End-Stage Renal Disease Patients Lose a Substantial Amount of Amino Acids during Hemodialysis.
ABSTRACT: BACKGROUND:Poor nutritional status is frequently observed in end-stage renal disease patients and associated with adverse clinical outcomes and increased mortality. Loss of amino acids (AAs) during hemodialysis (HD) may contribute to protein malnutrition in these patients. OBJECTIVE:We aimed to assess the extent of AA loss during HD in end-stage renal disease patients consuming their habitual diet. METHODS:Ten anuric chronic HD patients (mean ± SD age: 67.9 ± 19.3 y, BMI: 23.2 ± 3.5 kg/m2), undergoing HD 3 times per week, were selected to participate in this study. Spent dialysate was collected continuously and plasma samples were obtained directly before and after a single HD session in each participant. AA profiles in spent dialysate and in pre-HD and post-HD plasma were measured through ultra-performance liquid chromatography to determine AA concentrations and, as such, net loss of AAs. In addition, dietary intake before and throughout HD was assessed using a 24-h food recall questionnaire during HD. Paired-sample t tests were conducted to compare pre-HD and post-HD plasma AA concentrations. RESULTS:During an HD session, 11.95 ± 0.69 g AAs were lost via the dialysate, of which 8.26 ± 0.46 g were nonessential AAs, 3.69 ± 0.31 g were essential AAs, and 1.64 ± 0.17 g were branched-chain AAs. As a consequence, plasma total and essential AA concentrations declined significantly from 2.88 ± 0.15 and 0.80 ± 0.05 mmol/L to 2.27 ± 0.11 and 0.66 ± 0.05 mmol/L, respectively (P < 0.05). AA profiles of pre-HD plasma and spent dialysate were similar. Moreover, AA concentrations in pre-HD plasma and spent dialysate were strongly correlated (Spearman's ? = 0.92, P < 0.001). CONCLUSIONS:During a single HD session, ?12 g AAs are lost into the dialysate, causing a significant decline in plasma AA concentrations. AA loss during HD can contribute substantially to protein malnutrition in end-stage renal disease patients. This study was registered at the Netherlands Trial Registry (NTR7101).
Project description:End stage renal disease (ESRD) patients are characterized by increased morbidity and mortality due to highest prevalence of cardiovascular disease. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that controls cellular signaling in human physiology, pathophysiology, and diseases. Increased MIF plasma levels promote vascular inflammation and development of atherosclerosis. We have shown that MIF is associated with vascular dysfunction in ESRD patients. Whether hemodialysis (HD) affects circulating MIF plasma levels is unknown. We here aimed to investigate whether HD influences the circulating MIF pool in ESRD patients.An observational single-center study was conducted. MIF plasma levels in ESRD patients were assessed before, during, and after a HD session (n = 29). Healthy age-matched volunteers served as controls to compare correlations of MIF plasma levels with inflammatory plasma components (n = 20). MIF removed from the circulating blood pool could be detected in the dialysate and allowed for calculation of totally removed MIF (MIF content in dialysate 219±4 ?g/HD-session). MIF plasma levels were markedly decreased 2 hour after initiation of HD (MIF plasma level pre-HD 84.8±6 ng/ml to intra-HD 61.2±5 ng/ml p<0.001) and were replenished already 20 min after termination of HD to basal levels (intra-HD 61.2±5 ng/ml to post-HD 79.8±5 ng/ml, p<0.001).MIF is a dialyzable plasma component that is effectively filtrated during HD from the patient blood pool in large amounts. After removal of remarkable amounts of MIF during a single HD session, MIF plasma pool is early reconstituted after termination of HD from unknown sources.
Project description:Cool dialysate is often recommended for prevention of intra-dialytic hypotensive episodes in maintenance hemodialysis (HD) patients. However, its effect on toxin removal is not studied. It is known that inter-compartmental resistance is the main barrier for toxin removal. Cool dialysate can potentially increase this resistance by vasoconstriction and thus impair the toxin removal. The aim of this trial is to compare the toxin removal outcome associated with cool vs. warm dialysate.This study is based on the hypothesis that dialysate temperature, a potential maneuver to maintain hemodynamic stability during HD, may influence inter-compartmental resistance and hence, toxin removal. Only stable HD patients will be recruited for this study. The quantum of removed toxins will be assessed by the total spent dialysate, which is a gold standard to quantify the efficacy of a single dialysis session. Collected samples will be analyzed for urea, creatinine, phosphate, ?2-microglobulin, and uric acid. The study is a single center, self-controlled, randomized prospective clinical research where 20 study subjects will undergo 2 dialysis sessions: (a) cool dialysis with dialysate at 35.5°C, and (b) warm dialysis with dialysate at 37°C. Pre- and post-dialysis blood samples will be collected to quantify the dialysis adequacy and toxin reduction ratio.This is the first clinical research to investigate the effect of dialysate temperature on removal of both small and large-sized toxins. Successful completion of this research will provide important knowledge pertaining to dialysate temperature prescription. Results can also lead to the hypothesis that cool dialysate may help in by preventing intra-dialytic hypotensive episodes, but prolonged prescription of cool dialysate may lead to comorbidities associated with excess toxin accumulation. The new knowledge will encourage for personalized dialysate temperature profiling.Clinicaltrials.gov Identifier--NCT02064153.
