Solute-Solver: A Web-Based Tool for Modeling Urea Kinetics for a Broad Range of Hemodialysis Schedules in Multiple Patients
2009; Elsevier BV; Volume: 54; Issue: 5 Linguagem: Inglês
10.1053/j.ajkd.2009.06.033
ISSN1523-6838
AutoresJohn T. Daugirdas, Thomas A. Depner, Tom Greene, Paul Silisteanu,
Tópico(s)Pharmacological Effects and Toxicity Studies
ResumoPractical application of urea kinetic modeling to measure the delivered dose of hemodialysis is hampered by lack of a reference or gold-standard program that would be widely available and freely distributed. We developed and here describe an open-source JavaScript tool, “Solute-Solver,” capable of batch processing of urea kinetics calculations. The Solute-Solver online interface is available at www.ureakinetics.org; in addition, the tool can be used as a standalone HTML file that is designed to be run using a web browser. Solute-Solver is written in uncompiled JavaScript for transparency and easy modification, and the source code is available for download and modification. The program uses fourth-order Runge-Kutta numerical integration applied to a variable-extracellular-volume 2-pool model to compute a variety of clearance measures, including 1-pool and 2-pool Kt/V, “standard” weekly Kt/V, and other equivalent clearance measures. The program accepts comma- or semicolon-delimited input (which can be produced from a spreadsheet) and generates a separator-delimited output file that can be imported back into a spreadsheet or other database. The program also produces individual patient-by-patient report pages. It typically provides kinetic output for 300 patient treatments in 30-60 seconds. Advantages of this program over previously available equations and algorithms include the capacity to properly model such newer dialysis schedules as 6-times-weekly short daily or nocturnal hemodialysis, as well as account for substantial variation in residual renal function. Ultimately, this effort may promote wider use of formal urea modeling and facilitate research that requires measurement of hemodialysis or hemodialysis adequacy, especially involving the newer expressions of continuous equivalent clearance, and expressions of clearance normalized to body surface area. Practical application of urea kinetic modeling to measure the delivered dose of hemodialysis is hampered by lack of a reference or gold-standard program that would be widely available and freely distributed. We developed and here describe an open-source JavaScript tool, “Solute-Solver,” capable of batch processing of urea kinetics calculations. The Solute-Solver online interface is available at www.ureakinetics.org; in addition, the tool can be used as a standalone HTML file that is designed to be run using a web browser. Solute-Solver is written in uncompiled JavaScript for transparency and easy modification, and the source code is available for download and modification. The program uses fourth-order Runge-Kutta numerical integration applied to a variable-extracellular-volume 2-pool model to compute a variety of clearance measures, including 1-pool and 2-pool Kt/V, “standard” weekly Kt/V, and other equivalent clearance measures. The program accepts comma- or semicolon-delimited input (which can be produced from a spreadsheet) and generates a separator-delimited output file that can be imported back into a spreadsheet or other database. The program also produces individual patient-by-patient report pages. It typically provides kinetic output for 300 patient treatments in 30-60 seconds. Advantages of this program over previously available equations and algorithms include the capacity to properly model such newer dialysis schedules as 6-times-weekly short daily or nocturnal hemodialysis, as well as account for substantial variation in residual renal function. Ultimately, this effort may promote wider use of formal urea modeling and facilitate research that requires measurement of hemodialysis or hemodialysis adequacy, especially involving the newer expressions of continuous equivalent clearance, and expressions of clearance normalized to body surface area. Despite recommendations from standards organizations that favor urea modeling to measure hemodialysis and its adequacy,1Hemodialysis Adequacy 2006 Work GroupClinical practice guidelines for hemodialysis adequacy: Update 2006.Am J Kidney Dis. 2006; 48: S2-S90PubMed Google Scholar, 2Tattersall J. Martin-Malo A. Pedrini L. et al.EBPG guideline on dialysis strategies.Nephrol Dial Transplant. 