Kt/V and the adequacy of hemodialysis


A central issue in the management of patients undergoing maintenance hemodialysis is the assessment of adequacy of dialysis. Simply following the blood urea nitrogen (BUN) is insufficient because a low BUN can reflect inadequate nutrition rather than sufficient dialytic urea removal. Monitoring the patient's symptoms alone is also insufficient, since the combination of dialysis plus erythropoietin to correct anemia can eliminate most uremic symptoms although the patient may be underdialyzed. (See "Erythropoietin for the anemia of chronic kidney disease among predialysis and peritoneal dialysis patients" and "Erythropoietin for the anemia of chronic kidney disease in hemodialysis patients".) Thus, in addition to symptoms, patient nutrition and survival appear to best reflect dialysis adequacy.


The National Cooperative Dialysis Study (NCDS) established that the timed average urea concentration and the protein catabolic rate (PCR) were important determinants of morbidity and mortality in hemodialysis patients [1,2]. (See "Protein catabolic rate in maintenance dialysis".) In particular, well-nourished patients with a more intensive dialysis prescription and a lower timed average BUN had a better outcome. In a patient with little or no urine output, the PCR (in g/day) is equal to the sum of the dialysis and stool losses of urea, protein, and amino acids. These losses (the PCR) are roughly equal to protein intake when a patient is in a steady state with a relatively constant predialysis BUN.

Gotch later used a mechanistic analysis of these data and showed that the Kt/V of urea (see below) was an important measure of clinical outcome [3]. Urea was chosen by the NCDS as the clearance marker for the Kt/V since it is a reflection both of dietary protein intake and of the efficiency of removal of small uremic toxins. (See "Uremic toxins".)

Individualizing the hemodialysis prescription to a particular patient's needs using Kt/V can be a useful tool in providing a safe and cost-effective dialysis treatment. This can be accomplished with urea kinetic modeling, which allows for variations in dialysis time, use of larger, high efficiency, high-flux dialyzers, and optimization of dietary protein need. Urea kinetic modeling is a method for verifying that the amount of dialysis prescribed (the prescribed Kt/V) equals the amount of dialysis delivered (the effective Kt/V). Kinetic modeling also quantifies the amount of urea generated, which is a marker of the protein catabolic rate and therefore of protein intake.


Kt/V is defined as the dialyzer clearance of urea (K, obtained from the manufacturer in mL/min, and periodically measured and verified by the dialysis team) multiplied by the duration of the dialysis treatment (t, in minutes) divided by the volume of distribution of urea in the body (V, in mL), which is approximately equal to the total body water. The correction of total urea removal (Kt) for volume of distribution is important because, in a large patient, a given degree of urea loss represents a lower rate of removal of the total body burden of urea (and presumably of other small uremic toxins).


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2014. | This topic last updated: Nov 2, 2012.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
  1. Lowrie EG, Laird NM, Parker TF, Sargent JA. Effect of the hemodialysis prescription of patient morbidity: report from the National Cooperative Dialysis Study. N Engl J Med 1981; 305:1176.
  2. Harter HR. Review of significant findings from the National Cooperative Dialysis Study and recommendations. Kidney Int Suppl 1983; :S107.
  3. Gotch FA, Sargent JA. A mechanistic analysis of the National Cooperative Dialysis Study (NCDS). Kidney Int 1985; 28:526.
  4. Hemodialysis Adequacy 2006 Work Group. Clinical practice guidelines for hemodialysis adequacy, update 2006. Am J Kidney Dis 2006; 48 Suppl 1:S2.
  5. Eknoyan, G, Levey, AS, Beck, GJ, et al. The hemodialysis (HEMO) study: rationale for selection of interventions. Semin Dial 1996; 9:24.
  6. Daugirdas JT. Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol 1993; 4:1205.
  7. Daugirdas JT, Depner TA. A nomogram approach to hemodialysis urea modeling. Am J Kidney Dis 1994; 23:33.
  8. Goldstein SL, Sorof JM, Brewer ED. Natural logarithmic estimates of Kt/V in the pediatric hemodialysis population. Am J Kidney Dis 1999; 33:518.
  9. Daugirdas JT. Rapid methods of estimating Kt/V: three formulas compared. ASAIO Trans 1990; 36:M362.
  10. Lowrie EG, Lew NL. The urea reduction ratio (URR). A simple method for evaluating hemodialysis treatment. Contemp Dial Nephrol 1992; 12:11.
  11. Frankenfield DL, McClellan WM, Helgerson SD, et al. Relationship between urea reduction ratio, demographic characteristics, and body weight for patients in the 1996 National ESRD Core Indicators Project. Am J Kidney Dis 1999; 33:584.
