• Clinical practice guidelines for hemodialysis adequacy. Am J Kidney Dis 2006 Jul;48(1 Suppl 1):S13-97. [364 references]

This is the current release of the guideline.

This guideline updates a previous version: NKF-K/DOQI clinical practice guidelines for hemodialysis adequacy: update 2000. Am J Kidney Dis 2001 Jan;37(1 Suppl 1):S7-S64.

Definitions for the strength of each guideline (A, B, or CPR), based on the quality of the supporting evidence as well as additional considerations, are provided at the end of the "Major Recommendations" field.

Clinical Practice Guidelines (CPGs) for Hemodialysis Adequacy

Guideline 1. Initiation of Dialysis

1.1 Preparation for kidney failure:
Patients who reach chronic kidney disease (CKD) stage 4 (estimated glomerular filtration rate [GFR] < 30 mL/min/1.73 m²) should receive timely education about kidney failure and options for its treatment, including kidney transplantation, peritoneal dialysis (PD), hemodialysis (HD) in the home or in-center, and conservative treatment. Patients' family members and caregivers also should be educated about treatment choices for kidney failure. [B]

1.2 Estimation of kidney function:
Estimation of GFR should guide decision making regarding dialysis therapy initiation. GFR should be estimated by using a validated estimating equation (see Table 1 in the original guideline document) or by measurement of creatinine and urea clearances, not simply by measurement of serum creatinine and urea nitrogen. The tables below summarize special circumstances in which GFR estimates should be interpreted with particular care. [B]

Causes of Unusually Low or High Endogenous Creatinine Generation

Causes of Unusually Low or High Kidney Tubular Creatinine Secretion

1.3 Timing of therapy:
When patients reach stage 5 CKD (estimated GFR < 15 mL/min/1.73 m²), nephrologists should evaluate the benefits, risks, and disadvantages of beginning kidney replacement therapy. Particular clinical considerations and certain characteristic complications of kidney failure may prompt initiation of therapy before stage 5. [B]

Guideline 2. Methods for Measuring and Expressing the Hemodialysis Dose

Quantifying HD is the first step toward assessment of its adequacy. Fortunately, the intermittent rapid decrease in urea concentration during HD allows a relatively easy measurement of the dose.

2.1 The delivered dose of HD should be measured at regular intervals no less than monthly. [A]
2.2 The frequency of treatments should be included in the expression of dose. [A]
2.3 The dose of HD should be expressed as (K_urea  x T_d)/V_urea (abbreviated as Kt/V), where K_urea is the effective (delivered) dialyzer urea clearance in milliliters per minute integrated over the entire dialysis, T_d is the time in minutes measured from beginning to end of dialysis, and V_urea is the patient's volume of urea distribution in milliliters. [B]
2.4 The preferred method for measurement of the delivered dose is formal urea kinetic modeling. Other methods may be used provided they give similar results and do not significantly overestimate the modeled dose. [A]
2.5 Methods described in the appendix of the original guideline document can be used to add the continuous component of residual urea clearance to the intermittent dialysis single-pool delivered Kt/V* (spKt/V) to compute an adjusted intermittent Kt/V. Laboratories reporting adjusted session Kt/V values should clearly identify such measurements by a different name (e.g., "adjusted" Kt/V or "total" Kt/V). [B]

*By dialysis only, exclusive of residual kidney function (RKF)

Guideline 3. Methods for Postdialysis Blood Sampling

When dialysis adequacy is assessed by using predialysis and postdialysis blood urea nitrogen (BUN) measurements, blood samples should be drawn by using certain acceptable procedures.