2007; 22: ii5-ii21Crossref PubMed Scopus (194) Google Scholar a convenient means to rapidly calculate these measures by using urea kinetic analysis is not readily available. The current state-of-the-art model of urea kinetics incorporates 2 serially connected pools of urea distribution with fluid removed from and added to a variable-volume proximal pool representing extracellular water space.3Depner T.A. Prescribing Hemodialysis: A Guide to Urea Modeling. Kluwer Academic Publishers (The Netherlands), 1990Crossref Google Scholar Application of a 2-pool model to calculate a patient's urea volume and generation rate and predict urea concentrations in extracellular and intracellular compartments is not straightforward because it requires iterative numerical and integration methods. The increasing power of personal computers and widespread availability of web-based programming languages allowed us to create a web-based JavaScript tool, “Solute-Solver,” that accomplishes this task. Solute-Solver can be used to assess adequacy for a variety of dialysis treatment schedules, from 2 to 7 times weekly, and can include the contribution of residual renal function up to 15 mL/min. The tool is available at www.ureakinetics.org and can be used directly through the web interface. Because the code is entirely contained in a single HTML-JavaScript file, users who want to run the program on a standalone basis may save the Solute-Solver page as an HTML file and run it using their web browser without the need for internet access. Although the most recent version of the tool will be available at www.ureakinetics.org, the initial release is provided in HTML form as supplementary material (Item S1; available with this article at www.ajkd.org). As an interpretive noncompiled language with transparency that permits easy modification, the JavaScript source code can be adapted to meet local requirements. The 35 input variables and their required formats are listed in Table 1. Although variables can be entered manually in the Solute-Solver interface, the program is configured to receive input data from a comma- or semicolon-delimited file. This facilitates processing of data from multiple patients and transfer to and from any existing patient databases. One method for preparing such a file is to enter the data into a spreadsheet program, taking care that the 35 required fields are in separate columns. The data then can be exported to a separator-delimited file, which is opened in a text editor (such as Windows Notepad or Wordpad) for copying/pasting into Solute-Solver's input textbox. Some examples of input file rows are listed in Box 1. A European-style input and output using semicolons as variable separators and commas as decimal separators is also supported.Table 1Input VariablesColumn No.NameFormatDescription1REPORTy, nIf “y”, will include detailed outputs for each patient on a combined report, 1 patient per page. If “n”, will generate only the separator-delimited spreadsheet file. Suggested input is “y”2ANTHROy, nIf “y”, then will return anthropometric volume and surface area, and age, height, and sex must be included in their respective columns3FAMPUTW0-50 (in %)Weight reduction due to amputation. Enter total from column 2 in KDOQI table⁎From National Kidney Foundation's KDOQI guidelines8; the table is reproduced at ureakinetics.org.4FAMPUTS0-50 (in %)Surface area reduction due to amputation. Enter total from column 3 in KDOQI table⁎From National Kidney Foundation's KDOQI guidelines8; the table is reproduced at ureakinetics.org.5HTUNITSin, cmUnits for height; must be entered even though used only in the calculation of anthropometric volume and surface area6WTUNITSlb, kgUnits for weight; used in the calculation of weight changes during dialysis plus anthropometric volume and surface area7BUNUNITSmg/dL, mmol/LUnits for BUN. PREBUN, POSTBUN, and UUNCONC inputs must be in the same units8PTIDalphanumericPatient identifier9AGE0.1-100 (in y)Patient age; enter “na” unless column 2 set to “y”. Note: Solute-Solver has not been validated in pediatric patients10HEIGHTnumericPatient height using units specified in column 5; enter “na” unless column 2 set to “y”11SEXm, fPatient sex; used only in calculation of anthropometric volume and surface area12LABDATEdd-Mon-yyyy (eg, 02-Jul-2009)Blood-draw date (must be a dialysis day). If entry is made in this column, put “na” in column 13. The program will calculate LABDAYOFWK internally from the blood-draw date13LABDAYOFWK1-7 for Mon-SunBlood-draw day of week; must be 1 of the dialysis days in column 14. If LABDAYOFWK is entered, put “na” in column 1214SCHEDULEeg, 1347 for MonWedThuSatDialysis schedule; 1 = Mon. Minimum is 2 d/wk; maximum is 7 d/wk. For alternate-day schedule, input “qod” (in which case column 13 should be 2 or 3)15KRUPS0-15 (in mL/min), 999Residual urea clearance (blood water). Alternatively, enter 999 if you wish the program to compute Kru from urine urea concentration, urine volume, and collection time and then enter these values in columns 26-2916PREBUNnumericPredialysis BUN, using units specified in column 717POSTBUNnumericPostdialysis BUN, using units specified in column 7; program assumes specimen drawn 15 s postdialysis using a slow-flow technique18QBnumeric (in mL/min)Blood flow rate. This program assumes that the entered value is the delivered blood flow rate and does not downregulate this input value19QDnumeric (in mL/min)Dialysate flow rate. Online hemodiafiltration rates entered in columns 30 and 31 will be subtracted from this QD value. If infusing replacement fluid, augment QD here by the infusion rate. For pure hemofiltration, set QD to 020TDDnumeric (in min)Treatment time; program assumes the same duration of dialysis for each treatment during the week21PREWEIGHTnumericPredialysis weight, using units specified in column 622POSTWEIGHTnumericPostdialysis weight, using units specified in column 623ACCESSa, v, uArterial, venous, or unknown. Currently, Solute-Solver treats all accesses identically24KOAnumeric (in mL/min)K0A is the dialyzer mass transfer area coefficient; use the manufacturer-specified value. The program will downgrade this to an in vivo K0A estimate25DZERNAMEalphanumericDialyzer brand name/model. This information is not used but is simply passed through to the output separator-delimited file and report page26UUNCONCnumericUrea nitrogen concentration (in units set in column 7) in the collected urine sample. Set to “na” if Kru computation is not desired27UVOLnumeric (in mL)Volume of collected urine sample. Set to “na” if Kru computation is not desired28UDURnumeric (in min)Duration of urine collection period; range, 360-4, 320. Set to “na” if Kru computation is not desired29TIMETOPREnumeric (in min)Time between end of urine collection period and start of dialysis in which the predialysis blood was drawn. The program is set up only for situations in which urine was collected before the dialysis during which the pre- and post-BUN were drawn; this usually will be < 1,440 min30HDFPREDILnumeric (in mL/min)Hemodiafiltration predilution infusion rate. Set to 0 if hemodiafiltration not done31HDFPOSTDILnumeric (in mL/min)Hemodiafiltration postdilution infusion rate. Set to 0 if hemodiafiltration not done32MODE996,997,998,999Special input mode to overide use of K0A (column 24); if not applicable, enter “na”. Code 996 is Kt + V input mode; enter Kt in column 33, V in column 34, and “na” in POSTBUN (column 17). Code 997 is Kt mode; enter Kt in column 33. Code 998 is V mode; enter V in column 33. Code 999 is Kd mode; enter Kd (the total clearance for the blood-draw day) in column 3333OCMKT-V-KDnumericEntry field for parameters related to MODE (column 32). If column 32 is “996” or “997”, enter Kt (in L). If column 32 is “998”, enter V (in L). If column 32 is “999”, enter Kd (in mL/min). If column 32 is “na”, enter “na”34EXTRA1numeric (in L), alphanumericIf column 32 is set to “996” mode, enter V (in L). Otherwise, this space is for any extra label (eg, group or location number) describing the patient or treatment and is not used by the program, but it is passed through to the separator-delimited output and treatment report. Enter “extra1” if not used35EXTRA2alphanumericThis space is for any extra label (eg, group or location