Stable Hemodialysis Patients Research Articles

Circulating microRNAs and vascular calcification in hemodialysis patients.

ObjectiveVascular calcification is common in chronic dialysis patients and is associated with increased morbidity and mortality. However, the role of circulating microRNAs (miRs) in vascular calcification has rarely been investigated. We aimed to determine circulating levels of miRs in hemodialysis patients, and analyzed their relationship with vascular calcification.MethodsSixty-one stable hemodialysis patients were enrolled, including 31 with vascular calcification and 30 without. Demographic and biochemical data were collected and reviewed. The presence and severity of vascular calcification were determined by lumber spine X-ray. Blood levels of miR29a/b, miR223, miR9, and miR21 were determined.ResultsPatients with vascular calcification were older (65.6 ± 9.0 vs. 59.1 ± 7.1 years) with a higher proportion of vascular disease (55% vs. 23%) than those without vascular calcification. Additionally, high-sensitivity C-reactive protein (3.90 vs 2.09 mg/dL) and fibroblast growth factor 23 (17311 vs. 6306 pg/mL) were significantly higher. Patients with vascular calcification also had higher levels of miR29a/b and miR223. Regression analysis indicated that age and miR29a were significant associates of the calcification score.ConclusionsHemodialysis patients with vascular calcification had higher levels of miR 29a/b and miR223 than those without vascular calcification, and circulating miR29a was associated with calcification severity.

The new marker YKL-40, a molecule related to inflammation, is associated with cardiovascular events in stable haemodialysis patients.

BackgroundYKL-40 is a glycoprotein associated with inflammatory conditions, including atherosclerosis and endothelial dysfunction. The objective was to analyse serum YKL-40 levels in a haemodialysis population and explore their association with dialysis dosing measures, inflammation, body composition and development of cardiovascular (CV) events. MethodsWe performed a prospective study of 78 chronic haemodialysis patients enrolled in 2013 and followed up until 2018. At baseline, serum YKL-40, inflammatory and nutrition markers and body composition were assessed. During a median follow-up of 43 (interquartile range 24–66) months, CV events were recorded.ResultsThe mean age of patients was 62 ± 16 years and 66% were men. The mean YKL-40 was 207 ± 106 ng/dL. Higher YKL-40 levels were associated with lower Kt/Vurea, convective volume, serum albumin and prealbumin and with higher troponin T. During follow-up, 50% developed CV events. Cox analysis showed an association between CV events and YKL-40, diabetes, hypertension, C-reactive protein, lower prealbumin, β2-microglobulin, glycosylated haemoglobin and troponin T values. The multivariate Cox analysis confirmed an independent association between CV events and YKL-40 {hazard ratio [HR] 1.067 [95% confidence interval (CI) 1.009–1.211]; P: 0.042}, troponin T [HR 1.037 (95% CI 1.009–1.683); P: 0.007], lower prealbumin [HR 0.827 (95% CI 0.224–0.988); P: 0.009] and diabetes [HR 2.103 (95% CI 1.554–3.172); P: 0.008]. Kaplan–Meier confirmed the association between CV events and YKL-40 (log rank 7.28; P = 0.007). ConclusionsYKL-40 is associated with CV events in haemodialysis patients. Higher dialysis dose and convective volume are associated with lower serum YKL-40 levels.

Development and Internal Validation of a Prediction Model to Estimate the Probability of Left-Ventricular Diastolic Dysfunction in Stable Maintenance Hemodialysis Patients without Clinical Heart Failure

Objective: To develop and internally validate a multivariable prediction model based on simple clinical record data and laboratory tests and to estimate the probability of left-ventricular diastolic dysfunction (LVDD) in stable maintenance hemodialysis (MHD) patients without clinical heart failure. Design: Cross-sectional study. Setting and Participants: In all, 181 patients on MHD without clinical heart failure were eligible from the dialysis center of Tongren Hospital, Shanghai Jiao Tong University School of Medicine between October 2017 and September 2018. Outcomes: LVDD detected by echocardiography. Measurements: We performed multivariable logistic regression using demographic, clinical, and laboratory data to identify predictors of LVDD with internal validation by using 200 bootstrap replications. Results: Overall, 78 out of 181 (43.1%) patients were affected by LVDD. Predictors included in the LVDD Model were high-sensitive cardiac troponin T (OR 5.91 per 1-ln unit; 95% CI 2.17–16.13), B-type natriuretic peptide (OR 2.35 per 1-ln unit; 95% CI 1.14–4.86), and dialysis vintage (OR 1.04 per 1-month; 95% CI 1.01–1.07). The area (AUC) under the receiver operating characteristic curve of the Model was 0.871 (95% CI 0.811–0.932, p < 0.001). The calibration plot showed good agreement between predicted and observed probabilities with a calibration slope of 1.023 and intercept of –0.010. After internal validation, the Model maintained excellent discrimination (AUC 0.858, 95% CI 0.798–0.919) and good calibration (slope of 1.079, 95% CI 1.058–1.097 and intercept of –0.120, 95% CI –0.142 to –0.093). LVDD Model <0.23 can be used to rule out (sensitivity = 87.3%, negative likelihood ratio = 12.7%) and ≥0.44 can be used to rule in (specificity = 87.6%, positive likelihood ratio = 12.4%) echocardiography diagnosed LVDD. Limitation: External validation of the Model will be required. Conclusions: A model using routinely available simple clinical record data and laboratory tests can accurately predict the risk of LVDD in stable MHD patients. The Model and its cutoff values may be useful for early diagnosis and intervention of LVDD.

