{"id":2776,"date":"2020-03-18T20:49:01","date_gmt":"2020-03-19T01:49:01","guid":{"rendered":"https:\/\/ami.advancedrenaleducation.com\/wparep\/?post_type=article&p=986"},"modified":"2025-09-02T11:19:25","modified_gmt":"2025-09-02T16:19:25","slug":"effect-of-dose","status":"publish","type":"article","link":"https:\/\/ami.advancedrenaleducation.com\/wparep\/asiapacific\/article\/effect-of-dose\/","title":{"rendered":"Effect of Dose"},"content":{"rendered":"
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The primary function of dialysis therapy is to remove waste products, retained solutes, and excess fluid that accumulate as a result of the failing kidneys. Physicians who prescribe hemodialysis need to determine the appropriate dose for individual patients and thus require a quantifiable measure that both reflects the efficacy of solute removal and serves as an indicator of HD treatment adequacy.<\/p>\n

 <\/p>\n

Establishing a quantifiable definition of dialysis dose<\/strong><\/p>\n

Initial efforts concentrated on the identification of the best uremic marker. This led to the square meter-hour hypothesis1<\/sup>, based on the view that toxins of middle molecular weight were mostly responsible for the uremic syndrome. Currently, however, small solute clearance, specifically urea kinetics, is the prevalent method for measuring delivered dialysis dose by measuring Kt\/V \u2013 the clearance of urea (K) multiplied by the length of the session (t) and divided by the total body water volume (V)2,3<\/sup>.<\/p>\n

Although urea is not a recognized uremic toxin, its increasing concentration in the blood during uremia is representative of other waste products building up, including ones that are not as readily measured4<\/sup>. Urea is a convenient index of dialysis performance owing to the fact that its concentration is easily and cost-effectively measured in blood and dialysate, it freely diffuses through compartments and the dialysis membrane, and is a good surrogate for dietary protein intake since it is the final product of protein metabolism3,4<\/sup>.<\/p>\n

The National Cooperative Dialysis Study (NCDS), a multicenter study of dialysis dose on clinical outcomes, was the first attempt to establish a more objective definition of dialysis adequacy5<\/sup>. Using urea and the length of dialysis sessions as proxies for small solute and middle molecular weight solute clearance, respectively, the study concluded that therapy focused on small solute removal resulted in lower mortality than a focus on treatment length5,6<\/sup>. A further mechanistic analysis of the NCDS, the first to define level of dialysis as Kt\/V, found that while morbidity decreased with increasing Kt\/V values through 0.9, there were no additional benefits of increasing dose from 0.9 to 1.5, concluding that a fully adequate dialysis prescription is provided with Kt\/V = 1.07<\/sup>. Almost two decades later, a large randomized controlled trial (RCT) called the Hemodialysis (HEMO) Study compared patients receiving thrice weekly HD for 2.5-4.5 hours in a standard-dose group (spKt\/V=1.32) and a high-dose group (spKt\/V=1.71) and confirmed the finding that mortality and secondary outcomes were not significantly influenced by dose8<\/sup>. Together, this evidence supports the National Kidney Foundation\u2019s Kidney Disease Outcomes Quality Initiative (NKF KDOQI) current guidelines, which recommend a minimally adequate target single pool Kt\/V (spKt\/V) of 1.4 per hemodialysis session for patients treated thrice weekly in order to achieve a minimum delivered spKt\/V of 1.23<\/sup>.<\/p>\n

 <\/p>\n

Assessing dose with more frequent HD treatments<\/strong><\/p>\n

Assessing adequacy of alternative, frequent HD prescriptions is different than in conventional, intermittent dialysis since urea concentrations become more stable with more frequent therapy and less urea is removed during each session. Urea generation by the body begins to equal urea removal by dialysis, and the single pool Kt\/V, with calculations based on the pre- and post- dialysis urea concentrations, no longer accurately reflects HD adequacy. The adequacy of more frequent home treatments is better assessed using the weekly standard Kt\/V (stdKt\/V). For HD schedules other than thrice weekly, NKF KDOQI recommends a stdKt\/V target of 2.3 per week, with a minimum delivered dose of 2.13<\/sup> (Figure 1).<\/p>\n

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Figure 1:<\/strong> Graphical model depicting relationship between single pool Kt\/V (values on the x-axis) and weekly standard Kt\/V (values on the y-axis). The number of sessions per week are shown on the right side and correspond to different line colors. The minimally adequate spKt\/V dose of 1.2 is roughly equivalent to a stdKt\/V of 2.1, as represented by the dashed lines. (Adapted from Gotch et al9<\/sup>)<\/h6>\n

