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Haemodialysis with Tinzaparin Versus Dialysate Citrate as Anticoagulation.
Mahmood, D, Stegmayr, BG
Blood purification. 2018;(3):257-263
Abstract
Anticoagulation with citrate-containing haemodialysate (cHD) is an alternative to tinzaparin haemodialysate (tHD). The study investigated whether cHD would differ when changed from tHD. The same 18 patients were their own controls followed up with cHD for 5 months. LDL-cholesterol decreased at the end of a cHD session (p = 0.01). Neutrophils (p = 0.013) and monocytes (p = 0.007) dropped more during a cHD session. During the follow-up period of cHD, approximately 50% needed additional tinzaparin. Before the cHD session could start, there was a lower total cholesterol at 2 weeks (p = 0.014) and LDL-cholesterol at 1 month (p = 0.011) versus an increase of LDL at 5 months (p = 0.02). Only patients without additional tinzaparin had a reduction of -C-reactive protein (CRP) at 2 months of cHD (p < 0.05) but not later. Solely cHD seems possible only in half of the patients. A greater reduction in granulocytes and monocytes during cHD indicates a more extensive blood membrane interaction, while CRP may be lower.
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Pharmacokinetics, Biotransformation, and Excretion of [14C]Etelcalcetide (AMG 416) Following a Single Microtracer Intravenous Dose in Patients with Chronic Kidney Disease on Hemodialysis.
Subramanian, R, Zhu, X, Hock, MB, Sloey, BJ, Wu, B, Wilson, SF, Egbuna, O, Slatter, JG, Xiao, J, Skiles, GL
Clinical pharmacokinetics. 2017;(2):179-192
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Abstract
Etelcalcetide (AMG 416) is a novel synthetic peptide calcium-sensing receptor activator in clinical development as an intravenous calcimimetic for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on hemodialysis. Etelcalcetide is composed of seven D-aminoacids with an L-cysteine linked to a D-cysteine by a disulfide bond. A single intravenous dose of [14C]etelcalcetide (10 mg; 26.3 kBq; 710 nCi) was administered to patients with CKD on hemodialysis to elucidate the pharmacokinetics, biotransformation, and excretion of etelcalcetide in this setting. Blood, dialysate, urine, and feces were collected to characterize the pharmacokinetics, biotransformation product profiles, mass balance, and formation of anti-etelcalcetide antibodies. Accelerator mass spectrometry was necessary to measure the microtracer quantities of C-14 excreted in the large volumes of dialysate and other biomatrices. An estimated 67 % of the [14C]etelcalcetide dose was recovered in dialysate, urine, and feces 176 days after dose administration. Etelcalcetide was primarily cleared by hemodialysis, with approximately 60 % of the administered dose eliminated in dialysate. Minor excretion was observed in urine and feces. Biotransformation resulted from disulfide exchange with endogenous thiols, and preserved the etelcalcetide D-amino acid backbone. Drug-related radioactivity circulated primarily as serum albumin peptide conjugate (SAPC). Following removal of plasma etelcalcetide by hemodialysis, re-equilibration occurred between SAPC and L-cysteine present in blood to partially restore the etelcalcetide plasma concentrations between dialysis sessions. No unanticipated safety signals or anti-etelcalcetide or anti-SAPC antibodies were detected.
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Longitudinal Trend in Lipid Profile of Incident Peritoneal Dialysis Patients is Not Influenced by the Use of Biocompatible Solutions.
Cho, Y, Büchel, J, Steppan, S, Passlick-Deetjen, J, Hawley, CM, Dimeski, G, Clarke, M, Johnson, DW, ,
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 2016;(2):146-53
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Abstract
UNLABELLED ♦ BACKGROUND The longitudinal trends of lipid parameters and the impact of biocompatible peritoneal dialysis (PD) solutions on these levels remain to be fully defined. The present study aimed to a) evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solutions on serum lipid parameters, and b) explore the capacity of lipid parameters (total cholesterol [TC], triglyceride [TG], high density lipoprotein [HDL], TC/HDL, low density lipoprotein [LDL], very low density lipoprotein [VLDL]) to predict cardiovascular events (CVE) and mortality in PD patients. ♦ METHODS The study included 175 incident participants from the balANZ trial with at least 1 stored serum sample. A composite CVE score was used as a primary clinical outcome measure. Multilevel linear regression and Poisson regression models were fitted to describe the trend of lipid parameters over time and its ability to predict composite CVE, respectively. ♦ RESULTS Small but statistically significant increases in serum TG (coefficient 0.006, p < 0.001), TC/HDL (coefficient 0.004, p = 0.001), and VLDL cholesterol (coefficient 0.005, p = 0.001) levels and a decrease in the serum HDL cholesterol levels (coefficient -0.004, p = 0.009) were observed with longer time on PD, whilst the type of PD solution (biocompatible vs standard) received had no significant effect on these levels. Peritoneal dialysis glucose exposure was significantly associated with trends in TG, TC/HDL, HDL and VLDL levels. Baseline lipid parameter levels were not predictive of composite CVEs or all-cause mortality. ♦ CONCLUSION Serum TG, TC/HDL, and VLDL levels increased and the serum HDL levels decreased with increasing PD duration. None of the lipid parameters were significantly modified by biocompatible PD solution use over the time period studied or predictive of composite CVE or mortality.