Project description:BACKGROUND:Fluid overload is frequent among hemodialysis (HD) patients. Dialysis therapy itself may favor sodium imbalance from sodium dialysate prescription. As on-line hemodiafiltration (OL-HDF) requires large amounts of dialysate infusion, this technique can expose to fluid accumulation in case of a positive sodium gradient between dialysate and plasma. To evaluate this risk, we have analyzed and compared the fluid status of patients treated with HD or OL-HDF in French NephroCare centers. METHOD:This is a cross-sectional and retrospective analysis of prevalent dialysis patients. Data were extracted from the EUCLID5 data base. Patients were split in 2 groups (HD and OL-HDF) and compared as whole group or matched patients for fluid status criteria including predialysis relative fluid overload (RelFO%) status from the BCM®. RESULTS:2242 patients (age 71 years; female: 39%; vintage: 38 months; Charlson index: 6) were studied. 58% of the cohort were prescribed post-dilution OL-HDF. Comparing the HD and OL-HDF groups, there was no difference between HD and OL-HDF patients regarding the predialysis systolic BP, the interdialytic weight gain, the dialysate-plasma sodium gradient, and the predialysis RelFO%. The stepwise logistic regression did not find dialysis modality (HD or OL-HDF) associated with fluid overload or high predialysis systolic blood pressure. In OL-HDF patients, monthly average convective or weekly infusion volumes per session were not related with the presence of fluid overload. CONCLUSIONS:In this cross-sectional study we did not find association between the use of post-dilution OL-HDF and markers of fluid volume excess. Aligned dialysis fluid sodium concentrations to patient predialysis plasma sodium and regular monitoring of fluid volume status by bioimpedance spectroscopy may have been helpful to manage adequately the fluid status in both OL-HDF and HD patients.
Project description:<h4>Background</h4>Observational studies of hemodialysis patients treated thrice weekly have shown that serum and dialysate potassium and bicarbonate concentrations are associated with patient outcomes. The effect of more frequent hemodialysis on serum potassium and bicarbonate concentrations has rarely been studied, especially for treatments at low dialysate flow rate.<h4>Methods</h4>These post-hoc analyses evaluated data from patients who transferred from in-center hemodialysis (HD) to daily HD at low dialysate flow rates during the FREEDOM Study. The primary outcomes were the change in predialysis serum potassium and bicarbonate concentrations after transfer from in-center HD (mean during the last 3?months) to daily HD (mean during the first 3?months).<h4>Results</h4>After transfer from in-center HD to daily HD (data from 345 patients, 51?±?15?years of age, mean?±?standard deviation), predialysis serum potassium decreased (P?<?0.001) by approximately 0.4?mEq/L when dialysate potassium concentration during daily HD was 1?mEq/L; no change occurred when dialysate potassium concentration during daily HD was 2?mEq/L. After transfer from in-center HD to daily HD (data from 284 patients, 51?±?15?years of age), predialysis serum bicarbonate concentration decreased (P?=?0.0022) by 1.0?±?3.3?mEq/L when dialysate lactate concentration was 40?mEq/L but increased (P?<?0.001) by 2.5?±?3.5?mEq/L when dialysate lactate concentration was 45?mEq/L. These relationships were dependent on serum potassium and bicarbonate concentrations during in-center HD.<h4>Conclusions</h4>Control of serum potassium and bicarbonate concentrations during daily HD at low dialysate flow rates is readily achievable; the choice of dialysate potassium and lactate concentration can be informed when transfer is from in-center HD to daily HD.