3.1 Both samples (predialysis and postdialysis) should be drawn during the same treatment session. [A]
3.2 The risk of underestimating predialysis BUN level because of saline dilution or by sampling the blood after treatment has begun should be avoided. [A]
3.3 The risk of underestimating the postdialysis BUN level because of access recirculation (AR) should be avoided by first slowing the blood flow through the dialyzer to a rate at which AR is expected to be minimal (100 mL/min) for a period long enough to ensure that unrecirculated blood has advanced to below the sampling port (usually 15 seconds). [A]
3.4 An alternative method is to stop the dialysate flow for a period long enough to increase the dialysate outlet BUN level close to that of the blood inlet BUN level (3 minutes) before obtaining the postdialysis sample. [A]

Recommended Predialysis Blood-Drawing Procedure

Slow-Blood-Flow Method for Obtaining the Postdialysis Sample

HD: Hemodialysis; UFR: Ultrafiltration rate; TMP: Transmembrane pressure

Stop-Dialysis-Flow Method of Obtaining the Postdialysis Sample

HD: Hemodialysis; UFR: Ultrafiltration rate; TMP: Transmembrane pressure

Guideline 4. Minimally Adequate Hemodialysis

4.1 Minimally adequate dose:
The minimally adequate dose of HD given 3 times per week to patients with residual native kidney urea clearance (K_r) less than 2 mL/min/1.73 m² should be an spKt/V (excluding RKF) of 1.2 per dialysis. For treatment times less than 5 hours, an alternative minimum dose is a urea reduction ratio (URR) of 65%. [A]
4.2 Target dose:
The target dose for HD given 3 times per week with Kr less than 2 mL/min/1.73 m² should be an spKt/V of 1.4 per dialysis not including RKF, or URR of 70%. [A]
4.3 In patients with residual urea clearance (Kr) greater than or equal to 2 mL/min/1.73 m², the minimum session spKt/V can be reduced. One method of minimum dose reduction is described in CPR 4.4. In such patients, the target spKt/V should be at least 15% greater than the minimum dose. [B]
4.4 Missed and shortened treatments:
Efforts should be made to monitor and minimize the occurrence of missed or shortened treatments. [B]

Guideline 5. Control of Volume and Blood Pressure

There is ample evidence in the non-CKD population that optimal control of blood pressure influences mortality. In the HD population, available evidence indicates that control of a patient's fluid volume influences outcome. Volume and blood pressure are linked; thus, it is important to optimize ultrafiltration and dry weight to control blood pressure in an effort to improve patient outcome.

5.1 The ultrafiltration component of the HD prescription should be optimized with a goal to render the patient euvolemic and normotensive. This includes counseling the patient on sodium and fluid restriction, adequate ultrafiltration, and the use of diuretics in patients with RKF. [A]
5.2 Daily dietary sodium intake should be restricted to no more than 5 g of sodium chloride (2.0 g or 85 mmol of sodium). [A]
5.3 Increasing positive sodium balance by "sodium profiling" or using a high dialysate sodium concentration should be avoided. [B]

Guideline 6. Preservation of Residual Kidney Function

Prospective randomized trials and observational studies have confirmed that the presence of RKF is one of the most important predictors of a patient's survival.

6.1 One should strive to preserve RKF in HD patients. [A]
6.2 Methods for preserving RKF differ among patients (see CPR 6). [B]

Guideline 7. Quality Improvement Programs

The continuous quality improvement (CQI) process has been shown to improve clinical outcomes in many disciplines, including CKD. It presently is conducted at both the facility level and local network level.

7.1 For HD adequacy, each dialysis clinic should continue to monitor the processes related to the delivery of dialysis, such as Kt/V, reuse standards, etc. [A]
7.2 Consideration should be given to providing resources and training for expanding the assessment of clinical outcomes beyond mortality to include hospitalization rates, quality of life (QOL), patient satisfaction, and transplantation rates, recognizing that without adequate resources and training, these outcomes are unlikely to be valid, and the efforts to collect such information may adversely affect patient care. [B]
7.3 Quality improvement programs should include representatives of all disciplines involved in the care of HD patients, including physicians, physician assistants, nurse practitioners, nurses, social workers, dietitians, and administrative staff. [B]

Guideline 8. Pediatric Hemodialysis Prescription and Adequacy

8.1 Initiation of HD:

8.1.1 Dialysis initiation considerations for the pediatric patient should follow the adult patient guideline of a GFR less than 15 mL/min/1.73 m². [A]

8.1.2 For pediatric patients, GFR can be estimated by using either a timed urine collection or the Schwartz formula. [A]

8.1.3 Dialysis therapy initiation should be considered at higher estimated GFRs when the patient's clinical course is complicated by the presence of the signs and symptoms listed in the table below, Clinical Practice Recommendation (CPR) 1 for adult patients, ("Complications That May Prompt Initiation of Kidney Replacement Therapy"), as well as malnutrition or growth failure for pediatric patients. Before dialysis is undertaken, these conditions should be shown to be refractory to medication and/or dietary management. [A]