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Effects of a new bicarbonate/lactate-buffered neutral peritoneal dialysis fluid for peritoneal failure in patients undergoing peritoneal dialysis.
Hoshino, T, Ishii, H, Kitano, T, Shindo, M, Miyazawa, H, Yamada, H, Ito, K, Ueda, Y, Kaku, Y, Hirai, K, et al
Discovery medicine. 2016;(114):81-8
Abstract
BACKGROUND The highly concentrated lactate in peritoneal dialysis fluid (PDF) has been considered to contribute to peritoneal failure in patients undergoing PD. A new PDF containing a lower lactate concentration, physiological bicarbonate concentration, and neutral pH (bicarbonate/lactate-buffered neutral PDF) was recently developed. We compared the clinical effects of this bicarbonate/lactate-buffered neutral PDF and a lactate-buffered neutral PDF. METHODS AND DESIGN Patients undergoing PD were changed from a lactate-buffered neutral PDF to a bicarbonate/lactate-buffered neutral PDF. We then investigated the changes in peritoneal functions as estimated by a peritoneal equilibration test (PET) and the following surrogate markers of peritoneal membrane failure in the drained dialysate: fibrin degradation products (FDP), vascular endothelial growth factor (VEGF), cancer antigen 125 (CA125), interleukin-6 (IL-6), and transforming growth factor beta 1 (TGF-β1). RESULTS Fourteen patients undergoing PD were enrolled. The PET results were not different before and after use of the bicarbonate/lactate-buffered neutral PDF. The FDP concentration significantly decreased from 15.60 ± 13.90 to 6.04 ± 3.49 μg/mL (p = 0.02) and the VEGF concentration significantly decreased from 37.83 ± 15.82 to 27.70 ± 3.80 pg/mL (p = 0.02), while the CA125 and IL-6 concentrations remained unchanged before and after use of the bicarbonate/lactate-buffered neutral PDF. TGF-β1 was not detected in most patients. CONCLUSION The bicarbonate/lactate-buffered neutral PDF decreased the FDP and VEGF concentrations in the drained dialysate. These results suggest that the decreased lactate level achieved by administration of bicarbonate with a neutral pH in PDF may contribute to decreased peritoneal membrane failure in patients undergoing PD.
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Icodextrin reduces insulin resistance in non-diabetic patients undergoing automated peritoneal dialysis: results of a randomized controlled trial (STARCH).
de Moraes, TP, Andreoli, MC, Canziani, ME, da Silva, DR, Caramori, JC, Ponce, D, Cassi, HV, de Andrade Bastos, K, Rio, DR, Pinto, SW, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2015;(11):1905-11
Abstract
BACKGROUND Insulin resistance is a common risk factor in chronic kidney disease patients contributing to the high cardiovascular burden, even in the absence of diabetes. Glucose-based peritoneal dialysis (PD) solutions are thought to intensify insulin resistance due to the continuous glucose absorption from the peritoneal cavity. The aim of our study was to analyse the effect of the substitution of glucose for icodextrin on insulin resistance in non-diabetic PD patients in a multicentric randomized clinical trial. METHODS This was a multicenter, open-label study with balanced randomization (1:1) and two parallel-groups. Inclusion criteria were non-diabetic adult patients on automated peritoneal dialysis (APD) for at least 3 months on therapy prior to randomization. Patients assigned to the intervention group were treated with 2L of icodextrin 7.5%, and the control group with glucose 2.5% during the long dwell and, at night in the cycler, with a prescription of standard glucose-based PD solution only in both groups. The primary end-point was the change in insulin resistance measured by homeostatic model assessment (HOMA) index at 90 days. RESULTS Sixty patients were included in the intervention (n = 33) or the control (n = 27) groups. There was no difference between groups at baseline. After adjustment for pre-intervention HOMA index levels, the group treated with icodextrin had the lower post-intervention levels at 90 days in both intention to treat [1.49 (95% CI: 1.23-1.74) versus 1.89 (95% CI: 1.62-2.17)], (F = 4.643, P = 0.03, partial η(2) = 0.078); and the treated analysis [1.47 (95% CI: 1.01-1.84) versus 2.18 (95% CI: 1.81-2.55)], (F = 7.488, P = 0.01, partial η(2) = 0.195). CONCLUSIONS The substitution of glucose for icodextrin for the long dwell improved insulin resistance measured by HOMA index in non-diabetic APD patients.
