting Mortality of Hemodialysis Patients

Abstract BACKGROUND AND AIMS Vascular calcification (VC) is considered to be an important initiating risk factor of cardiovascular events, which contributes to the leading cause of death in maintenance hemodialysis (MHD) patients. VC has a high incidence and has been reported to predict the mortality of MHD patients. Inspired by an extreme example of VC in dialysis patients, calciphylaxis (which involves extensive calcification of small- and medium- arteries with poor prognosis), we hypothesized that VC of branches was a better predictor of mortality than abdominal aortic calcification. Therefore, a cohort study based on MHD patients was constructed to investigate the distribution characteristics of VC, compare the predictive value of VC on mortality among different arteries, and explore a comprehensive model predicting mortality. METHOD A total of 1583 patients in our Blood Purification Center from January 2015 to September 2017 were screened, and 237 eligible patients were finally included. Abdominal-pelvic computed tomography images were collected and an open-source software 3D Slicer (version 4.11) was used to calculate the calcification volume in abdominal aorta, celiac trunk, superior and inferior mesenteric artery, renal artery, common iliac artery and internal iliac artery. Demographic and clinical data including medical history and some laboratory indexes were collected. Patients were followed-up until all-cause death or September 2020. Cause of death and survival time were recorded in detail. The area under the curve (AUC) of Time-dependent receiver operating curves (ROC) was calculated to evaluate the predictive value of arterial calcification. 80% of cases were randomly assigned to the training dataset and the remaining were assigned to the validation dataset. Lasso regression was performed to screen variables. Cox proportional hazards regression was performed to construct the predicting model and nomogram. C-index, calibration and decision curve analysis were used to evaluate the comprehensive model. SPSS software (version 26.0) and R software (version 4.1.2) perform statistical analysis. RESULTS The prevalence of total VC is 95.36%. Among the abdominal arteries, abdominal aortic calcification is the most prevalent (88.61%), followed by calcification of internal iliac artery (85.65%) and common iliac artery (80.17%). Median survival time was 37.00 (1.00–70.00) months. The 1-year survival rate, 3-year survival rate and 5-year survival rate were 73.42%, 50.01% and 35.43%, respectively. Cardiovascular disease accounts for 54.01% of the death cause. AUC of Time-dependent ROC by internal iliac artery and mesenteric artery calcification for predicting mortality is significantly higher than that of other arterial calcification. Internal iliac artery calcification (IIAC) was screened out as the most representative predictor for all-cause death among the calcification of arterial calcification by lasso regression. When analyzing IIAC and other clinical data, age (hazard ratio 1.03, P < 0.001), serum albumin level (hazard ratio 0.919, P < 0.001) and IIAC (hazard ratio 1.36, P = 0.003) were independent factor of mortality in HD patients. The nomogram based on Cox proportional hazards model is shown in Figure 1. C-index of the model was 74.09%. Decision curves of Cox proportional hazards model from training dataset and validation dataset showed the reliable predictive value of Cox model (Figure 2). CONCLUSION This is the first study evaluating the calcification volume of abdominal aortic branches and comparing their predictive values. In conclusion, calcification of abdominal aortic branches, especially internal iliac artery, is a better predictor for mortality of HD patients than abdominal aortic calcification. Our concern with calcification of large arteries in MHD patients needs to be shifted to smaller branch arteries.

Severe Anemia and Six-Month All-Cause Mortality in Chronic Kidney Disease Patients Undergoing Hemodialysis