 <\/p>\n<\/div>\n<\/div>\n

However, evaluating dose adequacy based solely on Kt\/V measures is limiting for several reasons. Several studies have suggested that the relationship between dialysis dose and survival depends on race, gender, and body size. Results from the HEMO Study suggested that mortality was lower in women receiving a higher dialysis dose8<\/sup>, and a subsequent study disproved body size differences alone as responsible for the gender effect10<\/sup>. Yet another found that dialysis dose and body size are independent correlates of mortality, with larger body size associated with lower mortality risk11<\/sup>. Current Kt\/V targets potentially underdose women and smaller men, who have higher rates of uremic toxin production and lower distribution volumes than larger patients12<\/sup>. Together, these studies show that patient demographics should be considered in the management of their dialysis regimen.<\/p>\n

Finally, although urea has traditionally been the most common indicator of dialysis dose, it is not representative of all uremic toxins and is influenced by nutritional status. Other markers of dialysis adequacy such as \u03b22-microglobulin, creatinine, phosphorus, parathyroid hormone, and serum albumin have been proposed, each with their own advantages and limitations13<\/sup>. While none of these individually is sufficiently reliable to replace Kt\/V, a combination of these markers could be useful to integrate into a patient\u2019s dialysis adequacy assessment.<\/p>\n

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*For a more detailed review of Kt\/V please reference our <\/strong>Measuring Hemodialysis Dose Article<\/a> on AREP.<\/strong><\/p>\n

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References:<\/h4>\n
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  1. Babb AL, Popovich RP, Christopher TG, Scribner B H. The genesis of the square meter-hour hypothesis. Trans Am Soc Artif Intern Organs<\/em>. 1971;17:81-91.<\/li>\n
  2. Gotch FA, Sargent JA, Keen ML. Whither goest Kt\/V? Kidney Int<\/em>. 2000;58:S3-S18.<\/li>\n
  3. National Kidney Foundation. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update. American Journal of Kidney Diseases<\/em>. 2015;66(5):884-930.<\/li>\n
  4. Locatelli F, Buoncristiani U, Canaud B, K\u00f6hler H, Petitclerc T, Zucchelli P. Dialysis dose and frequency. Nephrol Dial Transplant<\/em>. 2005;20(2):285-296. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/15598667.<\/li>\n
  5. 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<\/em>. 1981;305(20):1176-1181. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/7027040.<\/li>\n
  6. Lowrie EG, Chertow GM, Lew NL, Michael Lazarus J, Owen WF. The urea {clearance \u00d7 dialysis time} product (Kt) as an outcome-based measure of hemodialysis dose. Kidney Int<\/em>. 1999;56(2):729-737. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/10432415.<\/li>\n
  7. Gotch F, Sargent J. A mechanistic analysis of the National Cooperative Dialysis Study (NCDS). Kidney Int<\/em>. 1985;28(3):526-534. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/3934452.<\/li>\n
  8. Eknoyan G, Beck GJ, Cheung AK, et al. Effect of Dialysis Dose and Membrane Flux in Maintenance Hemodialysis. New England Journal of Medicine<\/em>. 2002;347(25):2010-2019. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12490682.<\/li>\n
  9. Gotch FA. The current place of urea kinetic modelling with respect to different dialysis modalities. Nephrol Dial Transplant<\/em>. 1998;13 Suppl 6:10-14. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/9719197.<\/li>\n
  10. 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<\/em>. 2004;65(4):1386-1394. Available from: http:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0085253815498485.<\/li>\n
  11. Wolfe RA, Ashby VB, Daugirdas JT, Agodoa LY, Jones CA, Port FK. Body size, dose of hemodialysis, and mortality. Am J Kidney Dis<\/em>. 2000;35(1):80-88. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/10620548.<\/li>\n
  12. Spalding EM, Chandna SM, Davenport A, Farrington K. Kt\/V underestimates the hemodialysis dose in women and small men. Kidney Int<\/em>. 2008;74(3):348-355.<\/li>\n
  13. Torreggiani M, Fois A, Njandjo L, et al. Toward an individualized determination of dialysis adequacy: a narrative review with special emphasis on incremental hemodialysis. Expert Rev Mol Diagn<\/em>. 2021;21(11):1119-1137.<\/li>\n<\/ol>\n

    GMO-001409\u00a0 Rev B\u00a0 11\/2024<\/span><\/p>\n

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