Rationale for Guideline Kt/V urea Targets for Hemodialysis

Hemodialysis Adequacy (Kt/V) Targets

Contribution from the KDOQI 2006 Hemodialysis Update workgroup

Source: KDOQI HD Adequacy guidelines for 2006 (National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for 2006 Updates: Hemodialysis Adequacy, Peritoneal Dialysis Adequacy and Vascular Access. Am J Kidney Dis 48:S1-S322, 2006 (suppl 1).

4.1. Minimally adequate dose:
The minimally adequate dose of HD given 3 times per week to patients with Kr less than 2 mL/min/1.73 m² should be a spKt/V (excluding RKF) of 1.2 per dialysis. For treatment times less than 5 hours, an alternative minimum dose is a URR of 65%.

Rationale: The Work Group realizes that the recently published European guidelines recommends substantially higher minimal doses of HD based on an eKt/V measure, (corresponding to spKt/V minimum targets of about 1.4 to 1.5) then those recommended by the NKF KDOQI guidelines. [1] The primary results of the HEMO Study, which randomized patients to a delivered eKt/V of 1.16 versus 1.53, however, revealed little evidence to support increasing the dose of dialysis beyond the current (2000) KDOQI recommendations. [2] The lack of benefit, without even a trend that was close to statistical significance, appeared not only in the primary outcome of mortality, but also in a variety of main secondary composite outcomes relating to various causes of hospitalization combined with mortality. Furthermore, analysis of minor secondary composite outcomes dealing with nutritional measures— including changes in weight and serum albumin levels, [3] as well as QOL measures [4]—also failed to support a beneficial effect of increasing the dose of dialysis. Of all trials evaluated, the HEMO Study was by far the largest, and its randomized design and measurement of hard outcomes were given an enormous weight in determining whether the 2000 KDOQI HD Adequacy Guidelines needed to be changed.

Since the KDOQI 2000 HD Adequacy guidelines were published, a number of studies, including analyses of USRDS Annual Data Reports, continued to examine the relationship between dose of dialysis and mortality. [5-9] Most of these analyses suggested that increasing the dose of dialysis above the target recommended in the 2000 guidelines to levels targeted in the high-dose arm of the HEMO Study (spKt/V ~ 1.7) should decrease mortality by a substantial amount. However, the lack of concordance between these observational results and negative results of the HEMO Study, coupled with the dose-targeting bias identified in the as-treated analysis of HEMO Study patients, restrained the Work Group from recommending a global increase in recommended spKt/V for patients dialyzed 3 times per week.

Many, including our European colleagues, [1] would like to convert the dose benchmark from spKt/V to eKt/V for HD (for PD, eKt/V and spKt/V are identical). Concern is raised about rapid dialysis in small patients, for whom the difference between spKt/V and eKt/V is larger than in patients of higher weight. After debating this issue in depth, the KDOQI HD Work Group unanimously decided to disallow shortened dialysis for treatments 3 times per week, but to do this explicitly rather than as a modification of Kt/V. Use of eKt/V as a benchmark does not prohibit ultrashort dialysis provided the clearance can be increased, for example, by increasing blood and dialysate flow rates or increasing dialyzer surface area. For such highly sequestered solutes as phosphate, however, this would not improve removal and the shortened dialysis time would compromise fluid removal. For pediatric and small adult patients, the size-associated mortality risk may be related in part to the shortened dialysis time often prescribed for small patients. Previous reports and recent evidence from DOPPS showing a positive correlation between dialysis treatment time and mortality support the concept that ultrashort dialysis (<3 hours), despite an adequate spKt/V, should be avoided. [10,11] Of note, the determination of eKt/V first requires measurement of spKt/V, and if the prescribed dose requires adjustment, conversion back to spKt/V is required to determine the change in dialyzer K that is required. Equilibrated K cannot be adjusted directly. In the absence of more evidence that would favor the additional effort and target range adjustment required to substitute eKt/V for spKt/V, the Work Group elected to stay with the currently established standard.

References:

1. European Best Practice Guidelines Expert Group on Hemodialysis, European Renal Association: Section II. Haemodialysis adequacy. Nephrol Dial Transplant 17:S16- S31, 2002 (suppl 7)
2. National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Hemodialysis Adequacy, 2000. Am J Kidney Dis 37:S7-S64, 2001 (suppl 1)
3. Rocco MV, Dwyer JT, Larive B, et al: The effect of dialysis dose and membrane flux on nutritional parameters in hemodialysis patients: Results of the HEMO Study. Kidney Int 65:2321-2334, 2004
4. 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 66:355-366, 2004
5. Owen WF Jr, Chertow GM, Lazarus JM, Lowrie EG: Dose of hemodialysis and survival: Differences by race and sex. JAMA 280:1764-1768, 1998
6. Port FK,Wolfe RA, Hulbert-Shearon TE, McCullough KP, Ashby VB, Held PJ: High dialysis dose is associated with lower mortality among women but not among men. Am J Kidney Dis 43:1014-1023, 2004
7. Port FK, Ashby VB, Dhingra RK, Roys EC, Wolfe RA: Dialysis dose and body mass index are strongly associated with survival in hemodialysis patients. J Am Soc Nephrol 13:1061-1066, 2002
8. Wolfe RA, Ashby VB, Daugirdas JT, Agodoa LY, Jones CA, Port FK: Body size, dose of hemodialysis, and mortality.Am J Kidney Dis 35:80-88, 2000
9. Chertow GM, Owen WF, Lazarus JM, Lew NL, Lowrie EG: Exploring the reverse J-shaped curve between urea reduction ratio and mortality. Kidney Int 56:1872-1878, 1999
10. Held PJ, Levin NW, Bovbjerg RR, Pauly MV, Diamond LH: Mortality and duration of hemodialysis treatment. JAMA 265:871-875, 1991
11. Saran R, Bragg-Gresham JL, Levin NW, et al: Longer treatment time and slower ultrafiltration in hemodialysis: associations with reduced mortality in the DOPPS. Kidney Int 69:1222-1228, 2006

Prepared on behalf of the National Kidney Foundation KDOQI guideline Peritoneal Dialysis workgroup by Michael Rocco (KDOQI Vice-Chair).