Aiming for the optimal bicarbonate prescription for maintenance hemodialysis therapy in end-stage renal disease.

Acidemia and alkalemia, as a result of gradual depletion of the body's buffers followed by rapid repletion during hemodialysis (HD), are linked to adverse consequences. We examined the acid-base status with dialysis bath of higher bicarbonate (HC03- ) concentration or standard HC03- bath plus oral HC03- supplementation. A total of 60 stable HD patients (pts) were evaluated according to their pre-dialysis acid-base status both before the first and the second session of the week dialyzed against standard base dialysate of 35 mmol/L. Those who presented predialysis HC03- <22 mmol/L (25 pts) were assigned to dialysis against bath of increased HC03- levels (37 mmol/L) for 2 weeks (period A) and subsequently to dialysis with the standard dialysate bath plus daily oral sodium bicarbonate at a dose of 5 g/day for 2 weeks (period B). Pre and post-dialysis acid-base status at each study period and relevant laboratory tests were recorded. Pre-dialysis acid-base values were similar between the first and the second dialysis session. Twenty-five points had pre-dialysis pH <7.35, while 42 (the younger ones) presented pre-dialysis HC03- <22 mmol/L. After dialysis session 18 pts had pH >7.45. Comparing the two study periods, interdialytic weight was similar, pre-dialysis HC03- levels were improved with oral bicarbonate, while post-dialysis HC03- were higher during period A. Three pts could not tolerate the symptoms of alkalemia during period A. The impact of conventional HC03- concentrations of 35 mmol/L results in a considerable degree of pre-dialysis acidemia. Increasing the HC03- in bath results in more prominent post-dialysis alkalemia, however, it is not sufficient to maintain acid-base status during the interdialytic period. Oral bicarbonate supplement at a dose of 5 g/day (divided in three daily doses) results in a more balanced acid-base status, avoiding post-dialysis alkalemia.

Blood volume analysis as a guide for dry weight determination in chronic hemodialysis patients: a crossover study

BackgroundVolume overload and depletion both lead to high morbidity and mortality. Achieving euvolemia is a challenge in patients with end stage kidney disease on hemodialysis (HD). Blood volume analysis (BVA) uses radiolabeled albumin to determine intravascular blood volume (BV). The measured BV is compared to an ideal BV (validated in healthy controls). We hypothesized that BVA could be used in HD to evaluate the adequacy of the current clinically prescribed “estimated dry weight” (EDW) and to titrate EDW in order to improve overall volume status. We were also interested in the reproducibility of BVA results in end stage kidney disease.MethodsTwelve adults on chronic HD were recruited; 10 completed the study. BVA (Daxor, New York, NY, USA) was used to measure BV at baseline. EDW was kept the same if the patient was deemed to be euvolemic by BVA otherwise, the prescribed EDW was changed with the aim that measured BV would match ideal BV. A second BVA measurement was done 1–3 months later in order to measure BV again.ResultsBased on BVA, 6/10 patients were euvolemic at baseline and 5/10 were euvolemic at the second measurement. When comparing patients who had their prescribed EDW changed after the initial BVA to those who did not, both groups had similar differences between measured and ideal BV (P = 0.75). BV values were unchanged at the second measurement (P = 0.34) and there was no linear correlation between BV change and weight change (r2 = 0.08).ConclusionsThis pilot study is the first longitudinal measurement of BVA in HD patients. It revealed that changing weight did not proportionally change intravascular BV. BV remained stable for 1–3 months. BVA may not be helpful in clinically stable HD patients but studies on patients with hemodynamic instability and uncertain volume status are needed.Trial registrationClinicalTrials.gov (NCT02717533), first registered February 4, 2015.

