Rationale for Guideline Kt/V urea Targets for Hemodialysis

Hemodialysis Adequacy (Kt/V) Targets

Contribution from UK Renal Association Clinical Practice Guidelines Committee

The current 3^rd edition of the Renal Association “Standards” states:

Every patient receiving thrice weekly HD should show:

either urea reduction ratio (URR) consistently >65%
or equilibrated Kt/V of >1.2 (calculated from pre- and post-dialysis urea values, duration of dialysis and weight loss during dialysis). (Evidence grade B)

In the updated 4^th edition (now called the Renal Association Clinical Practice Guidelines) this statement has been only slightly modified:

Every patient with end-stage chronic renal failure receiving thrice weekly HD should have consistently:

either urea reduction ratio (URR) > 65%
or equilibrated Kt/V of >1.2 (or single pool Kt/V (sp Kt/V) of > 1.3) calculated from pre- and post-dialysis urea values, duration of dialysis and weight loss during dialysis (Evidence)

Rationale: To achieve a URR above 65% or equilibrated Kt/V (eKT/V) above 1.2 consistently in the vast majority of the haemodialysis population clinicians should aim for a minimum target URR of 70% or minimum eKt/V of 1.4 in individual patients. Aiming for these target doses also addresses the concerns raised by recent data that suggest that women and patients of low body weight may have improved survival rates if the URR is maintained above 70% or eKt/V is at least 1.4.

The optimal dialysis dose has not been well defined but minimum targets of delivered dose measured by URR and Kt/V have been established. A retrospective analysis of the National Co-operative Dialysis Study suggested that a Kt/V of 1.0 was the watershed between ‘good’ dialysis t/V >1.0) and inadequate dialysis (Kt/V <1.0). Thereafter Kt/V survived as an index of dialysis adequacy¹. More recent udies^2-7 have shown a reduction in mortality rates with increases in dialysis dose measured in various ways with some of the studies adjusting for co-morbidity^{3, 7}. One study has shown no further reduction in mortality above Kt/V of 1.3 or URR of 70%². Many commentators, however, believed that some further improvement in mortality risk could be achieved with Kt/Vs of up to 1.6 or even higher^8-10. The HEMO trial was a prospective randomised controlled trial in which 1846 patients were randomised to achieve a standard-dose goal of an eKt/V of 1.05 (URR circa 65%) or a high-dose goal of an eKt/V of 1.45 (URR circa 75%) and to synthetic or semi-synthetic membranes of high or low flux in a 2 x 2 factorial design¹¹. This study showed no difference in patient survival or secondary end-points between the two groups after a mean follow-up period of 2.8 years. No difference in patient outcomes was observed in the two groups even although dialysis doses were well separated with achieved eKt/V of 1.16 in the standard-dose group spKt/V 1.3 + 0.1; URR 66.3 + 2.5%) and eKt/V of 1.53 in the high-dose group (spKt/V 1.7 + 0.1; URR 75.2 + 2.5%).

Subgroup analysis of the HEMO study showed that survival rates in women randomized to the higher dose group were higher than women in the lower dose group (relative risk 0.81; p = 0.02) and this association persisted after adjusting for different indices of body size¹². An association between higher dose and lower mortality rates in women but not in men was confirmed using the average URR of incident HD patients in the USA and eKt/V of HD patients in the DOPPS data from 7 countries¹³. Further analyses of the HEMO study showed that differences in dialysis dose and membrane flux had no effect on the proportion of infection-related deaths¹⁴.

Based upon the above evidence we have retained the standard dose as a URR of 65% or an eKt/V of 1.2 in the 4^th edition of the Renal Association Clinical Practice Guidelines. This should be regarded as the minimum dialysis dose delivered thrice weekly. To ensure as many patients as possible achieve this standard consistently the target dose should be a URR of 70% or eKt/V of 1.4.

References:

1. Gotch FA, Sargent JA. A mechanistic analysis of the National Cooperative Dialysis Study (NCDS). Kidney Int 1985; 28:526–534
2. Held PJ, Port FK, Wolfe RA et al. The dose of hemodialysis and patient mortality. Kidney Int 1996; 50:550–556
3. 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; 9:1940–1947
4. Parker T, Husni L, Huang W et al. Survival of haemodialysis patients in the United States is improved with a greater quantitiy of dialysis. Am J Kidney Dis 1994; 23: 670-680
5. Hakim RM, Breyer J, Ismail N, Schulman G. Effects of dose of dialysis on morbidity and mortality. Am J Kidney Dis 1994; 23:661–669
6. Collins AJ, Ma JZ, Umen A et al. Urea index and other predictors of hemodialysis patient survival. Am J Kidney Dis 1994; 23:272–282
7. Bloembergen WE, Hakim RM, Stannard DC et al. Relationship of dialysis membrane and cause-specific mortality. Am J Kidney Dis 1999; 33:1–10
8. Hornberger JC. The hemodialysis prescription and quality-adjusted life expectancy. Renal Physicians Association Working Committee on Clinical Guidelines. J Am Soc Nephrol 1993; 4:1004–1020
9. Hornberger JC. The hemodialysis prescription and cost effectiveness. Renal Physicians Association Working Committee on Clinical Guidelines. J Am Soc Nephrol 1993; 4:1021–1027
10. Wolfe RA, Ashby VB, Daugirdas JT et al. Body size, dose of hemodialysis, and mortality. Am J Kidney Dis 2000; 35:80–88
11. Eknoyan G, Beck GJ, Cheung AK et al. Effect of dialysis dose and flux on mortality and morbidity in maintenance hemodialysis patients: Primary results of the HEMO study. N Engl J Med 2002; 347:2010-2019
12. 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: 1386-1394
13. 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: 1014-1023
14. Allon M. Depner TA, Radeva M, et al. Impact of dialysis dose and membrane on infection-related hospitalisation and death: Results of the HEMO study. J Am Soc Nephrol 2003; 14: 1863- 1870

Prepared on behalf of the UK Renal Association Clinical Practice Guidelines Committee by Robert MacTier and David Wheeler (Chairman).