Anemia is often found in patients with Chronic Kidney Diseases (CKD). Anemia can affect poor outcomes in hemodialysis patients. However, no publications examined the role of severe anemia as a predictor factor in six-month all-cause mortality in hemodialysis patients. Therefore, further study was needed to answer these questions. This study aimed to determine the role of severe anemia and six-month all-cause mortality in hemodialysis patients. The cohort design study was carried out from October 2019 to March 2020 at the Hemodialysis Unit of Roemani Muhammadiyah Hospital Semarang. The dependent variable was severe anemia, defined as hemoglobin levels <8.0 g/dL. The mortality rate was investigated over six months after the baseline measurements. Among 85 respondents, 35 (41.2%) respondents were categorized into severe anemia, and 50 (58.8%) respondents were categorized into non-severe anemia groups. The respondents consisted of 54 (63.5%) males and 31 (36.5%) females. The hemoglobin level in the severe and non-severe anemia groups was 7.2 ± 0.6 and 9.5 ± 1.2 (mean ± standard deviation). The Kaplan Meier survival curve showed that the non-severe anemia group had a higher survival rate than the severe anemia group (98.0% vs. 82.9%, p = 0.011). The Cox regression analysis found a significant relationship between anemia severity and 6-month all-cause mortality in hemodialysis patients (p = 0.027; Hazard ratio: 9.3). Severe anemia plays a role as a predictor factor in six-month all-cause mortality among hemodialysis patients.

The impact of quality of life measured by WHOQOL-BREF on mortality in maintenance hemodialysis patients: a single center retrospective cross-sectional study.

Several previous studies have reported that quality of life (QoL) in hemodialysis patients affects mortality. However, the 36-item Short Form Health Survey, which has been used mainly in previous studies, is complicated in terms of questionnaire composition and interpretation. This study aimed to identify the impact of QoL on mortality in hemodialysis patients using an easier and simpler diagnostic tool. This retrospective study included 160 hemodialysis patients. QoL was evaluated using the World Health Organization Quality of Life Questionnaire-Brief version (WHOQOL-BREF). Psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, and Pittsburgh Sleep Quality Index. We also evaluated medical factors, such as dialysis adequacy and laboratory results. The mean hemodialysis vintage was 70.7±38.0 months. The proportion of patients who were elderly was higher in the mortality group than in the surviving group, and the Charlson Comorbidity Index score was also higher in the former group. Of the four domains of the WHOQOL-BREF, the physical health and psychological scores of the mortality group were significantly lower than those of the survival group. When the score in the physical health domain or psychological domain was ≤10, the 10-year mortality rate after hemodialysis initiation increased by approximately 2.3- and 2-fold, respectively. QoL may have a significant effect on mortality in patients undergoing hemodialysis. The WHOQOL-BREF is an instrument that can measure QoL relatively easily and can be used to improve the long-term prognosis of patients undergoing hemodialysis.

An optimized machine learning framework for predicting intradialytic hypotension using indexes of chronic kidney disease-mineral and bone disorders

Intradialytic hypotension (IDH) is the most common acute complication in hemodialysis (HD) sessions and is associated with increased morbidity and mortality in HD patients. To prevent the episode of IDH, it is critical to predict its occurrence. Chronic kidney disease-mineral and bone disorders (CKD-MBD) induce cardiac and vascular calcification, which impairs the compensatory mechanisms of blood pressure during HD. In this study, we proposed a feature selection framework called BSWEGWO_KELM to analyze 1940 records from 178 HD patients, which was based on an enhanced grey wolf optimization (GWO) algorithm and the kernel extreme learning machine (KELM). Then, global optimization experiments, together with feature selection experiments on public data sets and HD dataset, were performed to verify the effectiveness of the BSWEGWO_KELM method. The experimental results showed that the established BSWEGWO_KELM had the capability of screening out the key indicators such as dialysis vintage, mean arterial pressure (MAP), alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH). Consequently, BSWEGWO_KELM can be applied as a practical and accurate method to predict IDH.

Role of Fracture Risk Assessment Tool and Bone Turnover Markers in Predicting All-Cause and Cardiovascular Mortality in Hemodialysis Patients.

