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John K. Leypoldt - One of the best experts on this subject based on the ideXlab platform.
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Removal of vancomycin administered during dialysis by a high-flux Dialyzer.
Hemodialysis international. International Symposium on Home Hemodialysis, 2018Co-Authors: Heather Nyman, John K. Leypoldt, Adhish Agarwal, Harry O. Senekjian, Alfred K CheungAbstract:Introduction Hemodialysis patients frequently receive vancomycin for treatment of gram-positive bacterial infections. This drug is most conveniently administered in outpatient dialysis units during the hemodialysis treatment. However, there is a paucity of data on the removal of vancomycin by high-flux polyamide Dialyzers. Methods This is a prospective crossover study in which seven uninfected chronic hemodialysis patients at three dialysis units received vancomycin 1 gram intravenously over one hour immediately after the dialysis treatment (Phase 1), and vancomycin 1.5 grams during the last hour of dialysis treatment using a polyarylethersulfone, polyvinylpyrrolidone, polyamide high-flux (Polyflux 24R) Dialyzer (Phase 2). There was a three-week washout period between phases. Serial serum vancomycin concentrations were used to determine the removal of vancomycin when administered during dialysis. Findings Dialysis removed 35 ± 15% (range 18-56%) of the vancomycin dose when administered during the last hour of dialysis. The calculated area under the curve (AUC) of vancomycin levels for 0-44.5 hours from the start of infusion were similar between the two phases (AUCPhase 1 884 ± 124 mg-hr/L, mean ± SD; AUCPhase 2 856 ± 208 mg-hr/L; P=0.72). Serum vancomycin concentrations immediately prior to the next dialysis treatment following vancomycin administration were also similar between the two phases (13.1 ± 2.7 mg/L in Phase 1 and 12.3 ± 3.3 mg/L in Phase 2; P=0.55). Discussion When using a polyarylethersulfone, polyvinylpyrrolidone, and polyamide high-flux HD membrane with a 24R Polyflux Dialyzer, vancomycin can be administered during the last hour of dialysis if the dose that is prescribed for intra-dialysis dosing is empirically increased to account for intra-dialytic drug removal.
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Dialyzer membranes as determinants of the adequacy of dialysis
Seminars in Nephrology, 2005Co-Authors: Madhukar Chelamcharla, John K. Leypoldt, Alfred K CheungAbstract:Hemodialysis membranes have undergone a gradual but substantial evolution over the past few decades. Classification of modern Dialyzer membranes by chemical composition bears little relationship to their functional characteristics. The fundamental properties that determine the capacity of the membrane to remove solutes and fluids are its surface area, thickness, pore size, pore density, and potential to adsorb proteins. Dialyzer membrane performance is characterized clinically by its efficiency, defined as the potential to remove urea and presented as the mass-transfer area coefficient (KoA) and ultrafiltration coefficient (K uf ),defined as the potential to remove water adjusted for the transmembrane pressure. The parameter K uf usually, but not invariably, correlates with the membrane permeability, defined as the potential to remove middle molecules, with β 2 -microglobulin being the currently popular marker. The sieving coefficient reflects the membrane potential to transport solutes by convection and is particularly useful for hemofiltration. Enhancing solute clearance is accomplished clinically by increasing blood and dialysate flow rates, strategies that also are applicable to middle molecules for highly permeable membranes. Novel designs of Dialyzers include the optimization of fluid flow path geometry and increasing the membrane pore selectivity for solutes by using nanotechnology.
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effect of low dialysate flow rate on hemoDialyzer mass transfer area coefficients for urea and creatinine
Home hemodialysis international. International Symposium on Home Hemodialysis, 1999Co-Authors: John K. Leypoldt, Alfred K CheungAbstract:: Recent work has shown that the Dialyzer mass transfer area coefficient (Ko A) for urea increases when the dialysate flow rate is increased from 500 to 800 mL/min. In this study we determined urea and creatinine clearances for two commercial Dialyzers containing polysulfone hollow fibers in vitro at 37°C, a nominal blood flow rate of 300 mL/ min, and dialysate flow rates (Qd ) ranging from 100 to 800 mL/min. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from solute concentrations in the input and output flows on both the blood and dialysate sides. Urea and creatinine Ko A values, calculated from the mean of the blood and dialysate side clearances, increased (p < 0.01) with increasing Qd over the entire range studied. The increase in both urea and creatinine Ko A with increasing Qd was proportional to the Ko A value. These data show that changes in Qd alter small solute clearances greater than predicted assuming a constant Ko A.