8.2 Measurement of HD adequacy:

8.2.1 spKt/V, calculated by either formal urea kinetic modeling or the second-generation natural logarithm formula, should be used for month-to-month assessment of delivered HD dose. [B]

8.2.2 Assessment of nutrition status is an essential component of HD adequacy measurement. Normalized protein catabolic rate (nPCR) should be measured monthly by using either formal urea kinetic modeling or algebraic approximation. [B]

8.2.3 Principles and statements regarding slow-flow methods for postdialysis sampling and inclusion of RKF (or lack thereof) outlined in the adult guidelines also pertain to pediatric patients. [B]

8.3 Prescription of adequate HD:

8.3.1 Children should receive at least the delivered dialysis dose as recommended for the adult population. [A]

8.3.2 For younger pediatric patients, prescription of higher dialysis doses and higher protein intakes at 150% of the recommended nutrient intake for age may be important. [B]

8.4 Non–dose-related components of adequacy:
Accurate assessment of patient intravascular volume during the HD treatment should be provided to optimize ultrafiltration. [B]

Clinical Practice Recommendations (CPRs) for Hemodialysis Adequacy

Clinical Practice Recommendation for Guideline 1: Initiation of Dialysis

Certain complications of kidney failure justify initiation of dialysis treatment in patients for whom estimated GFR has not yet decreased to 15 mL/min/1.73 m² (see table below).

Complications That May Prompt Initiation of Kidney Replacement Therapy

ECV: Extracellular Volume

Clinical Practice Recommendations for Guideline 2: Methods for Measuring and Expressing the Hemodialysis Dose

For patients managed with HD, both dialyzer and native kidney function can be measured periodically to assess the adequacy of replacement therapy. Urea clearance is the preferred measure of both (see CPG 2).

2.1 Residual kidney urea clearance (K_r) is measured best from a timed urine collection.
2.2 For purposes of quality assurance, the delivered dose should be measured and compared with the prescribed dose each month.

Clinical Practice Recommendations for Guideline 4: Minimally Adequate Hemodialysis

4.1 High-Flux Membrane:
When methods to achieve good dialysate water quality are available, high-flux HD membranes should be used, defined as those providing Beta₂-microglobulin (Beta2M) clearance of at least 20 mL/min under conditions of actual use.
4.2 Minimum dose with hemofiltration or hemodiafiltration:
The recommended minimum delivered dose target, measured by using pretreatment and posttreatment BUN levels, is the same as that for HD.
4.3 Minimum spKt/V levels for different dialysis schedules:

4.3.1 Two to 6 treatments per week are appropriate for certain patients.

4.3.2 Twice-weekly HD is not appropriate for patients with K_r less than 2 mL/min/1.73 m².

4.3.3 Minimum spKt/V targets for 2-, 4-, and 6-times-per-week dialysis schedules logically should be different from that for the thrice-weekly schedule. In the absence of dose-ranging outcomes data, minimum spKt/V targets for different schedules can be based on achieving a minimum standard Kt/V (stdKt/V) of 2.0 per week.

4.3.4 The target spKt/V dose should be at least 15% higher than the listed minimum dose because of the variability in measuring Kt/V, as discussed in Guideline 4.

4.4 RKF (measured by K_r):

4.4.1 The minimally adequate dose of dialysis can be reduced in patients with K_r greater than 2 mL/min/1.73 m².

4.4.2 In the absence of dose-ranging outcomes data, the minimum spKt/V target for patients with substantial RKF can be reduced, but the reduced target should be no lower than 60% of the minimum target for patients with no residual renal function (the reduction depends on dialysis frequency), per values provided in Table 13 of the original guideline document.

4.4.3 When the minimally adequate dose is reduced because of substantial RKF, K_r should be monitored at least quarterly and as soon as possible after any event that might have acutely reduced RKF.  