BackgroundFracture Risk Assessment Tool (FRAX) and bone turnover markers (BTMs) predict fractures in the general population. However, the role of FRAX and BTMs in predicting mortality remains uncertain in hemodialysis (HD) patients.MethodsOne hundred and sixty-four HD patients stratified by low or high risk of 10-year fracture probability using FRAX. High risk of fracture was defined as 10-year probability of hip fracture ≥3% or major osteoporotic fracture ≥20%. The association of high risk of fracture and BTMs with all-cause mortality and cardiovascular (CV) mortality were evaluated using multivariate-adjusted Cox regression analysis.ResultsEighty-five (51.8%) patients were classified as high risk of fracture based on FRAX among 164 HD patients. During a mean follow-up period of 3.5 ± 1.0 years, there were 39 all-cause deaths and 23 CV deaths. In multivariate-adjusted Cox regression, high risk of fracture based on FRAX was independently associated with all-cause mortality [hazard ratio (HR): 2.493, 95% confidence interval (CI): 1.026–6.056, p = 0.044) but not with CV mortality (HR: 2.129, 95% CI: 0.677–6.700, p = 0.196). There were no associations between BTMs and mortality risk. Furthermore, lower geriatric nutritional risk index (GNRI) was significantly associated with increased CV mortality (HR: 0.888, 95% CI: 0.802–0.983, p = 0.022) after adjusting by confounding variables.ConclusionHigh risk of fracture using FRAX was an independent predictor of all-cause mortality in patients undergoing HD. FRAX, rather than BTMs, has an important role of prognostic significance in HD patients.

β-Blocker Use and Cardiovascular Outcomes in Hemodialysis: A Systematic Review

Rationale & ObjectiveThere is conflicting evidence regarding the type of β-blockers to use in dialysis patients. This systematic review seeks to determine whether highly dialyzable β-blockers are associated with higher rates of cardiovascular events and mortality in hemodialysis patients than poorly dialyzable β-blockers.Study DesignA systematic review of the existing literature was conducted. A meta-analysis was performed using data from the selected studies.Setting & Study PopulationsParticipants were from the United States, Canada, and Taiwan. The mean ages of participants ranged from 55.9-75.7 years.Selection Criteria for StudiesWe searched the Ovid MEDLINE database from 1990 to September 2020. Studies without adult hemodialysis participants and without comparisons of at least 2 β-blockers of different dialyzability were excluded.Data ExtractionBaseline and adjusted outcome data were extracted from each study.Analytical ApproachRandom-effects models were used to calculate pooled risk ratios using fully adjusted models from individual studies.ResultsFour cohort studies were included. Pooling fully adjusted models, highly dialyzable β-blockers did not influence mortality (HR, 0.94; 95% CI, 0.81-1.08; I2 = 0.84) compared with poorly dialyzable β-blockers but were associated with a reduction in cardiovascular events (HR, 0.88; 95% CI, 0.83-0.93). There was significant heterogeneity between studies (I2 = 0.35). Only 1 study reported on adverse events. Intradialytic hypotension was more common in those on carvedilol (a poorly dialyzable β-blocker) compared with those on metoprolol (a highly dialyzable β-blocker; adjusted incidence rate ratio, 1.10; 95% CI, 1.09-1.11).LimitationsNo randomized controlled trials were identified. Each study used different analytic methods and different definitions for outcomes. Classifications of β-blockers varied. Only 1 study reported on adverse events.ConclusionsPooled data suggest highly dialyzable β-blockers are associated with similar mortality events and fewer cardiovascular events compared with poorly dialyzable β-blockers.

Serodetection of Cytomegalovirus and Epstein - Barr virus Antibodies Among Hemodialysis Patients