Acute changes in cardiac structural and tissue characterisation parameters following haemodialysis measured using cardiovascular magnetic resonance

In patients with chronic kidney disease (CKD), reverse left ventricular (LV) remodelling, including reduction in LV mass, can be observed following long-term haemodialysis (HD) and has been attributed to regression of LV hypertrophy. However, LV mass can vary in response to changes in myocyte volume, edema, or fibrosis. The aims of this study were to investigate the acute changes in structural (myocardial mass and biventricular volumes) and tissue characterization parameters (native T1 and T2) following HD using cardiovascular magnetic resonance (CMR). Twenty-five stable HD patients underwent non-contrast CMR including volumetric assessment and native T1 and T2 mapping immediately pre- and post-HD. The mean time between the first and second scan was 9.1 ± 1.1 hours and mean time from completion of dialysis to the second scan was 3.5 ± 1.3 hours. Post-HD, there was reduction in LV mass (pre-dialysis 98.9 ± 36.9 g/m2 vs post-dialysis 93.3 ± 35.8 g/m2, p = 0.003), which correlated with change in body weight (r = 0.717, p < 0.001). Both native T1 and T2 reduced significantly following HD (Native T1: pre-dialysis 1085 ± 43 ms, post-dialysis 1072 ± 43 ms; T2: pre-dialysis 53.3 ± 3.0 ms, post-dialysis 51.8 ± 3.1 ms, both p < 0.05). These changes presumably reflect acute reduction in myocardial water content rather than regression of LV hypertrophy. CMR with multiparametric mapping is a promising tool to assess the cardiac changes associated with HD.

The relationship between serum bicarbonate, pH level and sleep quality in haemodialysis patients: A cross-sectional study from Turkey.

To investigate the relationship of blood pH and bicarbonate levels with sleep disorders in patients with end-stage renal disease. The cross-sectional study was conducted at Kocaeli Derince Health Practice and Research Center, Kocaeli, Turkey, in July 2015, and comprised stable haemodialysis patients aged over 18 years who had undergone at least 3 months of treatment. The Pittsburgh sleep quality index was used to assess sleep quality, and the Epworth sleepiness scale was used to assess sleepiness. Blood urea nitrogen levels were measured to determine dialysis success. SPSS 17 was used for data analysis. Of the 62 patients, 22(35.4%) were good sleepers, while 40(65.6%) were bad sleepers, and 11(17.7%) had excessive daytime sleepiness. There was no significant difference between poor and good sleepers with respect to venous pH (p=0.197) and bicarbonate (p=0.305) levels. Also, the two levels did not differ significantly between patients with routine or excessive daytime sleepiness (p>0.05). Patients with excessive daytime sleepiness had significantly lower calcium (p=0.046) and higher creatinine (p-0.014) levels and were older (p=0.01). Age was the only independent predictor of both the index and the scale scores (p<0.05 each). Sleep disorders and sleepiness were found to be high in haemodialysis patients and there was a strong correlation between sleep disturbance and age. There was no correlation of either state with patients' bicarbonate or venous pH values.

The stability and variability of serum and plasma fibroblast growth factor-23 levels in a haemodialysis cohort

BackgroundSerum fibroblast growth factor 23 (FGF-23) levels are markedly elevated in haemodialysis patients and have been linked to mortality outcomes. Small studies in health and chronic kidney disease, have demonstrated marked intra- and inter-individual variability in measured FGF-23 levels, and variable degradation in serum as compared to plasma samples. In end-stage kidney disease (ESKD), the intra- and inter-individual variability of FGF-23 levels, and the optimal collection methods remain poorly characterized. In this study we assessed the variability of FGF-23 levels in a cohort of stable haemodialysis patients. Secondly, in a subset of patients, we assessed the effects of different collection methods on measured FGF-23 levels.MethodsTo assess the variability of FGF-23, pre-dialysis blood samples were collected over 3 consecutive weeks from 75 haemodialysis patients. The effects of different specimen collection methods were examined in a subset of patients (n = 23), with pre-dialysis blood collected into different tubes: plain (serum), EDTA (plasma) and EDTA with the addition of a protease inhibitor (EDTA-PI). All analyses were performed in the main cohort and repeated in each subgroup. Variability over a 3-week period was assessed using repeated measures ANOVA and random effects linear regression models. Intra-class correlation coefficients were calculated to assess agreement, and coefficients of variation were calculated to assess intra- and inter-individual variability.ResultsOver the 3-week study period the mean FGF-23 levels were not significantly different in the serum (p = 0.26), EDTA (p = 0.62) and EDTA-PI (p = 0.55) groups. FGF-23 levels demonstrated marked intra- and inter-individual variability with a CV of 36 and 203.2%, respectively. In the subgroup analysis, the mean serum FGF-23 levels were significantly lower than the EDTA (p < 0.001) or EDTA-PI (p < 0.001) groups, however there was no difference in mean FGF-23 levels between EDTA and EDTA-PI (p = 0.54).ConclusionsThe measured FGF-23 levels were significantly lower in serum as compared to plasma, and the addition of a protease inhibitor did not confer an additional benefit. Importantly in this cohort of ESKD patients, FGF-23 levels showed marked intra- and inter-individual variability. The routine measurement of FGF-23 in ESKD remains challenging, however this study suggests the plasma is the optimal collection method for FGF-23 analysis.