  12. Daugirdas JT. Linear estimates of variable-volume, single-pool Kt/V: an analysis of error. Am J Kidney Dis 1993; 22:267.
  13. Sherman RA, Cody RP, Rogers ME, Solanchick JC. Accuracy of the urea reduction ratio in predicting dialysis delivery. Kidney Int 1995; 47:319.
  14. Covic A, Goldsmith DJ, Hill K, et al. Urea kinetic modelling--are any of the 'bedside' Kt/V formulae reliable enough? Nephrol Dial Transplant 1998; 13:3138.
  15. Cheng YL, Choi KS, Chau KF, et al. Urea reduction ratio that considers effects of ultrafiltration and intradialytic urea generation. Am J Kidney Dis 2001; 37:544.
  16. Traynor JP, Oun HA, McKenzie P, et al. Assessing the utility of the stop dialysate flow method in patients receiving haemodiafiltration. Nephrol Dial Transplant 2005; 20:2479.
  17. Kerr PG, Argilés A, Canaud B, et al. Accuracy of Kt/V estimations in high-flux haemodiafiltration using per cent reduction of urea: incorporation of urea rebound. Nephrol Dial Transplant 1993; 8:149.
  18. Pflederer BR, Torrey C, Priester-Coary A, et al. Estimating equilibrated Kt/V from an intradialytic sample: effects of access and cardiopulmonary recirculations. Kidney Int 1995; 48:832.
  19. Castro MC, Romão JE Jr, Marcondes M. Measurement of blood urea concentration during haemodialysis is not an accurate method to determine equilibrated post-dialysis urea concentration. Nephrol Dial Transplant 2001; 16:1814.
  20. Traynor JP, Geddes CC, Ferguson C, Mactier RA. Predicting 30-minute postdialysis blood urea concentrations using the stop dialysate flow method. Am J Kidney Dis 2002; 39:308.
  21. Owen WF Jr, Meyer KB, Schmidt G, Alfred H. Methodological limitations of the ESRD Core Indicators Project: an ESRD network's experience with implementing an ESRD quality survey. Medical Review Board of the ESRD Network of New England. Am J Kidney Dis 1997; 30:349.
  22. European Best Practice Guidelines Expert Group on Hemodialysis, European Renal Association. Section II. Haemodialysis adequacy. Nephrol Dial Transplant 2002; 17 Suppl 7:16.
  23. Jindal K, Chan CT, Deziel C, et al. Hemodialysis clinical practice guidelines for the Canadian Society of Nephrology. J Am Soc Nephrol 2006; 17:S1.
  24. Owen WF Jr, Lew NL, Liu Y, et al. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. N Engl J Med 1993; 329:1001.
  25. Delmez JA, Windus DW. Hemodialysis prescription and delivery in a metropolitan community. The St. Louis Nephrology Study Group. Kidney Int 1992; 41:1023.
  26. Morbidity and mortality of renal dialysis: an NIH consensus conference statement. Consensus Development Conference Panel. Ann Intern Med 1994; 121:62.
  27. Held PJ, Port FK, Wolfe RA, et al. The dose of hemodialysis and patient mortality. Kidney Int 1996; 50:550.
  28. Dumler F, Stalla K, Mohini R, et al. Clinical experience with short-time hemodialysis. Am J Kidney Dis 1992; 19:49.
  29. United States Renal Data System. Excerpts from the USRDS 2000 annual data report: Atlas of end-stage renal disease in the United States. Am J Kidney Dis 2000; 36(Suppl 2):S127.
  30. 2007 Annual Report: ESRD clinical performance measures project. Am J Kidney Dis Suppl 2008; 51(Suppl 1):S1.
  31. United States Renal Data System. Excerpts from the USRDS 2006 annual data report: Atlas of end-stage renal disease in the United States. Am J Kidney Dis 2007; 49(Suppl 1):S1.
  32. Hecking E, Bragg-Gresham JL, Rayner HC, et al. Haemodialysis prescription, adherence and nutritional indicators in five European countries: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2004; 19:100.
  33. Leonard MB, Stablein DM, Ho M, et al. Racial and center differences in hemodialysis adequacy in children treated at pediatric centers: a North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) report. J Am Soc Nephrol 2004; 15:2923.
  34. Chand DH, Brier M, Strife CF. Comparison of vascular access type in pediatric hemodialysis patients with respect to urea clearance, anemia management, and serum albumin concentration. Am J Kidney Dis 2005; 45:303.
  35. Gorman G, Furth S, Hwang W, et al. Clinical outcomes and dialysis adequacy in adolescent hemodialysis patients. Am J Kidney Dis 2006; 47:285.