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effects of hemoDialyzer reuse on clearances of urea and β2 microglobulin
Journal of The American Society of Nephrology, 1999Co-Authors: Alfred K Cheung, Lawrence Y Agodoa, John T. Daugirdas, Tom Greene, Nathan W Levin, Thomas A Depner, Frank A Gotch, John K. LeypoldtAbstract:Although Dialyzer reuse in chronic hemodialysis pa- tients is commonly practiced in the United States, performance of reused Dialyzers has not been extensively and critically evaluated. The present study analyzes data extracted from a multicenter clinical trial (the HEMO Study) and examines the effect of reuse on urea and b2-microglobulin (b2M) clearance by low-flux and high-flux Dialyzers reprocessed with various germicides. The Dialyzers evaluated contained either modified cellulosic or polysulfone membranes, whereas the germicides examined included peroxyacetic acid/acetic acid/hydrogen per- oxide combination (Renalin ® ), bleach in conjunction with formaldehyde, glutaraldehyde or Renalin, and heated citric acid. Clearance of b2M decreased, remained unchanged, or increased substantially with reuse, depending on both the membrane material and the reprocessing technique. In contrast, urea clearance decreased only slightly (approximately 1 to 2% per 10 reuses), albeit statistically significantly with reuse, regardless of the porosity of the membrane and reprocessing method. Inasmuch as patient survival in the chronic hemodi- alysis population is influenced by clearances of small solutes and middle molecules, precise knowledge of the membrane material and reprocessing technique is important for the pre- scription of hemodialysis in centers practicing reuse. High-flux hemoDialyzers and reuse of Dialyzers have been widely used for decades, yet the effects of these practices on solute clearances have not been fully evaluated. Although the beneficial effect of increasing urea clearance on clinical outcome has been established, at least up to a single-pool Kt/V value of 1.2 (1), there are also accumulating data suggesting that the removal of middle molecules (using vitamin B12 as marker) influences patient survival (2,3). Thus, maintenance of the clearance of both small and large solutes for reused Dialyzers is important. Reuse can affect Dialyzer performance in at least two different ways. The first is the result of deposition of blood elements inside the lumen of the blood compartment and onto the Dialyzer mem- brane. The second is the result of the reprocessing procedure. At present, the popular germicides used in reprocessing in the United States are Renalin (made up of peroxyacetic acid, acetic acid, and hydrogen peroxide, Minntech, Minneapolis, MN), formaldehyde, and glutaraldehyde (4). To enhance the aesthetic appearance of the Dialyzers during reuse, sodium hypochlorite (bleach) is often used in conjunction with formaldehyde or glutaraldehyde to re- move residual blood proteins. More recently, heated citric acid has also been introduced to clean and disinfect Dialyzers for reuse. Because the chemical composition and mechanical structure are vastly different among various types of dialysis membranes, their interactions with the blood elements and reprocessing agents are likely to differ as well. The HEMO Study is a prospective randomized multicenter trial sponsored by the U.S. National Institutes of Health designed to examine the effects of urea Kt/V and the type of dialysis mem- brane on clinical outcome of chronic hemodialysis patients (5). Various models of Dialyzers and reprocessing methods are used among the 15 clinical centers (more than 45 dialysis units) in the trial. Using this large database, we have prospectively examined the effects of various combinations of Dialyzers and reprocessing agents on the clearance of urea and b2-microglobulin (b2M). The data show that the effects of reuse on b2M are far more drastic than those on urea clearance. Furthermore, the effects vary greatly depending on the dialysis membrane material and reprocessing reagents. These observations confirm and extend our fundamental understanding of alterations in Dialyzer performance during reuse.
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effect of hemoDialyzer reuse dissociation between clearances of small and large solutes
American Journal of Kidney Diseases, 1998Co-Authors: John K. Leypoldt, Alfred K Cheung, R B DeeterAbstract:Abstract Dialyzers are reused in approximately three quarters of the dialysis units in the United States, but the effect of reprocessing on Dialyzer performance has not been extensively evaluated. In a crossover study of six chronic hemodialysis patients, we determined urea, creatinine, phosphate, and beta2-microglobulin clearances and dialysate protein loss for two types of low-flux and two types of high-flux Dialyzers during use numbers 1, 2, 5, and 15. Dialyzers were reprocessed by an automated machine using Renalin (Renal Systems, Plymouth, MN) as the germicide. Dialyzer arterial and venous blood and dialysate outflow samples were obtained at 5 and 180 minutes of each dialysis session to evaluate solute clearances. Urea, creatinine, and phosphate clearances were calculated using dialysate concentrations, whereas beta2- microglobulin clearance was calculated using plasma concentrations to include its removal by adsorption to the dialysis membrane. There was a trend for urea, creatinine, and phosphate clearances to decrease with reuse for both low-flux and high-flux Dialyzers, but these differences were not statistically significant. The clearance of beta2- microglobulin and dialysate total protein concentration was small for low-flux Dialyzers; these values were not dependent on reuse. There was a trend for beta2-microglobulin clearance and dialysate total protein concentration to decrease during a dialysis treatment using high-flux Dialyzers. More significantly, beta2-microglobulin clearance and dialysate total protein concentration decreased substantially with the reuse of high-flux Dialyzers. These observations show that the maintenance of small solute clearances during reuse of high-flux Dialyzers does not ensure the maintenance of large solute clearances. (Am J Kidney Dis 1998 Aug;32(2):295-301)
Alfred K Cheung - One of the best experts on this subject based on the ideXlab platform.