Increased Weight Gain During the Long Interdialytic Period Is Associated with Minor Effects on Blood Pressure Control in Clinically Stable In-Centre Haemodialysis Patients

Background/Aims: Three-day-a-week chronic haemodialysis (cHD) involves 1 long (72 h) and 2 short (48 h) inter-dialytic periods (IDPs). We aimed to determine whether BP control following the long IDP is inferior to the short IDPs. Methods: All pre- and post-dialysis BP and weight measurements over a 4-week period were retrospectively analyzed among 135 clinically stable cHD patients at 2 academic centres with comparisons between measurements recorded following short and long IDPs. Subsequently, 23 clinically stable cHD patients underwent 24-h ambulatory blood pressure monitoring (ABPM) during the final day/night cycle of the long IDP and 1 short IDP within the same week. Results: In combined and separate analyses of the 2 retrospective cohorts, pre-dialysis BP parameters were not different following long and short IDPs despite greater inter-dialytic weight gain (IDWG) during the long IDP. Subgroup analyses of the total cohort showed no evidence for inferior BP control during the long IDP among those with high %IDWG. In the ABPM study, nocturnal hypertension and loss of nocturnal dipping were frequent. Furthermore, daytime systolic blood pressure (SBP) and pulse pressure were modestly higher during the last day/night cycle of the long compared with short IDP. Conclusion: In stable cHD patients, the greater IDWG that occurred during the long IDP was not associated with overtly inferior BP control as reflected in pre-dialysis BP measurements. However, modestly higher daytime SBP was evident towards the end of the long IDP by 24 h ABPM. Thus, while fluid gain has well-documented associations with hypertension and adverse cardiovascular outcomes, the excess IDWG that occurs during the long IDP exerts relatively minor effects on BP control in patients on well-established dialysis regimens that are better identified by ambulatory monitoring.

Oxidative Stress and Nonalcoholic Fatty Liver Disease in Hemodialysis Patients.

Introduction Nonalcoholic fatty liver disease (NAFLD) is becoming more common around the world and it may progress to cirrhosis and liver failure, increasing mortality risk. In hemodialysis (HD) patients, NAFLD may be a novel risk factor for their high cardiovascular mortality. Heightened oxidative stress is highly prevalent in HD patients. However, the relationship between oxidative stress and NAFLD in HD patients is not well defined. Methods We studied seventy-one stable nondiabetic HD patients. Nineteen patients had the diagnosis of NAFLD by ultrasonography. Blood levels of oxidative stress markers were measured in each patient, including thiobarbituric acid reactive substances (TBARS), free thiols, superoxide dismutase (SOD) activities, and glutathione peroxidase (GPx) activity. The copy numbers of mitochondrial DNA (mtDNA) in peripheral leukocytes were also determined. Demographic, biochemistry, and hemogram data were recorded. The two groups of patients were compared in order to determine the factors associated with NAFLD in HD patients. Findings Compared to those without NAFLD, nondiabetic HD patients with NAFLD had significantly higher mtDNA copy number and GPx levels. The two groups did not differ significantly in dialysis adequacy, hemoglobin, serum calcium, phosphorus, albumin, liver function tests, or lipid profiles. Regression analysis confirmed mtDNA copy numbers and GPx levels as two independent factors associated with NAFLD. Compared to those with polysulfone, patients dialyzed with cellulose membrane have significantly higher levels of TBARS. However, patients with or without NAFLD did not differ in their use of either dialysis membrane. Discussion Oxidative stress (represented by antioxidant defense, GPx) and mitochondrial DNA copy numbers are independently associated with fatty liver disease in nondiabetic HD patients. The diagnostic and therapeutic implications of this key observation warrant further exploration.

Redox State of Human Serum Albumin and Inflammatory Biomarkers in Hemodialysis Patients with Secondary Hyperparathyroidism During Oral Calcitriol Supplementation for Vitamin D.