number) describing the patient or treatment and is not used by the program, but it is passed through to the separator-delimited output and treatment report. Enter “extra2” if not usedNote: Input data must be a file 35 columns in width.Abbreviations and definitions: BUN, blood urea nitrogen; Kd, dialyzer clearance; KDOQI, Kidney Disease Outcomes Quality Initiative; Kru, residual renal clearance; Kt, clearance multiplied by dialysis time; K0A, dialyzer mass transfer coefficient; V, volume. From National Kidney Foundation's KDOQI guidelines8National Kidney FoundationK/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy: Update 2000.Am J Kidney Dis. 2001; 37: S65-S136PubMed Google Scholar; the table is reproduced at ureakinetics.org. Open table in a new tab Box 1Sample Input DataTabled 1Parameters Prespecified Kru (col 15=4.5) No anthropometrics (col 2=n) Lab day = Wednesday (col 12=na, col 13=3) Schedule = MWF (col 14=135)Input row y,n,0,0,in,kg,mg/dL,Joe,na,na,m,na,3,135,4.5,80,30,400,500,180,73,70,a,800,dzername,na,na,na,na,0,0,na,na,extra1,extra2Parameters Prespecified Kru (col 15=4.5) With anthropometrics (col 2=y; cols 9,10,11=30 [age], 72 [height in inches], f [sex]) Lab calendar date = Dec 2, 2009 (col 12=02-Dec-2009; col 13=na)Input row y,y,0,0,in,kg,mg/dL,Mary,30,72,f,02-Dec-2009,na,246,4.5,80,20,400,500,240,80,78,a,800,dzername,na,na,na,na, 0,0,na,na,extra1,extra2Parameters Kru from urine collection (col 15=999; cols 26-29 filled in) No anthropometricsInput row y,n,0,0,in,kg,mg/dL,John,na,na,m,na,3,135,999,80,30,400,500,180,73,70,a,800,dzername,500,500,1440,60,0,0,na,na,extra1,extra2Parameters Kd input mode (col 32=999; col 33=256 [Kd]) No anthropometricsInput row y,n,0,0,in,kg,mg/dL,Fred,na,na,m,na,3,135,3,80,30,400,500,180,73,70,a,800,dzername,na,na,na,na,0,0,999,256,extra1,extra2Parameters V input mode (col 32=998; col 33=35 [V in L]) No anthropometricsInput row y,n,0,0,in,kg,mg/dL,Fred,na,na,m,na,3,135,3,80,30,400,500,180,73,70,a,800,dzername,na,na,na,na,0,0,998,35,extra1,extra2Note: For each item mentioned in the parameters sections, the respective column entry is shown in bold.Abbreviations and definitions: col, column; Kd, total dialyzer clearance; Kru, residual urea clearance; V, estimated postdialysis 2-pool volume, which should be entered in liters. Open table in a new tab Note: Input data must be a file 35 columns in width. Abbreviations and definitions: BUN, blood urea nitrogen; Kd, dialyzer clearance; KDOQI, Kidney Disease Outcomes Quality Initiative; Kru, residual renal clearance; Kt, clearance multiplied by dialysis time; K0A, dialyzer mass transfer coefficient; V, volume. Tabled 1Parameters Prespecified Kru (col 15=4.5) No anthropometrics (col 2=n) Lab day = Wednesday (col 12=na, col 13=3) Schedule = MWF (col 14=135)Input row y,n,0,0,in,kg,mg/dL,Joe,na,na,m,na,3,135,4.5,80,30,400,500,180,73,70,a,800,dzername,na,na,na,na,0,0,na,na,extra1,extra2Parameters Prespecified Kru (col 15=4.5) With anthropometrics (col 2=y; cols 9,10,11=30 [age], 72 [height in inches], f [sex]) Lab calendar date = Dec 2, 2009 (col 12=02-Dec-2009; col 13=na)Input row y,y,0,0,in,kg,mg/dL,Mary,30,72,f,02-Dec-2009,na,246,4.5,80,20,400,500,240,80,78,a,800,dzername,na,na,na,na, 0,0,na,na,extra1,extra2Parameters Kru from urine collection (col 15=999; cols 26-29 filled in) No anthropometricsInput row y,n,0,0,in,kg,mg/dL,John,na,na,m,na,3,135,999,80,30,400,500,180,73,70,a,800,dzername,500,500,1440,60,0,0,na,na,extra1,extra2Parameters Kd input mode (col 32=999; col 33=256 [Kd]) No anthropometricsInput row y,n,0,0,in,kg,mg/dL,Fred,na,na,m,na,3,135,3,80,30,400,500,180,73,70,a,800,dzername,na,na,na,na,0,0,999,256,extra1,extra2Parameters V input mode (col 32=998; col 33=35 [V in L]) No anthropometricsInput row y,n,0,0,in,kg,mg/dL,Fred,na,na,m,na,3,135,3,80,30,400,500,180,73,70,a,800,dzername,na,na,na,na,0,0,998,35,extra1,extra2Note: For each item mentioned in the parameters sections, the respective column entry is shown in bold.Abbreviations and definitions: col, column; Kd, total dialyzer clearance; Kru, residual urea clearance; V, estimated postdialysis 2-pool volume, which should be entered in liters. Open table in a new tab Note: For each item mentioned in the parameters sections, the respective column entry is