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Removal of vancomycin administered during dialysis by a high-flux Dialyzer.
Hemodialysis international. International Symposium on Home Hemodialysis, 2018Co-Authors: Heather Nyman, John K. Leypoldt, Adhish Agarwal, Harry O. Senekjian, Alfred K CheungAbstract:Introduction Hemodialysis patients frequently receive vancomycin for treatment of gram-positive bacterial infections. This drug is most conveniently administered in outpatient dialysis units during the hemodialysis treatment. However, there is a paucity of data on the removal of vancomycin by high-flux polyamide Dialyzers. Methods This is a prospective crossover study in which seven uninfected chronic hemodialysis patients at three dialysis units received vancomycin 1 gram intravenously over one hour immediately after the dialysis treatment (Phase 1), and vancomycin 1.5 grams during the last hour of dialysis treatment using a polyarylethersulfone, polyvinylpyrrolidone, polyamide high-flux (Polyflux 24R) Dialyzer (Phase 2). There was a three-week washout period between phases. Serial serum vancomycin concentrations were used to determine the removal of vancomycin when administered during dialysis. Findings Dialysis removed 35 ± 15% (range 18-56%) of the vancomycin dose when administered during the last hour of dialysis. The calculated area under the curve (AUC) of vancomycin levels for 0-44.5 hours from the start of infusion were similar between the two phases (AUCPhase 1 884 ± 124 mg-hr/L, mean ± SD; AUCPhase 2 856 ± 208 mg-hr/L; P=0.72). Serum vancomycin concentrations immediately prior to the next dialysis treatment following vancomycin administration were also similar between the two phases (13.1 ± 2.7 mg/L in Phase 1 and 12.3 ± 3.3 mg/L in Phase 2; P=0.55). Discussion When using a polyarylethersulfone, polyvinylpyrrolidone, and polyamide high-flux HD membrane with a 24R Polyflux Dialyzer, vancomycin can be administered during the last hour of dialysis if the dose that is prescribed for intra-dialysis dosing is empirically increased to account for intra-dialytic drug removal.
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Dialyzer membranes as determinants of the adequacy of dialysis
Seminars in Nephrology, 2005Co-Authors: Madhukar Chelamcharla, John K. Leypoldt, Alfred K CheungAbstract:Hemodialysis membranes have undergone a gradual but substantial evolution over the past few decades. Classification of modern Dialyzer membranes by chemical composition bears little relationship to their functional characteristics. The fundamental properties that determine the capacity of the membrane to remove solutes and fluids are its surface area, thickness, pore size, pore density, and potential to adsorb proteins. Dialyzer membrane performance is characterized clinically by its efficiency, defined as the potential to remove urea and presented as the mass-transfer area coefficient (KoA) and ultrafiltration coefficient (K uf ),defined as the potential to remove water adjusted for the transmembrane pressure. The parameter K uf usually, but not invariably, correlates with the membrane permeability, defined as the potential to remove middle molecules, with β 2 -microglobulin being the currently popular marker. The sieving coefficient reflects the membrane potential to transport solutes by convection and is particularly useful for hemofiltration. Enhancing solute clearance is accomplished clinically by increasing blood and dialysate flow rates, strategies that also are applicable to middle molecules for highly permeable membranes. Novel designs of Dialyzers include the optimization of fluid flow path geometry and increasing the membrane pore selectivity for solutes by using nanotechnology.
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effect of low dialysate flow rate on hemoDialyzer mass transfer area coefficients for urea and creatinine
Home hemodialysis international. International Symposium on Home Hemodialysis, 1999Co-Authors: John K. Leypoldt, Alfred K CheungAbstract:: Recent work has shown that the Dialyzer mass transfer area coefficient (Ko A) for urea increases when the dialysate flow rate is increased from 500 to 800 mL/min. In this study we determined urea and creatinine clearances for two commercial Dialyzers containing polysulfone hollow fibers in vitro at 37°C, a nominal blood flow rate of 300 mL/ min, and dialysate flow rates (Qd ) ranging from 100 to 800 mL/min. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from solute concentrations in the input and output flows on both the blood and dialysate sides. Urea and creatinine Ko A values, calculated from the mean of the blood and dialysate side clearances, increased (p < 0.01) with increasing Qd over the entire range studied. The increase in both urea and creatinine Ko A with increasing Qd was proportional to the Ko A value. These data show that changes in Qd alter small solute clearances greater than predicted assuming a constant Ko A.