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Removal characteristics and total dialysate content of glutamine and other amino acids in critically ill patients with acute kidney injury undergoing extended dialysis.
Schmidt, JJ, Hafer, C, Spielmann, J, Hadem, J, Schönenberger, E, Schmidt, BM, Kielstein, JT
Nephron. Clinical practice. 2014;(1):62-6
Abstract
BACKGROUND Acute kidney injury in critically ill patients is associated with the activation of protein catabolism and a negative nitrogen balance. Renal replacement therapy (RRT) aggravates this problem by eliminating a substantial amount of amino acids. However, there is scarce data on the removal characteristics of modern dialysis membranes in extended dialysis. METHODS This is a prospective study in 10 extended dialysis sessions using a 1.8-m(2) polysulfone membrane (EMiC2 dialyzer or AV 1000S; FMC, Germany). Blood samples for 19 amino acids were drawn before, during, and after 10 h of extended dialysis (blood/dialysate flow 150 ml/min). In addition, samples for the calculation of dialyzer clearance and samples from the total spent dialysate were measured using a Biochrom 30 amino acid analyzer. RESULTS Despite no significant difference in pre- and postdialysis plasma amino acid levels, we found an impressive amount of amino acids in collected spent dialysate, i.e. 10.5 g/10 h of treatment. The dialyzer clearance ranged from 67.6 ml/min for phenylalanine to 140.0 ml/min for valine. The total eliminated masses of the measured amino acids had equal values for both membranes. There was a significant difference between the dialyzer clearance of the investigated membranes for glutamine (AV 1000S: 83.3 ml/min vs. EMiC2: 92.0 ml/min, p = 0.02) and serine (88.8 ml/min vs. 91.8 ml/min, p = 0.005). DISCUSSION Our data indicate that the modern forms of RRT eliminate amino acids to an extent that has not been met by our nutritional support standards. Especially the removal of glutamine, important for immune function and cell regeneration, might have detrimental effects on the recovery of critically ill patients.
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Post-dilution on line haemodiafiltration with citrate dialysate: first clinical experience in chronic dialysis patients.
Panichi, V, Fiaccadori, E, Rosati, A, Fanelli, R, Bernabini, G, Scatena, A, Pizzarelli, F
TheScientificWorldJournal. 2013;:703612
Abstract
BACKGROUND Citrate has anticoagulative properties and favorable effects on inflammation, but it has the potential hazards of inducing hypocalcemia. Bicarbonate dialysate (BHD) replacing citrate for acetate is now used in chronic haemodialysis but has never been tested in postdilution online haemodiafiltration (OL-HDF). METHODS Thirteen chronic stable dialysis patients were enrolled in a pilot, short-term study. Patients underwent one week (3 dialysis sessions) of BHD with 0.8 mmol/L citrate dialysate, followed by one week of postdilution high volume OL-HDF with standard bicarbonate dialysate, and one week of high volume OL-HDF with 0.8 mmol/L citrate dialysate. RESULTS In citrate OL-HDF pretreatment plasma levels of C-reactive protein and β 2-microglobulin were significantly reduced; intra-treatment plasma acetate levels increased in the former technique and decreased in the latter. During both citrate techniques (OL-HDF and HD) ionized calcium levels remained stable within the normal range. CONCLUSIONS Should our promising results be confirmed in a long-term study on a wider population, then OL-HDF with citrate dialysate may represent a further step in improving dialysis biocompatibility.
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Relationship between Icodextrin use and decreased level of small low-density lipoprotein cholesterol fractioned by high-performance gel permeation chromatography.
Kanda, E, Ai, M, Iwamoto, A, Okazaki, M, Maeda, Y, Sasaki, S, Yoshida, M
BMC nephrology. 2013;:234
Abstract
BACKGROUND Because of the absorption of glucose in peritoneal dialysis (PD) solution, PD patients show an atherogenic lipid profile, which is predictive of poor survival in PD patients. Lipoprotein subclasses consist of a continuous spectrum of particles of different sizes and densities (fraction). In this study, we investigated the lipoprotein fractions in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level, and evaluated the effects of icodextrin on lipid metabolism. METHODS Forty-nine PD patients were enrolled in this cross-sectional study in Japan. The proportions of cholesterol levels to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions were measured using an improved method of high-performance gel permeation chromatography (HPGPC). RESULTS Twenty-six patients used icodextrin. Although no significant differences in cholesterol levels in LDL and high-density lipoprotein (HDL) were observed between the patients using icodextrin (icodextrin group) and control groups, HPGPC showed that the icodextrin group had significantly lower cholesterol proportions in the small LDL (t-test, p=0.053) and very small LDL (p=0.019), and significantly higher cholesterol proportions in the very large HDL and large HDL than the control group (p=0.037; p=0.066, respectively). Multivariate analysis adjusted for patient characteristics and statin use showed that icodextrin use was negatively associated with the cholesterol proportions in the small LDL (p=0.037) and very small LDL (p=0.026), and positively with those in the very large HDL (p=0.040), large HDL (p=0.047), and medium HDL (p=0.009). CONCLUSIONS HPGPC showed the relationship between icodextrin use and the cholesterol proportions in lipoprotein fractions in PD patients. These results suggest that icodextrin may improve atherogenic lipid profiles in a manner different from statin.