Background:Hemodialysis (HD) patients with secondary Hyperparathyroidism (s-HPT) are exposed to increased inflammation and oxidative stress. In HD patients, oxidized albumin is a reliable marker of oxidative stress and its clinical significance has been rarely studied.Objective:The objective of this study was to evaluate Cys34 Human Serum Albumin (HSA) as oxidative stress biomarker in HD patients with s-HPT and its relationship with inflammation on bone turnover markers during oral calcitriol supplementation for vitamin D.Patients and Methods:Fifteen stable hemodialysis patients with s-HPT (mean age 48.67±8.15, 11 males and 4 females) were used in the experiment to receive calcitriol treatment for 16 weeks (0.25mcg or 0.5 mcg once a day according to serum level of Ca and P for each). The changes in the serum biochemical parameters (Ca, P, ALP, and iPTH), inflammatory markers (CRP and IL-6 levels) and serum oxidative stress condition (SOD, IS and albumin ratio HNA/HMA) were evaluated before and at 8 and 16 weeks of calcitriol treatment. The correlations between those factors were studied.Results:All patients responded to oral calcitriol therapy, with a significant decrease in the serum iPTH. The results showed that calcitriol could effectively suppress iPTH secretion with a significant elevation of serum Ca and P but ALP remained unchanged during the study. It can also effectively reduce the inflammatory markers (CRP and IL-6), while increasing the oxidative markers (SOD and IS). Oxidative albumin ratio HNA/HMA showed a significant (p=0.001) reduction after 16 weeks of calcitriol treatment and the redox state of HSA showed a positive prediction for hyperparathyroidism and for inflammation.Conclusion:The redox state of HSA could be used as a predictor for monitoring hyperparathyroidism and inflammation during calcitriol treatment by retarding albumin oxidation in HD patients with secondary hyperparathyroidism.

Bicarbonate levels in hemodialysis patients switching from lanthanum carbonate to sucroferric oxyhydroxide.

AIMTo examine possible alterations in acid-base parameters in patients switching from lanthanum carbonate (LanC) to sucroferric oxyhydroxide (SFOH).METHODSFifteen stable hemodialysis patients were switched from LanC to SFOH. Only nine continued on SFOH, three returned to LanC and the other three switched to sevelamer carbonate. The later six patients served as a control group to the SFOH group of nine patients. Blood was sampled on the 3-d and the last 2-d interval of the week prior to switching and six weeks after. Bicarbonate levels (HCO3-), pH, pO2, pCO2 were measured, and the mean of the two measurements (3-d and 2-d interval) was calculated.RESULTSComparing pre-switching to post-switching measurements in the SFOH group, no statistically significant differences were found in any of the parameters studied. The mean pre-switching HCO3- was 22.41 ± 1.66 mmol/L and the mean post-switching was 22.62 ± 2.25 mmol/L (P = 0.889). Respectively, the mean pH= 7.38 ± 0.03 vs 7.39 ± 0.03 (P = 0.635), mean pCO2= 38.41 ± 3.29 vs 38.37 ± 3.62 mmHg (P = 0.767), and Phosphate = 1.57 ± 0.27 vs 1.36 ± 0.38mmol/L (P = 0.214). There were not any significant differences when we performed the same analyses in the control group or between the SFOH group and control group. No correlations were found, either between pre-switching LanC daily dose or between post-switching daily dose of the new binder and the measured parameters.CONCLUSIONIn our small study, switching from LanC to SFOH did not have any significant effect on blood bicarbonate levels and gas analysis, indicating that there is no need to change hemodialysis prescription regarding these parameters.

Switching iron sucrose to ferric carboxymaltose associates to better control of iron status in hemodialysis patients

BackgroundAlthough the efficacy of iron sucrose (IS) and ferric carboxymaltose (FCM) in treating anemia in hemodialysis (HD) patients has been studied individually, a comparison of these two intravenous iron formulations has not yet been performed in HD patients.MethodsWe performed a retrospective audit on records of 221 stable HD patients from different HD centers in the Netherlands, who were switched from IS to FCM on a 1:1 ratio. To assess the effect of the switch on iron status parameters, data from 3 time points before and 3 time points after the switch were analyzed using linear mixed effects models. Subanalyses were done in 2 subgroups of patients anemic or iron deficient at baseline.ResultsHemoglobin increased in all groups (anemic [1.4 g/dL, P < 0.001] iron deficient [0.6 g/dL, P < 0.001]), while the weekly iron dose was significantly lower when patients received FCM compared to IS (48 vs 55 mg/week, P = 0.04). Furthermore, serum ferritin and transferrin saturation increased in all groups (anemic [64 μg/L, 5.0%, P < 0.001] iron deficient [76 μg/L, 3.6%, P < 0.001]). Finally, the darbepoetin α dose decreased significantly in all groups (anemic [− 16 μg/wk., P = 0.01] iron deficient [− 11 μg/wk., P < 0.001]).ConclusionsIn this real-life study in HD patients, a switch from IS to FCM resulted in an improvement of iron status parameters despite a lower weekly dose of FCM. Furthermore, the ESA dose was reduced during FCM, while hemoglobin levels increased.