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effects of hemoDialyzer reuse on clearances of urea and β2 microglobulin
Journal of The American Society of Nephrology, 1999Co-Authors: Alfred K Cheung, Lawrence Y Agodoa, John T. Daugirdas, Tom Greene, Nathan W Levin, Thomas A Depner, Frank A Gotch, John K. LeypoldtAbstract:Although Dialyzer reuse in chronic hemodialysis pa- tients is commonly practiced in the United States, performance of reused Dialyzers has not been extensively and critically evaluated. The present study analyzes data extracted from a multicenter clinical trial (the HEMO Study) and examines the effect of reuse on urea and b2-microglobulin (b2M) clearance by low-flux and high-flux Dialyzers reprocessed with various germicides. The Dialyzers evaluated contained either modified cellulosic or polysulfone membranes, whereas the germicides examined included peroxyacetic acid/acetic acid/hydrogen per- oxide combination (Renalin ® ), bleach in conjunction with formaldehyde, glutaraldehyde or Renalin, and heated citric acid. Clearance of b2M decreased, remained unchanged, or increased substantially with reuse, depending on both the membrane material and the reprocessing technique. In contrast, urea clearance decreased only slightly (approximately 1 to 2% per 10 reuses), albeit statistically significantly with reuse, regardless of the porosity of the membrane and reprocessing method. Inasmuch as patient survival in the chronic hemodi- alysis population is influenced by clearances of small solutes and middle molecules, precise knowledge of the membrane material and reprocessing technique is important for the pre- scription of hemodialysis in centers practicing reuse. High-flux hemoDialyzers and reuse of Dialyzers have been widely used for decades, yet the effects of these practices on solute clearances have not been fully evaluated. Although the beneficial effect of increasing urea clearance on clinical outcome has been established, at least up to a single-pool Kt/V value of 1.2 (1), there are also accumulating data suggesting that the removal of middle molecules (using vitamin B12 as marker) influences patient survival (2,3). Thus, maintenance of the clearance of both small and large solutes for reused Dialyzers is important. Reuse can affect Dialyzer performance in at least two different ways. The first is the result of deposition of blood elements inside the lumen of the blood compartment and onto the Dialyzer mem- brane. The second is the result of the reprocessing procedure. At present, the popular germicides used in reprocessing in the United States are Renalin (made up of peroxyacetic acid, acetic acid, and hydrogen peroxide, Minntech, Minneapolis, MN), formaldehyde, and glutaraldehyde (4). To enhance the aesthetic appearance of the Dialyzers during reuse, sodium hypochlorite (bleach) is often used in conjunction with formaldehyde or glutaraldehyde to re- move residual blood proteins. More recently, heated citric acid has also been introduced to clean and disinfect Dialyzers for reuse. Because the chemical composition and mechanical structure are vastly different among various types of dialysis membranes, their interactions with the blood elements and reprocessing agents are likely to differ as well. The HEMO Study is a prospective randomized multicenter trial sponsored by the U.S. National Institutes of Health designed to examine the effects of urea Kt/V and the type of dialysis mem- brane on clinical outcome of chronic hemodialysis patients (5). Various models of Dialyzers and reprocessing methods are used among the 15 clinical centers (more than 45 dialysis units) in the trial. Using this large database, we have prospectively examined the effects of various combinations of Dialyzers and reprocessing agents on the clearance of urea and b2-microglobulin (b2M). The data show that the effects of reuse on b2M are far more drastic than those on urea clearance. Furthermore, the effects vary greatly depending on the dialysis membrane material and reprocessing reagents. These observations confirm and extend our fundamental understanding of alterations in Dialyzer performance during reuse.
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effect of hemoDialyzer reuse dissociation between clearances of small and large solutes
American Journal of Kidney Diseases, 1998Co-Authors: John K. Leypoldt, Alfred K Cheung, R B DeeterAbstract:Abstract Dialyzers are reused in approximately three quarters of the dialysis units in the United States, but the effect of reprocessing on Dialyzer performance has not been extensively evaluated. In a crossover study of six chronic hemodialysis patients, we determined urea, creatinine, phosphate, and beta2-microglobulin clearances and dialysate protein loss for two types of low-flux and two types of high-flux Dialyzers during use numbers 1, 2, 5, and 15. Dialyzers were reprocessed by an automated machine using Renalin (Renal Systems, Plymouth, MN) as the germicide. Dialyzer arterial and venous blood and dialysate outflow samples were obtained at 5 and 180 minutes of each dialysis session to evaluate solute clearances. Urea, creatinine, and phosphate clearances were calculated using dialysate concentrations, whereas beta2- microglobulin clearance was calculated using plasma concentrations to include its removal by adsorption to the dialysis membrane. There was a trend for urea, creatinine, and phosphate clearances to decrease with reuse for both low-flux and high-flux Dialyzers, but these differences were not statistically significant. The clearance of beta2- microglobulin and dialysate total protein concentration was small for low-flux Dialyzers; these values were not dependent on reuse. There was a trend for beta2-microglobulin clearance and dialysate total protein concentration to decrease during a dialysis treatment using high-flux Dialyzers. More significantly, beta2-microglobulin clearance and dialysate total protein concentration decreased substantially with the reuse of high-flux Dialyzers. These observations show that the maintenance of small solute clearances during reuse of high-flux Dialyzers does not ensure the maintenance of large solute clearances. (Am J Kidney Dis 1998 Aug;32(2):295-301)
Sirak Petros - One of the best experts on this subject based on the ideXlab platform.