The infection with herpesviruses as Human herpes virus-5 (cytomegalovirus-CMV) and Human herpes virus-4 (Epstein – Barr virus -EBV) is one of the main causes of morbidity and mortality in hemodialysis patients. This study aims to investigate the serostatus of CMV and EBV in patients with renal failure who underwent hemodialysis. The study included 134 cases (55 females and 79 males) with an age range of 35-68 years (mean age 37.43±13.42 years). HCMV-IgG, IgM and EBV-IgG, EBV-IgM were determined in subjects' sera. 87 of 134 (65%) were underwent hemodialysis, while 47 (35%) had normal kidney functions without HCV infection. 68 (78.2%) and 31 (35.6%) cases out 87 hemodialysis patients were positive for CMV-IgG and IgM antibodies, respectively. On the other hand, 56.3% and 20.7% of the 87 hemodialysis patients were positive for EBV-IgG and IgM antibodies, respectively. There is no significant differences were observed between females and males in terms of seroprevelance rates. The rate of positive CMV-IgG among 48-64 years hemodialysis patients was high, Whereas, EBV-IgG were detected among 39-67 years. Our data suggest that seroprevalence of CMV and EBV antibodies among hemodialysis cases is a high and cause complications for these patients.

Cognitive Domain Impairment and All-Cause Mortality in Older Patients Undergoing Hemodialysis

The highly prevalent cognitive impairment in hemodialysis patients is associated with all-cause mortality; however, the role of different cognitive domain impairments in this association is still not clarified. Our objective was to determine the association between cognitive domain impairment and all-cause mortality in elderly adult patients undergoing hemodialysis. We conducted a prospective cohort study including patients from 11 hemodialysis centers in Beijing. Baseline data were collected, and a series of neuropsychological batteries covering 5 domains of cognitive function were included for the assessment of cognitive function. According to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-V), the patients were classified as normal, mild, and major cognitive impairment for global and domain cognitive function, then followed up for 1 year. Kaplan–Meier survival analysis was used to compare the difference in the cumulative survival rate in different cognitive domains. A multivariate Cox proportional hazards regression analysis was used to determine the association between global or domain cognitive impairment and all-cause mortality. A total of 613 patients were enrolled, the mean age was 63.82 ± 7.14 years old, and 42.1% were women. After 49.53 ± 8.42 weeks of follow-up, 69 deaths occurred. Kaplan–Meier plots demonstrated a significant association of cognitive impairment in memory, executive function, attention, and language domains with all-cause death. Multivariate Cox regression analysis showed that mild and major impairment of global cognition (HR = 2.89 (95% CI, 1.01–8.34), p = 0.049 and HR = 4.35 (95% CI, 1.55–12.16), p = 0.005, respectively), executive cognitive domain (HR = 2.51 (95% CI, 1.20–5.24), p = 0.014; HR = 3.91 (95% CI, 1.70–9.03), p = 0.001, respectively), and memory cognitive domain (HR = 2.13 (95% CI, 1.07–4.24), p = 0.031; HR = 3.67 (95% CI, 1.71–7.92), p = 0.001, respectively) were associated with all-cause mortality. Combined impairment of 3, 4, and 5 cognitive domains was associated with all-cause mortality [HR = 5.75 (95% CI, 1.88–17.57), p = 0.002; HR = 12.42 (95% CI, 3.69–41.80), p < 0.001; HR = 13.48 (95% CI, 3.38–53.73), p < 0.001, respectively]. We demonstrate an association between the executive and memory cognitive domain impairment and all-cause mortality in hemodialysis patients. Our data suggest that the impairments in these cognitive domains might help in the early identification of hemodialysis patients at risk of death.

Frequency of Hepatitis C Viral Infection in Maintenance Hemodialysis patients

Background: Blood and blood products mainly transmit HCV. In developing countries Hepatitis C virus (HCV) is one of the leading pathogen that cause serious morbidity and mortality in hemodialysis patients. Transfusion of blood and duration of hemodialysis are the most important factors in transmission of HCV. We aimed to evaluate the frequency of hepatitis C infection in maintenance hemodialysis patients&#x0D; Material and method: It was a cross sectional study conducted at Mayo hospital, Lahore. Patients who met inclusion/exclusion criteria were electively admitted from emergency department. Informed consent from patients about their inclusion in the study and approval from the ethical committee of the hospital was taken. Relevant history and clinical examination was done of patients on maintenance hemodialysis . Venous samples for anti HCV antibodies by ELISA were taken. All samples sent to a ‘Central Laboratory of Mayo Hospital, Lahore’. All the relevant information including anti HCV antibodies by ELIZA and confounding variable like age, gender were noted on a Performa.&#x0D; Results&#x0D; Our study showed that frequency of HCV infection in CKD (chronic kidney disease) patients on maintenance hemodialysis was 25.7 percent.&#x0D; &#x0D; Conclusion:&#x0D; Our study concluded that there is a greater risk of acquiring hepatitis C infection in patients on maintenance hemodialysis. The control of contagion, decrease frequency of blood transfusions and cross-infections are the key factors to reduce occurrence of HCV in patients with hemodialysis.