  36. Eknoyan G, Beck GJ, Cheung AK, et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002; 347:2010.
  37. Depner T, Daugirdas J, Greene T, et al. Dialysis dose and the effect of gender and body size on outcome in the HEMO Study. Kidney Int 2004; 65:1386.
  38. Port FK, Wolfe RA, Hulbert-Shearon TE, et al. High dialysis dose is associated with lower mortality among women but not among men. Am J Kidney Dis 2004; 43:1014.
  39. Allon M, Depner TA, Radeva M, et al. Impact of dialysis dose and membrane on infection-related hospitalization and death: results of the HEMO Study. J Am Soc Nephrol 2003; 14:1863.
  40. Unruh M, Benz R, Greene T, et al. Effects of hemodialysis dose and membrane flux on health-related quality of life in the HEMO Study. Kidney Int 2004; 66:355.
  41. Cheung AK, Rocco MV, Yan G, et al. Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study. J Am Soc Nephrol 2006; 17:546.
  42. Cheung AK, Greene T, Leypoldt JK, et al. Association between serum 2-microglobulin level and infectious mortality in hemodialysis patients. Clin J Am Soc Nephrol 2008; 3:69.
  43. Winchester JF, Salsberg JA, Levin NW. Beta-2 microglobulin in ESRD: an in-depth review. Adv Ren Replace Ther 2003; 10:279.
  44. Locatelli F. Dose of dialysis, convection and haemodialysis patients outcome--what the HEMO study doesn't tell us: the European viewpoint. Nephrol Dial Transplant 2003; 18:1061.
  45. Rocco MV, Cheung AK, Greene T, et al. The HEMO Study: applicability and generalizability. Nephrol Dial Transplant 2005; 20:278.
  46. Greene T, Daugirdas J, Depner T, et al. Association of achieved dialysis dose with mortality in the hemodialysis study: an example of "dose-targeting bias". J Am Soc Nephrol 2005; 16:3371.
  47. Shemin D, Bostom AG, Laliberty P, Dworkin LD. Residual renal function and mortality risk in hemodialysis patients. Am J Kidney Dis 2001; 38:85.
  48. Termorshuizen F, Dekker FW, van Manen JG, et al. Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol 2004; 15:1061.
  49. Vilar E, Wellsted D, Chandna SM, et al. Residual renal function improves outcome in incremental haemodialysis despite reduced dialysis dose. Nephrol Dial Transplant 2009; 24:2502.
  50. Shafi T, Jaar BG, Plantinga LC, et al. Association of residual urine output with mortality, quality of life, and inflammation in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. Am J Kidney Dis 2010; 56:348.
  51. Tattersall J, Martin-Malo A, Pedrini L, et al. European best practice guidelines on haemodialysis. Nephrol Dial Transplant 2007; 22 (Suppl 2):ii1.
  52. Blake PG. Adequacy of dialysis revisited. Kidney Int 2003; 63:1587.
  53. Kloppenburg WD, Stegeman CA, Hooyschuur M, et al. Assessing dialysis adequacy and dietary intake in the individual hemodialysis patient. Kidney Int 1999; 55:1961.
  54. Coyne DW, Delmez J, Spence G, Windus DW. Impaired delivery of hemodialysis prescriptions: an analysis of causes and an approach to evaluation. J Am Soc Nephrol 1997; 8:1315.
  55. Ifudu O, Mayers JD, Matthew JJ, et al. Standardized hemodialysis prescriptions promote inadequate treatment in patients with large body mass. Ann Intern Med 1998; 128:451.
  56. Powers KM, Wilkowski MJ, Helmandollar AW, et al. Improved urea reduction ratio and Kt/V in large hemodialysis patients using two dialyzers in parallel. Am J Kidney Dis 2000; 35:266.
  57. Hauk M, Kuhlmann MK, Riegel W, Köhler H. In vivo effects of dialysate flow rate on Kt/V in maintenance hemodialysis patients. Am J Kidney Dis 2000; 35:105.
  58. Mehta HK, Deabreu D, McDougall JG, Goldstein MB. Correction of discrepancy between prescribed and actual blood flow rates in chronic hemodialysis patients with use of larger gauge needles. Am J Kidney Dis 2002; 39:1231.
  59. Lambie SH, Taal MW, Fluck RJ, McIntyre CW. Analysis of factors associated with variability in haemodialysis adequacy. Nephrol Dial Transplant 2004; 19:406.
  60. Ahmed J, Besarab A, Lubkowski T, Frinak S. Effect of differing blood lines on delivered blood flow during hemodialysis. Am J Kidney Dis 2004; 44:498.
  61. Sehgal AR, Leon JB, Siminoff LA, et al. Improving the quality of hemodialysis treatment: a community-based randomized controlled trial to overcome patient-specific barriers. JAMA 2002; 287:1961.