Biological variation of procalcitonin levels in hemodialysis patients.

There is no obvious evidence regarding biological variation of procalcitonin (PCT) levels in hemodialysis (HD) patients without infections. The aim of this study was to determine the within- and between-person biological variation of PCT levels in HD patients without infections. A multicenter, prospective, cohort study enrolled 123 HD patients without any signs of infectious disease. Baseline PCT levels were determined pre- and post-HD, and then repeated pre-HD PCT measurements were performed at 2, 4, 8, 12, 16, 20, and 24 weeks after baseline blood-sampling, regardless of the presence or absence of infectious disease. Analytical variation (CVa), the within-person biological variation (CVi), between-person biological variation (CVb), individual index (II), and the reference change value (RCV) were calculated. The mean age was 62.4 years, 76.4% were male, and 32.5% had diabetes. The mean duration of HD was 87months. The median value for baseline pre-HD PCT was 0.23ng/mL, which is much higher than the reference level for healthy individuals. PCT levels decreased of 46.6% after a single HD session. CVi was 24.9%, CVb was 54.2%, II was 0.46, and RCV was calculated as 96.4% with 99% probability. The PCT level was significantly higher in stable HD patients without manifest bacterial infection. CVb was more variable than CVi in HD patients, which indicates that relative change is more important than absolute PCT levels for diagnosing bacterial infection, and doubling or more of the baseline PCT level may imply the presence of a bacterial infection in HD patients.

Phosphate control in reducing FGF23 levels in hemodialysis patients

BackgroundIn hemodialysis patients, high levels of Fibroblast Growth Factor 23 (FGF23) predict mortality. Our study was designed to test whether the control of serum phosphate is associated with a reduction in serum FGF23 levels. Additionally other variables with a potential effect on FGF23 levels were evaluated.Material and methodsThe effect of sustained (40-weeks) control of serum phosphate on FGF23 levels (intact and c-terminal) was evaluated in 21 stable hemodialysis patients that were not receiving calcimimetics or active vitamin D. Patients received non-calcium phosphate binders to maintain serum phosphate below 4.5 mg/dl. In an additional analysis, values of intact-FGF23 (iFGF23) and c-terminal FGF23 (cFGF23) from 150 hemodialysis patients were correlated with parameters of mineral metabolism and inflammation. Linear mixed models and linear regression were performed to evaluate longitudinal trajectories of variables and the association between FGF23 and the other variables examined.ResultsDuring the 40-week treatment, 12 of 21 patients achieved the target of serum phosphate <4.5 mg/dl. In these 12 patients, iFGF23 decreased to less than half whereas cFGF23 did not reduce significantly. In patients with serum phosphate >4.5 mg, iFGF23 and cFGF23 increased two and four-fold respectively as compared with baseline. Furthermore, changes in serum phosphate correlated with changes in C-reactive protein (hs-CRP). In our 150 hemodialysis patients, those in the higher tertile of serum phosphate also showed increased hs-CRP, iPTH, iFGF23 and cFGF23. Multiple regression analysis revealed that iFGF23 levels directly correlated with both serum phosphate and calcium, whereas cFGF23 correlated with serum phosphate and hs-CRP but not with calcium.ConclusionsThe control of serum phosphate reduced iFGF23. This reduction was also associated with a decreased in inflammatory parameters. Considering the entire cohort of hemodialysis patients, iFGF23 levels correlated directly with serum phosphate levels and also correlated inversely with serum calcium concentration. The levels of cFGF23 were closely related to serum phosphate and parameters of inflammation.