Early morning hemodynamic changes and left ventricular hypertrophy and mortality in hemodialysis patients.

An exaggeration of the early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk. The early morning changes in these parameters have not been investigated in the hemodialysis population. In a pilot, single center study including a series of 58 patients we measured the pre-awakening BP and HR surges and the nocturnal dipping of the same parameters as well as other established indicators of autonomic function (weighted 24h systolic BP and HR variability) and tested their relationship with the left ventricular mass index (LVMI) and with the risk of death over a median follow up of 40months. The pre-awakening HR surge (r = -0.46, P = 0.001) but not the corresponding BP surge (r = -0.1, P = 0.98) was associated with LVMI and the risk of death [HR (1 unit): 0.89, 95% CI 0.83-0.96, P = 0.001]. The link between the pre-awakening HR surge with these outcome measures was robust and largely independent of established risk factors in the hemodialysis population, including the nocturnal dipping of BP. Weighted 24h systolic BP and HR variability did not correlate with LVMI (all P > 0.11) nor with the risk of death (P > 0.11) and were also independent of the nocturnal dipping of systolic BP and HR. This pilot study suggests that the low early morning changes in HR, likely reflecting enhanced sympathetic activity, entail a high risk for left ventricular hypertrophy (LVH) and mortality in the hemodialysis population.

Serum Pentraxin3: Its Relationship with left Ventricular Mass Index and its role as a Predictor for Cardiovascular Mortality in Hemodialysis Patients

Serum Pentraxin3: Its Relationship with left Ventricular Mass Index and its role as a Predictor for Cardiovascular Mortality in Hemodialysis Patients

Diabetes acts on mortality in hemodialysis patients predicted by asymmetric dimethylarginine and inflammation

BackgroundThe mortality rate of diabetic patients on dialysis is higher than that of non-diabetic patients. Asymmetric dimethylarginine and inflammation are strong predictors of death in hemodialysis. This study aimed to evaluate asymmetric dimethylarginine and C-reactive protein interaction in predicting mortality in hemodialysis according to the presence or absence of diabetes. MethodsAsymmetric dimethylarginine and C-reactive protein were measured in 202 patients in maintenance hemodialysis assembled from 2011 to 2012 and followed for four years. Effect modification of C-reactive protein on the relationship between asymmetric dimethylarginine and all-cause mortality was investigated dividing the population into four categories according to the median of asymmetric dimethylarginine and C-reactive protein. ResultsAsymmetric dimethylarginine and C-reactive protein levels were similar between diabetics and non-diabetics. Asymmetric dimethylarginine – median IQR μM – (1.95 1.75–2.54 versus 1.03 0.81–1.55 P=0.000) differed in non-diabetics with or without evolution to death (HR 2379 CI 1.36–3.68 P=0.000) and was similar in diabetics without or with evolution to death. Among non-diabetics, the category with higher asymmetric dimethylarginine and C-reactive protein levels exhibited the highest mortality (69.0% P=0.000). No differences in mortality were seen in diabetics. A joint effect was found between asymmetric dimethylarginine and C-reactive protein, explaining all-cause mortality (HR 15.21 CI 3.50–66.12 P=0.000). ConclusionsAsymmetric dimethylarginine is an independent predictor of all-cause mortality in non-diabetic patients in hemodialysis. Other risk factors may overlap asymmetric dimethylarginine in people with diabetes. Inflammation dramatically increases the risk of death associated with high plasma asymmetric dimethylarginine in hemodialysis.