  62. Stoffel MP, Barth C, Lauterbach KW, Baldamus CA. Evidence-based medical quality management in dialysis--Part I: Routine implementation of QiN, a German quality management system. Clin Nephrol 2004; 62:208.
  63. Stoffel MP, Barth C, Lauterbach KW, Baldamus CA. Evidence-based medical quality management in dialysis--Part II: Improvement of hemodialysis adequacy. Clin Nephrol 2004; 62:219.
  64. I. NKF-K/DOQI Clinical Practice Guidelines for Hemodialysis Adequacy: update 2000. Am J Kidney Dis 2001; 37:S7.
  65. Schulman G, Delmez J, Greene T, et al. Experience with two dialyzers in series in the HEMO study (abstract). J Am Soc Nephrol 2000; 11:177A.
  66. Splendiani G, Zazzaro D, Tullio T, et al. Bidialysis: a new technique. Int J Artif Organs 2001; 24:70.
  67. Fritz BA, Doss S, McCann LM, Wrone EM. A comparison of dual dialyzers in parallel and series to improve urea clearance in large hemodialysis patients. Am J Kidney Dis 2003; 41:1008.
  68. Kooistra MP, Vos J, Koomans HA, Vos PF. Daily home haemodialysis in The Netherlands: effects on metabolic control, haemodynamics, and quality of life. Nephrol Dial Transplant 1998; 13:2853.
  69. Keshaviah P. The solute removal index--a unified basis for comparing disparate therapies. Perit Dial Int 1995; 15:101.
  70. Cheng YL, Shek CC, Wong FK, et al. Determination of the solute removal index for urea by using a partial spent dialysate collection method. Am J Kidney Dis 1998; 31:986.
  71. Depner TA, Greene T, Gotch FA, et al. Imprecision of the hemodialysis dose when measured directly from urea removal. Hemodialysis Study Group. Kidney Int 1999; 55:635.
  72. Marshall MR, Santamaria P, Collins JF. Biostat 1000 and Daugirdas blood-based hemodialysis quantification: agreement and reproducibility. Am J Kidney Dis 1998; 31:1011.
  73. Owen WF Jr, Chertow GM, Lazarus JM, Lowrie EG. Dose of hemodialysis and survival: differences by race and sex. JAMA 1998; 280:1764.
  74. McClellan WM, Soucie JM, Flanders WD. Mortality in end-stage renal disease is associated with facility-to-facility differences in adequacy of hemodialysis. J Am Soc Nephrol 1998; 9:1940.
  75. Chertow GM, Owen WF, Lazarus JM, et al. Exploring the reverse J-shaped curve between urea reduction ratio and mortality. Kidney Int 1999; 56:1872.
  76. Wolfe RA, Ashby VB, Daugirdas JT, et al. Body size, dose of hemodialysis, and mortality. Am J Kidney Dis 2000; 35:80.
  77. Lowrie EG, Chertow GM, Lew NL, et al. The urea [clearance x dialysis time] product (Kt) as an outcome-based measure of hemodialysis dose. Kidney Int 1999; 56:729.
  78. Lowrie, EG, Lew, NL. The urea reduction ratio (URR): A simple method for evaluating hemodialysis treatment. Contemp Dial Nephrol 1991; (Feb):11.
  79. Li Z, Lew NL, Lazarus JM, Lowrie EG. Comparing the urea reduction ratio and the urea product as outcome-based measures of hemodialysis dose. Am J Kidney Dis 2000; 35:598.
  80. Lowrie EG, Li Z, Ofsthun N, Lazarus JM. Body size, dialysis dose and death risk relationships among hemodialysis patients. Kidney Int 2002; 62:1891.
  81. Lowrie EG, Li Z, Ofsthun N, Lazarus JM. Measurement of dialyzer clearance, dialysis time, and body size: death risk relationships among patients. Kidney Int 2004; 66:2077.
  82. Lowrie EG, Lew NL. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 1990; 15:458.
  83. Iseki K, Kawazoe N, Fukiyama K. Serum albumin is a strong predictor of death in chronic dialysis patients. Kidney Int 1993; 44:115.
  84. Bommer J. If you wish to improve adequacy of dialysis, urea kinetics, such as Kt/V, may be the wrong parameter to study. ASAIO J 2001; 47:189.
  85. Mercadal L, Ridel C, Petitclerc T. Ionic dialysance: principle and review of its clinical relevance for quantification of hemodialysis efficiency. Hemodial Int 2005; 9:111.
  86. Di Filippo S, Manzoni C, Andrulli S, et al. Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients. Kidney Int 2004; 66:786.
  87. Gotch FA, Panlilio FM, Buyaki RA, et al. Mechanisms determining the ratio of conductivity clearance to urea clearance. Kidney Int Suppl 2004; :S3.