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myoglobin clearance with continuous veno venous hemodialysis using high cutoff Dialyzer versus continuous veno venous hemodiafiltration using high flux Dialyzer a prospective randomized controlled trial
Critical Care, 2020Co-Authors: Lorenz Weidhase, Thorsten Kaiser, Jonathan De Fallois, Elena Hausig, Meinhard Mende, Sirak PetrosAbstract:Myoglobin clearance in acute kidney injury requiring renal replacement therapy is important because myoglobin has direct renal toxic effects. Clinical data comparing different modalities of renal replacement therapy addressing myoglobin clearance are limited. This study aimed to compare two renal replacement modalities regarding myoglobin clearance. In this prospective, randomized, single-blinded, single-center trial, 70 critically ill patients requiring renal replacement therapy were randomized 1:1 into an intervention arm using continuous veno-venous hemodialysis with high cutoff Dialyzer and a control arm using continuous veno-venous hemodiafiltration postdilution with high-flux Dialyzer. Regional citrate anticoagulation was used in both groups to maintain the extracorporeal circuit. The concentrations of myoglobin, urea, creatinine, β2-microglobulin, interleukin-6 and albumin were measured before and after the Dialyzer at 1 h, 6 h, 12 h, 24 h and 48 h after initiating continuous renal replacement therapy. Thirty-three patients were allocated to the control arm (CVVHDF with high-flux Dialyzer) and 35 patients to the intervention arm (CVVHD with high cutoff Dialyzer). Myoglobin clearance, as a primary endpoint, was significantly better in the intervention arm than in the control arm throughout the whole study period. The clearance values for urea and creatinine were higher in the control arm. There was no measurable albumin clearance in both arms. The clearance data for β2-microglobulin and interleukin-6 were non-inferior in the intervention arm compared to those for the control arm. Dialyzer lifespan was 57.0 [38.0, 72.0] hours in the control arm and 70.0 [56.75, 72.0] hours in the intervention arm (p = 0.029). Myoglobin clearance using continuous veno-venous hemodialysis with high cutoff Dialyzer and regional citrate anticoagulation is better than that with continuous veno-venous hemodiafiltration with regional citrate anticoagulation. German Clinical Trials Registry (DRKS00012407); date of registration 23/05/2017. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012407 .
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middle molecule clearance with high cut off Dialyzer versus high flux Dialyzer using continuous veno venous hemodialysis with regional citrate anticoagulation a prospective randomized controlled trial
PLOS ONE, 2019Co-Authors: Lorenz Weidhase, Elena Haussig, Stephan Haussig, Thorsten Kaiser, Jonathan De Fallois, Sirak PetrosAbstract:Background Regional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends Dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off Dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques. Methods In this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux Dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off Dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-Dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD. Results Mean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p<0.001). For myoglobin (8.0±4.5 ml/min vs. 0.2±3.6 ml/min, p<0.001) and IL-6 (1.5±4.3 vs. -2.5±3.5 ml/min, p = 0.002) a higher mean plasma clearance using high-cut-off Dialyzer could be detected too, but no difference for urea, creatinine and albumin could be observed concerning this parameter between the two groups. Conclusion CVVHD using a high cut-off Dialyzer results in more effective middle molecule clearance than that with high-flux Dialyzer. Trial registration German Clinical Trials Register (DRKS00005254, registered 26th November 2013)
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Middle molecule clearance with high cut-off Dialyzer versus high-flux Dialyzer using continuous veno-venous hemodialysis with regional citrate anticoagulation: A prospective randomized controlled trial
2019Co-Authors: Lorenz Weidhase, Elena Haussig, Stephan Haussig, Thorsten Kaiser, Jonathan De Fallois, Sirak PetrosAbstract:BackgroundRegional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends Dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off Dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques.MethodsIn this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux Dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off Dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-Dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD.ResultsMean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p
Lorenz Weidhase - One of the best experts on this subject based on the ideXlab platform.