Project description:BACKGROUND:Sudden cardiac death is one of the primary causes of mortality in chronic hemodialysis (HD) patients. Prolonged QTc interval is associated with increased rate of sudden cardiac death. The aim of this article is to assess the abnormalities found in electrocardiograms (ECGs), and to explore factors that can influence the QTc interval. METHODS:A total of 141 conventional HD patients were enrolled in this study. ECG tests were conducted on each patient before a single dialysis session and 15 minutes before the end of dialysis session (at peak stress). Echocardiography tests were conducted before dialysis session began. Blood samples were drawn by phlebotomy immediately before and after the dialysis session. RESULTS:Before dialysis, 93.62% of the patients were in sinus rhythm, and approximately 65% of the patients showed a prolonged QTc interval (i.e., a QTc interval above 440 ms in males and above 460ms in females). A comparison of ECG parameters before dialysis and at peak stress showed increases in heart rate (77.45±11.92 vs. 80.38±14.65 bpm, p = 0.001) and QTc interval (460.05±24.53 ms vs. 470.93±24.92 ms, p<0.001). After dividing patients into two groups according to the QTc interval, lower pre-dialysis serum concentrations of potassium (K+), calcium (Ca2+), phosphorus, calcium* phosphorus (Ca*P), and higher concentrations of plasma brain natriuretic peptide (BNP) were found in the group with prolonged QTc intervals. Patients in this group also had a larger left atrial diameter (LAD) and a thicker interventricular septum, and they tended to be older than patients in the other group. Then patients were divided into two groups according to ?QTc (?QTc = QTc peak-stress- QTc pre-HD). When analyzing the patients whose QTc intervals were longer at peak stress than before HD, we found that they had higher concentrations of Ca2+ and P5+ and lower concentrations of K+, ferritin, UA, and BNP. They were also more likely to be female. In addition, more cardiac construction abnormalities were found in this group. In multiple regression analyses, serum Ca2+ concentration before HD and LAD were independent variables of QTc interval prolongation. UA, ferritin, and interventricular septum were independent variables of ?QTc. CONCLUSION:Prolonged QT interval is very common in HD patients and is associated with several risk factors. An appropriate concentration of dialysate electrolytes should be chosen depending on patients' clinical conditions.
Project description:Haemodialysis (HD) patients suffer from an increased risk of cardiovascular disease (CVD). Skin autofluorescence (SAF) is a strong marker for CVD. SAF indirectly measures tissue advanced glycation end products (AGE) being cumulative metabolites of oxidative stress and cytokine-driven inflammatory reactions. The dialysates often contain glucose.Autofluorescence of skin and plasma (PAF) were measured in patients on HD during standard treatment (ST) with a glucose-containing dialysate (n?=?24). After that the patients were switched to a glucose-free dialysate (GFD) for a 2-week period. New measurements were performed on PAF and SAF after 1 week (M1) and 2 weeks (M2) using GFD. Nonparametric paired statistical analyses were performed between each two periods.SAF after HD increased non-significantly by 1.2% while when a GFD was used during HD at M1, a decrease of SAF by 5.2% (p?=?0.002) was found. One week later (M2) the reduction of 1.6% after the HD was not significant (p?=?0.33). PAF was significantly reduced during all HD sessions. Free and protein-bound PAF decreased similarly whether glucose containing or GFD was used. The HD resulted in a reduction of the total PAF of approximately 15%, the free compound of 20% and the protein bound of 10%. The protein bound part of PAF corresponded to approximately 56% of the total reduction. The protein bound concentrations after each HD showed the lowest value after 2 weeks using glucose-free dialysate (p?<?0.05). The change in SAF could not be related to a change in PAF.When changing to a GFD, SAF was reduced by HD indicating that such measure may hamper the accumulation and progression of deposits of AGEs to protein in tissue, and thereby also the development of CVD. Glucose-free dialysate needs further attention. Protein binding seems firm but not irreversible.ISRCTN registry: ISRCTN13837553 . Registered 16/11/2016 (retrospectively registered).
Project description:In the United States, hemodialysis (HD) is generally performed via a bicarbonate dialysate. It is not known if small amounts of acid used in dialysate to buffer the bicarbonate can meaningfully contribute to overall buffering administered during HD. We aimed to investigate the metabolism of acetate with use of two different acid buffer concentrates and determine if it effects blood bicarbonate concentrations in HD patients.The Acid-Base Composition with use of hemoDialysates (ABChD) trial was a Phase IV, prospective, single blind, randomized, cross-over, 2 week investigation of peridialytic dynamics of acetate and bicarbonate associated with use of acid buffer concentrates. Eleven prevalent HD patients participated from November 2014 to February 2015. Patients received two HD treatments, with NaturaLyte® and GranuFlo® acid concentrates containing 4 and 8 mEq/L of acetate, respectively. Dialysate order was chosen in a random fashion. The endpoint was to characterize the dynamics of acetate received and metabolized during hemodialysis, and how it effects overall bicarbonate concentrations in the blood and dialysate. Acetate and bicarbonate concentrations were assessed before, at 8 time points during, and 6 time points after the completion of HD.Data from 20 HD treatments for 11 patients (10 NaturaLyte® and 10 GranuFlo®) was analyzed. Cumulative trajectories of arterialized acetate were unique between NaturaLyte® and GranuFlo® (p = 0.003), yet individual time points demonstrated overlap without remarkable differences. Arterialized and venous blood bicarbonate concentrations were similar at HD initiation, but by 240 min into dialysis, mean arterialized bicarbonate concentrations were 30.2 (SD ± 4.16) mEq/L in GranuFlo® and 28.8 (SD ± 4.26) mEq/L in NaturaLyte®. Regardless of acid buffer concentrate, arterial blood bicarbonate was primarily dictated by the prescribed bicarbonate level. Subjects tolerated HD with both acid buffer concentrates without experiencing any related adverse events.A small fraction of acetate was delivered to HD patients with use of NaturaLyte® and GranuFlo® acid buffers; the majority of acetate received was observed to be rapidly metabolized and cleared from the circulation. Blood bicarbonate concentrations appear to be determined mainly by the prescribed concentration of bicarbonate.This trial was registered on ClinicalTrials.gov on 11 Dec 2014 ( NCT02334267 ).