shown in bold. Abbreviations and definitions: col, column; Kd, total dialyzer clearance; Kru, residual urea clearance; V, estimated postdialysis 2-pool volume, which should be entered in liters. Required input variables are pre- and postdialysis weights and blood urea nitrogen (BUN) values, the components required to estimate dialyzer clearance (K0A [dialyzer mass transfer area coefficient], Qb [blood flow rate], and Qd [dialysate flow rate]), treatment time (Td), and the dialysis schedule. Weight (and height; for optional anthropometric variables, discussed later) may be entered in English or metric units. BUN may be entered in either mg/dL or mmol/L; user-provided BUN values are converted to plasma water values by dividing by 0.93 (plasma is assumed to contain 93% water), then converted to mg/mL. The day on which the pre- and postdialysis BUN measurements are made can be specified as either a day of the week (1 to 7) or a calendar date. In either case, the alternative entry should be listed as “na.” The weekday for the modeled dialysis session is set as the initial day of the weekly urea nitrogen profile to be generated by the program. If dialyzer clearance is known, it may be entered directly, overriding its computation from the dialyzer K0A and blood and dialysate flow rates (Box 1). Another option is to enter the estimated urea distribution volume (V) in liters and let the program compute the estimated dialyzer clearance from the predialysis and postdialysis BUN values (Box 1). Residual urea clearance can either be entered as a known variable or calculated from the urine urea nitrogen concentration, urine volume, and timing of a collected urine sample (Box 1). Additional anthropometric variables (sex, height, and age) are optional, but when provided, are used to compute anthropometric V using the Watson equation4Watson P.E. Watson I.D. Batt R.D. Total body water volumes for adult males and females estimated from simple anthropometric measurements.Am J Clin Nutr. 1980; 33: 27-39PubMed Google Scholar if patient age is 14 years or older or the Mellits and Cheek equation5Mellits E.D. Cheek D.B. The assessment of body water and fatness from infancy to adulthood.Monographs Soc Res Child Dev Ser 140. 1970; 35: 12-26Crossref PubMed Scopus (137) Google Scholar if age is younger than 14 years. Height and weight also are used to compute body surface area by using the Dubois equation6Dubois D. Dubois E.F. A formula to estimate the approximate surface area if height and weight be known.Arch Intern Med. 1916; 17: 863-871Crossref Scopus (4100) Google Scholar if 14 years or older or the Gehan and George7Gehan E. George S.L. Estimation of human body surface area from height and weight.Cancer Chemother Rep. 1970; 54: 225-235PubMed Google Scholar equation if younger than 14 years. The effects of amputations on V and surface area are computed according to the method recommended in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) peritoneal adequacy guidelines from 2000.8National Kidney FoundationK/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy: Update 2000.Am J Kidney Dis. 2001; 37: S65-S136PubMed Google Scholar Briefly, the total number of limbs amputated is translated into an estimated weight reduction as read from a table (Table II-4 in reference8National Kidney FoundationK/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy: Update 2000.Am J Kidney Dis. 2001; 37: S65-S136PubMed Google Scholar). This then is used to compute estimated body weight in the absence of these amputations. Either the Watson or the Mellits-Cheek equation is used to compute the estimated value for V in the absence of amputations, and this value then is decreased by the percentage of effect of the total amputations. For body surface area adjustment, calculations proceed in a similar fashion, except a different set of percentages (from Table II-4, page S123 in reference8National Kidney FoundationK/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy: Update 2000.Am J Kidney Dis. 2001; 37: S65-S136PubMed Google Scholar) are used to decrease the nonamputated body surface estimate. There are 2 pass-through variables (EXTRA1 and 2), alphanumeric in nature, that are not used by the program (except in one of the special input modes) but simply are linked to the treatment and passed through to the output. Users may place within these fields any desired information that is connected to the treatment. The urea modeling approach used in this program is similar to that used to analyze data from the National Institutes of Health Hemodialysis (HEMO) clinical study9Daugirdas J.T. Depner T.A. Gotch F.A. et al.Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study.Kidney Int. 1997; 52: 1395-1405Crossref PubMed Scopus (160) Google Scholar, 10Daugirdas J.T. Greene T. Depner T.A. et al.; Hemodialysis Study Group: Factors that affect postdialysis rebound in serum urea concentration, including the rate of dialysis: Results from the HEMO Study.J Am Soc Nephrol. 2004; 15: 194-203Crossref PubMed Scopus (64) Google Scholar and that is currently used to analyze solute clearances in the Frequent Hemodialysis Network (FHN) trials of daytime and nocturnal dialysis delivered 6 times weekly.11Greene T. Daugirdas J.T. Depner T.A. et al.; Frequent Hemodialysis Network Study Group, National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health: Solute clearances and fluid removal in the frequent hemodialysis network trials.Am J Kidney Dis. 2009; 53: 835-844Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar The equations used for the 1- and 2-pool models, both of which allow a variable volume, are modified from several sources.3Depner T.A. Prescribing Hemodialysis: A Guide to Urea Modeling. Kluwer Academic Publishers (The Netherlands), 1990Crossref Google Scholar, 9Daugirdas J.T. Depner T.A. Gotch F.A. et al.Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study.Kidney Int. 1997; 52: 1395-1405Crossref PubMed Scopus (160) Google Scholar, 10Daugirdas J.T. Greene T. Depner T.A. et al.; Hemodialysis Study Group: Factors that affect postdialysis rebound in serum urea concentration, including the rate of dialysis: Results from the HEMO Study.J Am Soc Nephrol. 2004; 15: 194-203Crossref PubMed Scopus (64) Google Scholar Urea generation rate (G) is calculated by using a previously described iterative method12Depner T.A. Cheer A. Modeling urea kinetics with two vs. three BUN measurements A critical comparison.ASAIO Trans. 1989; 35: 499-502Crossref PubMed Google Scholar that systematically adjusts G while cycling until the modeled predialysis BUN matches the measured value. Dialyzer clearance is resolved in 1 of 3 ways. In default mode, diffusive dialyzer clearance (Kdif) is calculated from the dialyzer K0A and countercurrent flow rates of dialysate and blood (Qb and Qd), assuming an exponential change in concentrations across the dialyzer from inflow to outflow port.3Depner T.A. Prescribing Hemodialysis: A Guide to Urea Modeling. Kluwer Academic Publishers (The Netherlands), 1990Crossref Google Scholar In dialyzer clearance (Kd) input mode, the estimated dialyzer clearance is entered directly. In V input mode, the estimated urea distribution volume is entered and Kd is estimated by using urea kinetic equations modified from a method described by Casino et al,13Casino F.G. Basile C. Gaudiano V. Lopez T. A modified algorithm of the single pool urea kinetic model.Nephrol Dial Transplant. 1990; 5: 214-219Crossref PubMed Scopus (28) Google Scholar the details of which are beyond the scope of the present report. The dialysis-machine-reported conductivity-based clearance (K) multiplied by time (t), or Kt, can also be entered, from which the program also can compute Kd. In default mode, the first step is to adjust the user-supplied K0A published by the dialyzer manufacturer. K0A values supplied by the dialyzer manufacturer most often are derived from in vitro measurements of solute removal from saline solutions; thus, the program adjusts these downward to more realistic in vivo values.14Depner T.A. Greene T. Daugirdas J.T. Cheung A.K. Gotch F.A. Leypoldt J.K. Dialyzer performance in the HEMO Study: In vivo K0A and true blood flow determined from a model of cross-dialyzer urea extraction.ASAIO J. 2004; 50: 85-93Crossref PubMed Scopus (38) Google Scholar The equation used to estimate in vivo K0A from the industry-supplied value (equation 1; all numbered equations are provided in the Appendix) was designed to be consistent with simultaneous inlet-outlet