Assessing proximate intermediates between ambient temperature, hospital admissions, and mortality in hemodialysis patients.

Typical thermoregulatory responses to elevated temperatures among healthy individuals include reduced blood pressure and perspiration. Individuals with end-stage kidney disease (ESKD) are susceptible to systemic fluctuations caused by ambient temperature changes that may increase morbidity and mortality. We investigated whether pre-dialysis systolic blood pressure (preSBP) and interdialytic weight gain (IDWG) can independently mediate the association between ambient temperature, all-cause hospital admissions (ACHA), and all-cause mortality (ACM). The study population consisted of ESKD patients receiving hemodialysis treatments at Fresenius Medical Care facilities in Philadelphia County, PA, from 2011 to 2019 (n=1981). Within a time-to-event framework, we estimated the association between daily maximum dry-bulb temperature (TMAX) and, as separate models, ACHA and ACM during warmer calendar months. Clinically measured preSBP and IDWG responses to temperature increases were estimated using linear mixed effect models. We employed the difference (c-c') method to decompose total effect models for ACHA and ACM using preSBP and IDWG as time-dependent mediators. Covariate adjustments for exposure-mediator and total and direct effect models include age, race, ethnicity, blood pressure medication use, treatment location, preSBP, and IDWG. We considered lags up to two days for exposure and 1-day lag for mediator variables (Lag 2-Lag 1) to assure temporality between exposure-outcome models. Sensitivity analyses for 2-day (Lag 2-only) and 1-day (Lag 1-only) lag structures were also conducted. Based on Lag 2- Lag 1 temporal ordering, 1°C increase in daily TMAX was associated with increased hazard of ACHA by 1.4% (adjusted hazard ratio (HR), 1.014; 95% confidence interval, 1.007-1.021) and ACM 7.5% (adjusted HR, 1.075, 1.050-1.100). Short-term lag exposures to 1°C increase in temperature predicted mean reductions in IDWG and preSBP by 0.013-0.015% and 0.168-0.229mmHg, respectively. Mediation analysis for ACHA identified significant indirect effects for all three studied pathways (preSBP, IDWG, and preSBP+IDWG) and significant indirect effects for IDWG and conjoined preSBP+IDWG pathways for ACM. Of note, only 1.03% of the association between temperature and ACM was mediated through preSBP. The mechanistic path for IDWG, independent of preSBP, demonstrated inconsistent mediation and, consequently, potential suppression effects in ACHA (-15.5%) and ACM (-6.3%) based on combined pathway models. Proportion mediated estimates from preSBP+IDWG pathways achieved 2.2% and 0.3% in combined pathway analysis for ACHA and ACM outcomes, respectively. Lag 2 discrete-time ACM mediation models exhibited consistent mediation for all three pathways suggesting that 2-day lag in IDWG and preSBP responses can explain 2.11% and 4.41% of total effect association between temperature and mortality, respectively. We corroborated the previously reported association between ambient temperature, ACHA and ACM. Our results foster the understanding of potential physiological linkages that may explain or suppress temperature-driven hospital admissions and mortality risks. Of note, concomitant changes in preSBP and IDWG may have little intermediary effect when analyzed in combined pathway models. These findings advance our assessment of candidate interventions to reduce the impact of outdoor temperature change on ESKD patients.

The Relationship of Epicardial Adipose Tissue and Cardiovascular Disease in Chronic Kidney Disease and Hemodialysis Patients.

Cardiovascular diseases remain the most common cause of morbidity and mortality in chronic kidney disease patients undergoing hemodialysis. Epicardial adipose tissue (EAT), visceral fat depot of the heart, was found to be associated with coronary artery disease in cardiac and non-cardiac patients. Additionally, EAT has been proposed as a novel cardiovascular risk in the general population and in end-stage renal disease patients. It has also been shown that EAT, more than other subcutaneous adipose tissue deposits, acts as a highly active organ producing several bioactive adipokines, and proinflammatory and proatherogenic cytokines. Therefore, increased visceral adiposity is associated with proinflammatory activity, impaired insulin sensitivity, increased risk of atherosclerosis, and high morbidity and mortality in hemodialysis patients. In the present review, we aimed to demonstrate the role of EAT in the pathophysiological mechanisms of increased cardiovascular morbidity and mortality in hemodialysis patients.