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myoglobin clearance with continuous veno venous hemodialysis using high cutoff Dialyzer versus continuous veno venous hemodiafiltration using high flux Dialyzer a prospective randomized controlled trial
Critical Care, 2020Co-Authors: Lorenz Weidhase, Thorsten Kaiser, Jonathan De Fallois, Elena Hausig, Meinhard Mende, Sirak PetrosAbstract:Myoglobin clearance in acute kidney injury requiring renal replacement therapy is important because myoglobin has direct renal toxic effects. Clinical data comparing different modalities of renal replacement therapy addressing myoglobin clearance are limited. This study aimed to compare two renal replacement modalities regarding myoglobin clearance. In this prospective, randomized, single-blinded, single-center trial, 70 critically ill patients requiring renal replacement therapy were randomized 1:1 into an intervention arm using continuous veno-venous hemodialysis with high cutoff Dialyzer and a control arm using continuous veno-venous hemodiafiltration postdilution with high-flux Dialyzer. Regional citrate anticoagulation was used in both groups to maintain the extracorporeal circuit. The concentrations of myoglobin, urea, creatinine, β2-microglobulin, interleukin-6 and albumin were measured before and after the Dialyzer at 1 h, 6 h, 12 h, 24 h and 48 h after initiating continuous renal replacement therapy. Thirty-three patients were allocated to the control arm (CVVHDF with high-flux Dialyzer) and 35 patients to the intervention arm (CVVHD with high cutoff Dialyzer). Myoglobin clearance, as a primary endpoint, was significantly better in the intervention arm than in the control arm throughout the whole study period. The clearance values for urea and creatinine were higher in the control arm. There was no measurable albumin clearance in both arms. The clearance data for β2-microglobulin and interleukin-6 were non-inferior in the intervention arm compared to those for the control arm. Dialyzer lifespan was 57.0 [38.0, 72.0] hours in the control arm and 70.0 [56.75, 72.0] hours in the intervention arm (p = 0.029). Myoglobin clearance using continuous veno-venous hemodialysis with high cutoff Dialyzer and regional citrate anticoagulation is better than that with continuous veno-venous hemodiafiltration with regional citrate anticoagulation. German Clinical Trials Registry (DRKS00012407); date of registration 23/05/2017. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012407 .
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middle molecule clearance with high cut off Dialyzer versus high flux Dialyzer using continuous veno venous hemodialysis with regional citrate anticoagulation a prospective randomized controlled trial
PLOS ONE, 2019Co-Authors: Lorenz Weidhase, Elena Haussig, Stephan Haussig, Thorsten Kaiser, Jonathan De Fallois, Sirak PetrosAbstract:Background Regional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends Dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off Dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques. Methods In this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux Dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off Dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-Dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD. Results Mean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p<0.001). For myoglobin (8.0±4.5 ml/min vs. 0.2±3.6 ml/min, p<0.001) and IL-6 (1.5±4.3 vs. -2.5±3.5 ml/min, p = 0.002) a higher mean plasma clearance using high-cut-off Dialyzer could be detected too, but no difference for urea, creatinine and albumin could be observed concerning this parameter between the two groups. Conclusion CVVHD using a high cut-off Dialyzer results in more effective middle molecule clearance than that with high-flux Dialyzer. Trial registration German Clinical Trials Register (DRKS00005254, registered 26th November 2013)
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Middle molecule clearance with high cut-off Dialyzer versus high-flux Dialyzer using continuous veno-venous hemodialysis with regional citrate anticoagulation: A prospective randomized controlled trial
2019Co-Authors: Lorenz Weidhase, Elena Haussig, Stephan Haussig, Thorsten Kaiser, Jonathan De Fallois, Sirak PetrosAbstract:BackgroundRegional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends Dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off Dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques.MethodsIn this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux Dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off Dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-Dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD.ResultsMean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p
John T. Daugirdas - One of the best experts on this subject based on the ideXlab platform.
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quantifying the effect of plasma viscosity on in vivo Dialyzer performance
Asaio Journal, 2020Co-Authors: Daniel Schneditz, John T. DaugirdasAbstract:Dialyzer manufacturers characterize performance of their devices based on measurements of clearance using crystalloid solutions. Typically, in vitro Dialyzer mass transfer area coefficients for urea (K0A) are substantially higher than values measured in vivo. The reason for this reduction has not been clearly determined. We hypothesized that the known effect of viscosity on reducing solute diffusivity might partially or fully account for this reduction. In vitro Dialyzer clearances of urea, glucose, and lactate were measured using crystalloid solutions as well as bovine blood with varying hematocrit and plasma viscosity under a wide range of operating conditions. Viscosities of crystalloid solutions, of blood plasma, and of whole blood were measured at 37°C at a shear rate of 100/s. Diffusivity and relative K0A values (K0Arel) in eight Dialyzers were computed for each solute under these different conditions. Plasma was 1.84 times more viscous compared with crystalloid solution (ηrel = 1.84), suggesting a correction multiplier of 1/ηrel = 0.54 for in vivo K0A relative to the in vitro value. Experimental K0Arel at that ηrel was on average reduced to 52% of crystalloid in vitro K0A values. The multiplier 0.52 measured in this study is close to the multiplier 0.55 predicted for average plasma viscosities and also close to the multiplier 0.54 assumed for urea kinetic modeling to provide reasonable urea distribution volumes. The known effect of viscosity on solute diffusivity is therefore sufficient to explain the reduction in Dialyzer K0A for urea and glucose in vivo compared with in vitro measurements.