measurements of dialyzer clearance during the HEMO Study.14Depner T.A. Greene T. Daugirdas J.T. Cheung A.K. Gotch F.A. Leypoldt J.K. Dialyzer performance in the HEMO Study: In vivo K0A and true blood flow determined from a model of cross-dialyzer urea extraction.ASAIO J. 2004; 50: 85-93Crossref PubMed Scopus (38) Google Scholar The program also adjusts the dialyzer K0A as a function of the dialysate flow rate. At greater dialysate flow rates, better permeation of dialysate into the fiber bundle effectively increases the dialyzer surface area and K0A.14Depner T.A. Greene T. Daugirdas J.T. Cheung A.K. Gotch F.A. Leypoldt J.K. Dialyzer performance in the HEMO Study: In vivo K0A and true blood flow determined from a model of cross-dialyzer urea extraction.ASAIO J. 2004; 50: 85-93Crossref PubMed Scopus (38) Google Scholar, 15Leypoldt J.K. Cheung A.K. Agodoa L.Y. Daugirdas J.T. Greene T. Keshaviah P.R. Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates The Hemodialysis (HEMO) Study.Kidney Int. 1997; 51: 2013-2017Crossref PubMed Scopus (124) Google Scholar Low dialysate flow rates (<500 mL/min) have the opposite effect, which may significantly decrease K0A (even to levels below those calculated by the presently used equation).16Ouseph R. Ward R.A. Increasing dialysate flow rate increases dialyzer urea mass transfer-area coefficients during clinical use.Am J Kidney Dis. 2001; 37: 316-320Abstract Full Text PDF PubMed Scopus (63) Google Scholar, 17Leypoldt J.K. Cheung A.K. Effect of low dialysate flow rate on hemodialyzer mass transfer area coefficients for urea and creatinine.Home Hemodial Int. 1999; 3: 51-54Google Scholar The diffusive dialyzer clearance (Kdif) then is determined from the estimated in vivo K0A value, Qb, and Qd according to equation 2.3Depner T.A. Prescribing Hemodialysis: A Guide to Urea Modeling. Kluwer Academic Publishers (The Netherlands), 1990Crossref Google Scholar Reduction from whole blood to blood water clearance in the clearance equation uses a multiplier of 0.86 for blood water content. This is a weighted average of the presumed urea distribution space in erythrocytes (0.72) and plasma (0.93), assuming hematocrit of 0.33.3Depner T.A. Prescribing Hemodialysis: A Guide to Urea Modeling. Kluwer Academic Publishers (The Netherlands), 1990Crossref Google Scholar Kdif calculated in this manner then is adjusted for the expected fluid removal rate during each dialysis session by using equation 3.3Depner T.A. Prescribing Hemodialysis: A Guide to Urea Modeling. Kluwer Academic Publishers (The Netherlands), 1990Crossref Google Scholar The resulting clearance is a total dialyzer clearance (Kd) that includes the ultrafiltration component. When hemodiafiltration is used, the program computes the additional clearance of urea due to this process based on the predilution and/or postdilution replacement fluid infusion rate.18Ficheux A. Argilés A. Mion H. Mion C.M. Influence of convection on small molecule clearances in online hemodiafiltration.Kidney Int. 2000; 57: 1755-1763PubMed Scopus (0) Google Scholar Assumptions are made that fluid accumulation occurs at a constant rate during the week excluding dialysis sessions, and fluid removal during each dialysis session is adjusted by dialysis staff to achieve the same postdialysis weight. The duration of each dialysis treatment during the week is assumed to be identical; therefore, sessions after longer interdialysis intervals require a greater rate of ultrafiltration. This results in a slightly greater Kd for sessions that follow longer interdialysis intervals. Single-pool (1p) analysis is not strictly required, but is computed by the program for comparison purposes and to meet regulatory requirements and because single-pool analysis yields values for modeled urea distribution volume (V1p) and generation rate (G1p) that subsequently can be adjusted to estimated 2-pool values that are close to the final values, allowing for fewer iterations in the 2-pool (2p) portion of the program that requires numerical analysis for integration (discussed later). The variable volume single-pool equations described by Gotch are used.3Depner T.A. Prescribing Hemodialysis: A Guide to Urea Modeling. Kluwer Acade
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