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Biocompatibility of dialysis fluid for online HDF.
Tomo, T, Shinoda, T
Contributions to nephrology. 2011;:89-98
Abstract
We investigated the effects of online hemodiafiltration (HDF) using acetate-free bicarbonate dialysis (AFD) fluid on bioincompatibility as represented by inflammatory markers in patients undergoing maintenance hemodialysis therapy and compared it with conventional acetate-containing bicarbonate dialysis (ACD) fluid. A total of 24 maintenance hemodialysis patients were registered for cross-over design during the 6-month study period (13 males and 11 females, aged 58.2 ± 14.5 years, mean duration of dialysis 10.0 ± 8.0 years, chronic glomerular nephritis in 20 patients, diabetic nephropathy in 2 patients, polycystic kidney in 1 patient, and nephrosclerosis in 1 patient). These patients were subjected to ACD for the first 3 months followed by AFD fluid for the latter 3 months. Blood variables of C-reactive protein and interleukin-6 were determined after each of the first and latter 3-month periods. The filters (membrane surface area, raw material), the conditions of HDF (blood flow rate, dialysate flow rate, dialysis time, dry weight, pre-dilution mode and convective volume) and drug regimen including erythrocyte-simulating agent (drug type, dosage) were unchanged throughout the cross-over study. There appeared to be significantly higher levels of predialysis blood pH and bicarbonate in the AFD phase than in the ACD phase. Blood C-reactive protein and interleukin-6 levels were significantly decreased in AFD group as compared with those seen in ACD group. From these results, it can be suggested that online HDF using AFD fluid contributes to alleviating microinflammation, a prognostic factor for bioincompatible events in hemodialysis patients.
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Effect of lowering dialysate sodium concentration on interdialytic weight gain and blood pressure in patients undergoing thrice-weekly in-center nocturnal hemodialysis: a quality improvement study.
Munoz Mendoza, J, Bayes, LY, Sun, S, Doss, S, Schiller, B
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2011;(6):956-63
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BACKGROUND Patients on in-center nocturnal hemodialysis therapy typically experience higher interdialytic weight gain (IDWG) than patients on conventional hemodialysis therapy. We determined the safety and effects of decreasing dialysate sodium concentration on IDWG and blood pressure in patients on thrice-weekly in-center nocturnal hemodialysis therapy. STUDY DESIGN Quality improvement, pre-post intervention. SETTINGS & PARTICIPANTS 15 participants in a single facility. QUALITY IMPROVEMENT PLAN Participants underwent three 12-week treatment phases, each with different dialysate sodium concentrations, as follows: phase A, 140 mEq/L; phase B, 136 or 134 mEq/L; and phase A(+), 140 mEq/L. Participants were blinded to the exact timing of the intervention. OUTCOMES IDWG, IDWG/dry weight (IDWG%), and blood pressure. MEASUREMENTS Outcome data were obtained during the last 2 weeks of each phase and compared with mixed models. The fraction of sessions with adverse events (eg, cramping and hypotension) also was reported. RESULTS IDWG, IDWG%, and predialysis systolic blood pressure decreased significantly by 0.6 ± 0.6 kg, 0.6% ± 0.8%, and 8.3 ± 14.9 mm Hg, respectively, in phase B compared with phase A (P < 0.05 for all comparisons). No differences in predialysis diastolic and mean arterial or postdialysis blood pressures were found (P > 0.05 for all comparisons). The proportion of treatments with intradialytic hypotension was low and similar in each phase (P = 0.9). In phase B compared with phase A, predialysis plasma sodium concentration was unchanged (P > 0.05), whereas postdialysis plasma sodium concentration decreased by 3.7 ± 1.9 mEq/L (P < 0.05). LIMITATIONS Modest sample size. CONCLUSION Decreasing dialysate sodium concentrations in patients undergoing thrice-weekly in-center nocturnal hemodialysis resulted in a clinical and statistically significant decrease in IDWG, IDWG%, postdialysis plasma sodium concentration, and predialysis systolic blood pressure without increasing adverse events. Prolonged exposure to higher than required dialysate sodium concentrations may drive IDWG and counteract some of the purported benefits of "go-slow" (longer session length) hemodialysis.