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hemodialysis effect on platelet count and function and hemodialysis associated thrombocytopenia
Kidney International, 2012Co-Authors: John T. Daugirdas, Angelito A BernardoAbstract:Substantial activation of platelets can occur in the course of hemodialysis. Platelet surface markers show evidence of platelet degranulation. Some activation occurs due to exposure of blood to the roller pump segment and microbubbles may play a role. Platelet activation seems to be reduced with reused Dialyzers or with those containing synthetic versus cellulosic membranes. Nevertheless, a substantial degree of platelet activation can be demonstrated with polysulfone and other synthetic membranes; the amount of activation may differ substantially among polysulfone membranes, depending on the manufacturer and the polyvinylpyrrolidone content. Platelet–platelet and platelet–leukocyte aggregates have been detected in the Dialyzer blood outflow line and the consequences of these to the microcirculation are unknown. Typically, the platelet count decreases slightly during the first hour of dialysis, but mostly returns to initial values by the end of dialysis. A number of chronic hemodialysis patient cases have been reported in which a marked decrease in platelet count (50% or more) during dialysis was observed, resulting in mild degrees of predialysis thrombocytopenia. In only one case was the decrease in platelet count associated with bleeding. Dialyzer hypersensitivity symptoms are infrequently associated with a fall in platelet count. Most recent cases of dialysis-associated thrombocytopenia have been with polysulfone membranes, especially polysulfone membranes sterilized by electron beam. The exact cause of these reactions remains unknown.
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mortality risk by hemoDialyzer reuse practice and Dialyzer membrane characteristics results from the usrds dialysis morbidity and mortality study
American Journal of Kidney Diseases, 2001Co-Authors: Friedrich K Port, Lawrence Y Agodoa, John T. Daugirdas, Robert A Wolfe, Tempie E Hulbertshearon, Camille A Jones, Sean Orzol, Philip J HeldAbstract:Abstract HemoDialyzer reuse is commonly practiced in the United States. Recent studies have raised concerns about the mortality risk associated with certain reuse practices. We evaluated adjusted mortality risk during 1- to 2-year follow-up in a representative sample of 12,791 chronic hemodialysis patients treated in 1,394 dialysis facilities from 1994 through 1995. Medical record abstraction provided data on reuse practice, use of bleach, Dialyzer membrane, dialysis dose, and patient characteristics and comorbidity. Mortality risk was analyzed by bootstrapped Cox models by (1) no reuse versus reuse, (2) reuse agent, and (3) Dialyzer membrane with and without the use of bleach, while considering dialysis and patient factors. The relative risk (RR) for mortality did not differ for patients in reuse versus no-reuse units (RR = 0.96; 95% confidence interval [CI], 0.86 to 1.08; P > 0.50), and similar results were found with different levels of adjustment and subgroups (RR = 1.01 to 1.05; 95% CI, lower bound > 0.90, upper bound P > 0.40). The RR for peracetic acid mixture versus formalin varied significantly by membrane type and use of bleach during reprocessing, achieving borderline significance for synthetic membranes. Among synthetic membranes, mortality was greater with low-flux than high-flux membranes (RR = 1.24; 95% CI, 1.02 to 1.52; P = 0.04) and without than with bleach during reprocessing (RR = 1.24; 95% CI, 1.01 to 1.48; P = 0.04). Among all membranes, mortality was lowest for patients treated with high-flux synthetic membranes (RR = 0.82; 95% CI, 0.72 to 0.93; P = 0.002). Although mortality was not greater in reuse than no-reuse units overall, differences may exist in mortality risk by reuse agent. Use of high-flux synthetic membrane Dialyzers was associated with lower mortality risk, particularly when exposed to bleach. Clearance of larger molecules may have a role.