Association of cardiac autonomic neuropathy assessed by heart rate response during exercise with intradialytic hypotension and mortality in hemodialysis patients

The heart rate (HR) reflects the dynamic behavior of the autonomic nervous system, and HR profiles during the exercise test provide prognostic information. However, there are no reports of these factors in hemodialysis patients. Data from 256 patients (mean 68.8 years old) who underwent an exercise test were statistically analyzed. Patients were evaluated for the percent HR reserve from HR at peak exercise, HR recovery for one minute after peak exercise, and exercise capacity, as well as intradialytic hypotension (IDH). The prevalence of chronotropic incompetence (96.1%), defined as under 80% HR reserve, and abnormal HR recovery (60.5%), defined as under 12 beats, were very common. Eighty-four deaths occurred during the follow-up period (median, 3.8 years). A slow HR recovery under 7 beats was associated with IDH after adjustment (odds ratio 2.7, 95% confidence interval 1.1-6.4). HR recovery under 12 beats (hazard ratio over study period 5.1, 95% confidence interval 2.5-10.5), HR reserve under 26.2% (3.4, 1.7-6.8), and IDH (1.7, 1.1-2.8) were associated with all-cause mortality after adjustment. Considering the confounding of all three variables, only HR recovery under 12 beats remained associated with the all-cause and cause-specific mortality ("cardiovascular" and "non-cardiovascular"). This association was consistent even in subgroup analyses based on the presence of diabetes and cardiovascular disease. Thus, HR profiles during the exercise can reflect potential health conditions related to cardiac autonomic neuropathy in hemodialysis patients that affect IDH and their survival.

The Role of Physical Activity and Mortality in Hemodialysis Patients: A Review.

Available data indicated that physical activity was related to improved outcomes in hemodialysis patients. Multiple observational studies involving different cohorts have reported that increased physical activity level was associated with decreased mortality among hemodialysis patients. Therefore, promoting physical activity has become an increasingly critical and promising approach to improving cardiovascular health and clinical outcomes in hemodialysis patients. This review summarizes the published articles regarding physical activity and hemodialysis patients, focusing on mortality and strategy to promote physical activity.

Ferric citrate hydrate is associated with a reduced cost of drugs and a smaller change in red blood cell distribution width

The ASTRIO study was a randomised, multicentre, 24-week study that compared the effects of ferric citrate hydrate (FC) and non-iron-based phosphate binders (control) on anaemia management in haemodialysis (HD) patients receiving erythropoiesis-stimulating agents (ESAs). In that study, FC reduced the doses of ESAs and intravenous iron without affecting haemoglobin (Hb); however, the cost-effectiveness of FC was unclear. We retrospectively implemented a cost-effectiveness analysis comparing the incremental cost-effectiveness ratios (ICERs) in FC (n = 42) and control (n = 40) groups in patients with serum phosphate and Hb controlled within the ranges of 3.5–6.0 mg/dL and 10–12 g/dL, respectively. Costs included drug costs of phosphate binders, ESAs, and intravenous iron. Elevated red cell distribution width (RDW) has been reported to be associated with mortality in HD patients and was therefore used as an effectiveness index. The mean (95% confidence interval) differences in drug costs and RDW between the FC and control groups were US$ − 421.36 (− 778.94 to − 63.78, p = 0.02) and − 0.83% (− 1.61 to – 0.05, p = 0.04), respectively. ICER indicated a decrease of US$ 507.66 per 1% decrease in RDW. FC was more cost-effective than non-iron-based phosphate binders. Iron absorbed via FC could promote erythropoiesis and contribute to renal anaemia treatment.