Intradialytic Aerobic Exercise in the United Arab Emirates: a Descriptive Study

Aim: Intradialytic exercise (IDE) improves hyperphosphatemia management in hemodialysis (HD) patient in addition to other clinical outcomes. The aim of the study is to present the strategies needed to integrate such a protocol in an HD unit in UAE and patients’ baseline characteristics.Methods: The largest HD unit in Sharjah emirate was chosen. All eligible patients (n=57) in the unit were included. Patients were stable adults HD patients who served as their own controls. The intervention included an aerobic low intensity IDE of 45 minutes per HD session, tailored to each patient’s fitness scale (BORG scale) for 6 months. Patients were educated on the importance of exercise. Outcome measures were barriers to exercise, serum phosphorus (P), urea reduction ratio (URR), malnutrition inflammation score, quality of life (QOL using euroqol5) collected at baseline and post intervention.Results: A total of 41 patients completed the study, 61% were males; 90.2%, 53.7% and 14.6% suffered from hypertension, diabetes and cardiovascular disease respectively. Hypherphosphatemia was prevalent among 75% of the patients with a mean of 5.76 ± 1.66 mg/dl. Mean age was 48 ± 14.37 years, BMI 24.98 ± 6.09 kg/m2, URR 71.88 ± 8.52%, and Kt/v 1.32 ± 1.09. The main barrier to exercise was identified to be fatigue on HD days by 58.5% of patients, followed by fear of getting hurt (36.6%). Finally, 80.4% of patients were mildly malnourished and QOL scale was 65.02% ± 18.54. Conclusion: Our study highlighted the widespread of hyperphosphatemia and malnutrition in our sample. The IDE regimen, if proven effective in future studies, could be integrated in the routine practice and may improve patients’ outcomes.

Systemic haemodynamics in haemodialysis: intradialytic changes and prognostic significance

BackgroundAlthough haemodialysis (HD) leads to alterations of systemic haemodynamics that can be monitored using dilution methods, there is a lack of data on the diagnostic and prognostic significance of haemodynamic monitoring during routine HD.MethodsIn this multicentre study, we measured cardiac index (CI), access flow (AF) and central blood volume index (CBVI) during a single HD session in stable HD patients (n = 215) using the Transonic HD03 monitor (Transonic, Ithaca, NY, USA). Systemic CI (SCI) was defined as CI corrected for AF. In a subset of patients (n = 82), total end-diastolic volume index (TEDVI) and total ejection fraction (TEF) were derived from dilution curves. Data were correlated with clinical parameters, cardiac biomarkers and bioimpedance measurements (body composition monitor; Fresenius Medical Care, Homburg, Germany). Mortality was assessed prospectively after a median follow-up of 2.6 years.ResultsMedian CI, CBVI and AF were 2.8 L/min/m2 (interquartile range 2.4–3.4), 15 mL/kg (14.5–15.7) and 980 mL/min (740–1415), respectively, at the beginning of HD. At the end of HD, CI, CBVI and AF significantly fell by −10% (−22 to 3, P < 0.0001), −9% (−23 to 3, P < 0.0001) and −4% (−13 to 5, P = 0.0004), respectively. Peripheral resistance (PR) increased slightly (P = 0.01) and blood pressure fell by −6/−3 mmHg to 128/63 mmHg (P < 0.0001). Independent predictors of ΔCI were age and ultrafiltration rate, whereas AF, overhydration and PR were protective. TEF was strongly associated with mortality [area under the dilution curve 0.77, P < 0.0001], followed by TEDVI (0.72, P = 0.0002) and SCI (0.60, P = 0.02).ConclusionsHD leads to a reduction of CI due to ultrafiltration. Haemodynamic monitoring identifies a significant number of HD patients with cardiac impairment that are at risk for increased mortality.

Low Dose Oral Iron as a Safe and Effective Iron Administration for Anemia Treatment in Hemodialysis Patients

Background: Oral Ferric Citrate (FC) is an effective iron therapy in hemodialysis patients. We investigated the effect of oral iron on anemia in hemodialysis patients focusing on different effects between sodium ferrous citrate (SF) and FC and dose effect of SF.Methods: Study 1; FC was administered (1500 mg/day) either as a de novo iron administration (Group D) or after a switch from SF (50 mg/day) (Group S). Dose of erythropoietin stimulating agent (ESA), serum hemoglobin levels, ESA/hemoglobin ratio and iron states were investigated for 64 weeks retrospectively. Study 2; 23 stable hemodialysis patients with long-term 50 mg/day of SF were randomly divided to two groups; dose was increased to 150 mg/day (Group 150) and unchanged in the rest (Group 50). Without changing the dose of ESA, hemoglobin levels and iron states were compared for 40 weeks prospectively. Results: Study 1; data were obtained from 28 patients. FC administration increased ferritin levels in both groups (median; Group D; 0W: 49.3, 56W: 214.0, Group S; 0W: 120.0, 56W: 217.0 ng/mL), but hemoglobin levels increased and ESA dose and ESA/hemoglobin ratio decreased only in Group D (0W vs. 12W: p < 0.05). Study 2; 17 patients completed the study. Although higher dose of SF resulted in increased ferritin and hepcidin-25 levels in Group 150 (p < 0.05 and < 0.01, respectively), hemoglobin levels did not change in either group.Conclusions: Instable hemodialysis patients, 50 mg/day of SF have a comparable effect on anemia to that of 1500 mg/day of FC or 150 mg/day of SF with less increase in serum ferritin levels.