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effects of hemoDialyzer reuse on clearances of urea and β2 microglobulin
Journal of The American Society of Nephrology, 1999Co-Authors: Alfred K Cheung, Lawrence Y Agodoa, John T. Daugirdas, Tom Greene, Nathan W Levin, Thomas A Depner, Frank A Gotch, John K. LeypoldtAbstract:Although Dialyzer reuse in chronic hemodialysis pa- tients is commonly practiced in the United States, performance of reused Dialyzers has not been extensively and critically evaluated. The present study analyzes data extracted from a multicenter clinical trial (the HEMO Study) and examines the effect of reuse on urea and b2-microglobulin (b2M) clearance by low-flux and high-flux Dialyzers reprocessed with various germicides. The Dialyzers evaluated contained either modified cellulosic or polysulfone membranes, whereas the germicides examined included peroxyacetic acid/acetic acid/hydrogen per- oxide combination (Renalin ® ), bleach in conjunction with formaldehyde, glutaraldehyde or Renalin, and heated citric acid. Clearance of b2M decreased, remained unchanged, or increased substantially with reuse, depending on both the membrane material and the reprocessing technique. In contrast, urea clearance decreased only slightly (approximately 1 to 2% per 10 reuses), albeit statistically significantly with reuse, regardless of the porosity of the membrane and reprocessing method. Inasmuch as patient survival in the chronic hemodi- alysis population is influenced by clearances of small solutes and middle molecules, precise knowledge of the membrane material and reprocessing technique is important for the pre- scription of hemodialysis in centers practicing reuse. High-flux hemoDialyzers and reuse of Dialyzers have been widely used for decades, yet the effects of these practices on solute clearances have not been fully evaluated. Although the beneficial effect of increasing urea clearance on clinical outcome has been established, at least up to a single-pool Kt/V value of 1.2 (1), there are also accumulating data suggesting that the removal of middle molecules (using vitamin B12 as marker) influences patient survival (2,3). Thus, maintenance of the clearance of both small and large solutes for reused Dialyzers is important. Reuse can affect Dialyzer performance in at least two different ways. The first is the result of deposition of blood elements inside the lumen of the blood compartment and onto the Dialyzer mem- brane. The second is the result of the reprocessing procedure. At present, the popular germicides used in reprocessing in the United States are Renalin (made up of peroxyacetic acid, acetic acid, and hydrogen peroxide, Minntech, Minneapolis, MN), formaldehyde, and glutaraldehyde (4). To enhance the aesthetic appearance of the Dialyzers during reuse, sodium hypochlorite (bleach) is often used in conjunction with formaldehyde or glutaraldehyde to re- move residual blood proteins. More recently, heated citric acid has also been introduced to clean and disinfect Dialyzers for reuse. Because the chemical composition and mechanical structure are vastly different among various types of dialysis membranes, their interactions with the blood elements and reprocessing agents are likely to differ as well. The HEMO Study is a prospective randomized multicenter trial sponsored by the U.S. National Institutes of Health designed to examine the effects of urea Kt/V and the type of dialysis mem- brane on clinical outcome of chronic hemodialysis patients (5). Various models of Dialyzers and reprocessing methods are used among the 15 clinical centers (more than 45 dialysis units) in the trial. Using this large database, we have prospectively examined the effects of various combinations of Dialyzers and reprocessing agents on the clearance of urea and b2-microglobulin (b2M). The data show that the effects of reuse on b2M are far more drastic than those on urea clearance. Furthermore, the effects vary greatly depending on the dialysis membrane material and reprocessing reagents. These observations confirm and extend our fundamental understanding of alterations in Dialyzer performance during reuse.
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hemoDialyzer mass transfer area coefficients for urea increase at high dialysate flow rates
Kidney International, 1997Co-Authors: John K. Leypoldt, Lawrence Y Agodoa, Prakash Keshaviah, John T. Daugirdas, Tom Greene, Alfred K Cheung, Gerald J BeckAbstract:HemoDialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates. The Dialyzer mass transfer-area coefficient (K o A) for urea is an important determinant of urea removal during hemodialysis and is considered to be constant for a given Dialyzer. We determined urea clearance for 22 different models of commercial hollow fiber Dialyzers ( N = ~5/model, total N=107) in vitro at 37°C for three countercurrent blood (Q b ) and dialysate (Q d ) flow rate combinations. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from urea concentrations in the input and output flows on both the blood and dialysate sides. Urea K o A values, calculated from the mean of the blood and dialysate side clearances, varied between 520 and 1230ml/min depending on the Dialyzer model, but the effect of blood and dialysate flow rate on urea K o A was similar for each. Urea K o A did not change (690 ± 160 vs. 680 ± 140 ml/min, P = NS) when Q b increased from 306 ± 7 to 459 ± 10ml/min at a nominal Q d of 500ml/min. When Q d increased from 504 ± 6 to 819 ± 8ml/min at a nominal Q b of 450ml/min, however, urea K o A increased ( P d from 500 to 800ml/min alters the mass transfer characteristics of hollow fiber hemoDialyzers and results in a larger increase in urea clearance than predicted assuming a constant K o A.