Project description:Hemodialysis (HD) is a treatment given to patients with renal failure. Notable treatment-related complications include hypotension, cramps, insufficient blood flow, and arrhythmia. Most complications are associated with unstable blood pressure during HD. Physicians are devoted to seeking solutions to prevent or lower the incidence of possible complications. With advances in technology, big data have been obtained in various medical fields. The accumulated dialysis records in each HD session can be gathered to obtain big HD data with the potential to assist HD staff in increasing patient wellbeing. We generated a large stream of HD parameters collected from dialysis equipment associated with the Vital Info Portal gateway and correlated with the demographic data stored in the hospital information system from each HD session. We expect that the application of HD big data will greatly assist HD staff in treating intradialytic hypotension, setting optimal dialysate parameters, and even developing an intelligent early-warning system as well as providing individualized suggestions regarding dialysis settings in the future.
Project description:Amino acid (AA) concentrations are influenced by both exogenous (e.g. diet, lifestyle) and endogenous factors (e.g. genetic, transcriptomic, epigenetic, and metabolomic). Fasting plasma AA profiles in adulthood are predictive of diabetes risk over periods of up to 12 years. Data on AA profiles in cross-generational cohorts, including individuals from shared gene-environment settings are scarce, but would allow the identification of the contribution of heritable and environmental factors characterising the levels of circulating AAs. This study aimed to investigate parent-child (familial dyad) concordance, absolute differences between generations- (children versus adults), age- (in adults: 28-71 years), and sex-dependent differences in plasma AA concentrations. Plasma AA concentrations were measured by UHPLC/MS-MS in 1166 children [mean (SD) age 11 (0.5) years, 51% female] and 1324 of their parents [44 (5.1) years, 87% female]. AA concentrations were variably concordant between parents and their children (5-41% of variability explained). Most AA concentrations were higher in adults than children, except for the non-essential AAs arginine, aspartic acid, glutamine, hydroxy-proline, proline, and serine. Male adults and children typically had higher AA concentrations than females. The exceptions were alanine, glutamine, glycine, hydroxy-proline, serine, and threonine in girls; and glycine and serine in women. Age, sex, and shared familial factors are important determinants of plasma AA concentrations.
Project description:Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) experience enhanced oxidative stress and systemic inflammation, which are risk factors for cardiovascular disease, the most common cause of excess morbidity and mortality for these patients. Different pathways producing different types of oxidative stress occur in ESRD. The purpose of our study was to determine the effect of HD on plasma levels of protein-bound dityrosine (di-Tyr), a biomarker of protein oxidation.Protein-bound di-Tyr formation was measured by size exclusion HPLC coupled to fluorescence detector. Clinical laboratory parameters were measured by standardized methods.In most ESRD patients, a single HD session decreased significantly the plasma protein-bound di-Tyr level, although the mean post-HD level remained significantly greater than the one in healthy people. Furthermore, pre-HD plasma protein-bound di-Tyr level was positively correlated with pre-HD serum creatinine and albumin concentrations. No significant correlation was found between plasma protein-bound di-Tyr level and serum concentration of C-reactive protein, a biomarker of systemic inflammation.This study demonstrates that a single HD session does not increase, rather partially decreases, oxidative pathways producing di-Tyr in the haemodialyzed patient.The choice of the most pertinent biomarkers of oxidative stress is critical for the development of novel treatments for ESRD. However, the relative importance of oxidative stress and inflammation in ESRD remains largely undetermined, and several questions concerning oxidative stress and inflammation remain poorly defined. These results could stimulate further studies on the use of plasma protein-bound di-Tyr as a long-lasting oxidative stress biomarker in ESRD.