Effect of high amylose resistant starch (HAM-RS2) supplementation on biomarkers of inflammation and oxidative stress in hemodialysis patients: a randomized clinical trial.

Systemic inflammation and oxidative stress play a central role in the pathogenesis of cardiovascular disease and numerous other complications of CKD. Recent studies demonstrated that consumption of a diet enriched with amylose (HAM-RS2), attenuates oxidative stress and inflammation, and improves intestinal microbiome in CKD rats. The present study was designed to explore the effect of dietary amylose supplementation in hemodialysis patients. Forty-six stable hemodialysis patients were randomized to receive biscuits containing 20 g/day during the first four weeks and 25 g/day in the next four weeks of either HAM-RS2 or wheat-flour. Fasting predialysis blood samples obtained before, during and at the end of trial were processed for biomarkers of oxidative stress and inflammation. There was no significant difference in baseline clinical or biochemical parameters between the two groups. Serum levels of TNF-α, IL-6, and malondialdehyde declined significantly (P < 0.05) in the HAM-RS2-treated group but remained unchanged in the placebo-treated group. No significant difference was observed in serum Interleukin-1β (IL-1β) and hs-CRP concentrations and total antioxidant activity between two groups. Serum urea and creatinine concentrations significantly declined and severity of constipation improved in HAM-RS2-treated patients (P < 0.05). HAM-RS2 consumption was well tolerated and did not cause discernible side effects. Administration of HAM-RS2 for eight weeks significantly reduced levels of inflammatory and oxidative markers in hemodialysis patients confirming the results observed in CKD animals. Long term trials are needed to explore the impact of HAM-RS2 supplementation on clinical outcomes in end stage renal disease population.

The effect of isohydric hemodialysis on the binding and removal of uremic retention solutes.

BackgroundThere is growing evidence that the accumulation of protein- bound uremic retention solutes, such as indoxyl sulfate, p-cresyl sulfate and kynurenic acid, play a role in the accelerated cardiovascular disease seen in patients undergoing chronic hemodialysis. Protein-binding, presumably to albumin, renders these solutes poor-dialyzable.We previously observed that the free fraction of indoxyl sulfate was markedly reduced at the end of hemodialysis. We hypothesized that solute binding might be pH-dependent and attributed the changes in free solute concentration to the higher serum pH observed at the end of standard hemodialysis with dialysis buffer bicarbonate concentration greater than 35 mmol/L. We observed that acidification of uremic plasma to pH 6 in vitro greatly increased the proportion of freeIS.MethodsWe tested our hypothesis by reducing the dialysate bicarbonate buffer concentration to 25 mmol/L for the initial half of the hemodialysis treatment (“isohydric dialysis”). Eight stable hemodialysis patients underwent “isohydric dialysis” for 90 minutes and then were switched to standard buffer (bicarbonate = 37mmol/L). A second dialysis, 2 days later, employed standard buffer throughout.ResultsWe found a clearcut separation of blood pH and bicarbonate concentrations after 90 minutes of “isohydric dialysis” (pH = 7.37, bicarbonate = 22.4 mmol/L) and standard dialysis (pH = 7.49, bicarbonate = 29.0 mmol/L). Binding affinity varied widely among the 10 uremic retention solutes analyzed. Kynurenic acid (0.05 free), p-cresyl sulfate (0.12 free) and indoxyl sulfate (0.13 free) demonstrated the greatest degree of binding. Three solutes (indoxyl glucuronide, p-cresyl glucuronide, and phenyl glucuronide) were virtually unbound. Analysis of free and bound concentrations of uremic retention solutes confirmed our prediction that binding of solute is affected by pH. However, in a mixed models analysis, we found that the reduction in total uremic solute concentration during dialysis accounted for a greater proportion of the variation in free concentration, presumably an effect of saturation binding to albumin, than did the relatively small change in pH produced by isohydric dialysis. The effect of pH on binding appeared to be restricted to those solutes most highly protein-bound.The solutes most tightly bound exhibited the lowest dialyzer clearances. An increase in dialyzer clearance during isohydric and standard dialyses was statistically significant only for kynurenic acid.ConclusionThese findings provide evidence that the binding of uremic retention solutes is influenced by pH. The effect of reducing buffer bicarbonate concentration (“isohydric dialysis:”), though significant, was small but may be taken to suggest that further modification of dialysis technique that would expose blood to a greater decrease in pH would lead to a greater increase the free fraction of solute and enhance the efficacy of hemodialysis in the removal of highly protein-bound uremic retention solutes.