4.5 Increase in minimally adequate dose for women and smaller patients:

An increase in the minimally adequate dose of dialysis should be considered for the following groups of patients:

4.5.1 Women of any body size.

4.5.2 Smaller patients, for example, patients with values for anthropometric or modeled volume (V) of 25 L or lower.

4.6 Dialysis adequacy for patients who are malnourished and/or losing weight:
An increase in the minimally adequate dose of dialysis and/or a change to a more frequent dialysis schedule should be considered for the following groups of patients:

4.6.1 Patients whose weights are 20% less or lower than their peer body weights.

4.6.2 Patients with recent otherwise unexplained and unplanned weight loss.

4.7 Dialysis adequacy for patients with hyperphosphatemia or chronic fluid overload and other categories of patients who might benefit from more frequent dialysis:
A change to a more frequent dialysis schedule should be considered for the following groups of patients:

4.7.1 Patients with hyperphosphatemia.

4.7.2 Patients with chronic fluid overload with or without refractory hypertension.

4.8 A change to a more frequent dialysis schedule may be beneficial to a broader group of patients in terms of improving Quality of Life (QOL) and quality of sleep, reducing sleep apnea, and improving sensitivity to erythropoietin.
4.9 Minimum dialysis treatment time for thrice-weekly schedules:
The minimum HD treatment time for thrice-weekly dialysis in patients with K_r less than 2 mL/min should be at least 3 hours.

Clinical Practice Recommendations for Guideline 5: Dialyzer Membranes and Reuse

Selection of dialyzer membranes and reuse practices are not included in the prescription of small-solute clearance, yet they can be important determinants of patient survival and QOL.

5.1 When dialyzers are reused, they should be reprocessed following the Association for the Advancement of Medical Instrumentation (AAMI) Standards and Recommended Practices for reuse of hemodialyzers (Association for Advancement of Medical Information [AAMI], 2003).
5.2 Dialyzers intended for reuse should have a blood compartment volume not less than 80% of the original measured volume or a urea (or ionic) clearance not less than 90% of the original measured clearance.
5.3 The use of poorly biocompatible, unmodified cellulose dialyzer membranes for HD is discouraged.

Clinical Practice Recommendations for Guideline 6: Preservation of Residual Kidney Function

Several actions and precautions are recommended to preserve and enhance RKF.

6.1 Angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) are agents of choice in HD patients with significant RKF and who need antihypertensive medication. Other measures to protect native kidneys are listed in the following table.

Efforts to Protect RKF

COX-2: Cyclooxygenase-2; ACE: Angiotensin-converting enzyme; ARB: Angiotensin receptor blockers

6.2 Insults known to be nephrotoxic (e.g., see table below) in patients with normal or impaired kidney function should be assumed, in the absence of direct evidence, to be nephrotoxic for the remnant kidney in HD patients and therefore should be avoided.
6.3 Prerenal and postrenal causes of decrease in RKF should be considered in the appropriate clinical setting.

Potential Insults to RKF

COX-2: Cyclooxygenase-2; ECF: Extracellular fluid

Definitions:

Rating the Strength of Guideline Recommendations

The strength of each guideline recommendation is based on the quality of the supporting evidence as well as additional considerations. Additional considerations, such as cost, feasibility, and incremental benefit were implicitly considered.

A It is strongly recommended that clinicians routinely follow the guideline for eligible patients. There is strong evidence that the practice improves health outcomes.

B It is recommended that clinicians routinely follow the guideline for eligible patients. There is moderately strong evidence that the practice improves health outcomes.

CPR It is recommended that clinicians consider following the guideline for eligible patients. This recommendation is based on either weak evidence or on the opinions of the Work Group and reviewers that the practice might improve health outcomes.

Health outcomes are health-related events, conditions, or symptoms that can be perceived by individuals to have an important effect on their lives. Improving health outcomes implies that benefits outweigh any adverse effects.

Rating the Quality of Evidence

The quality of evidence was not explicitly graded. It was implicitly assessed according to the criteria outlined in the table below, and considered: i) the methodological quality of the studies; ii) whether or not the studies were carried out in the target population (i.e., patients on dialysis, or in other populations); and iii) whether the studies examined health outcomes directly, or examined surrogate measures for those outcomes (e.g., blood flow instead of access survival).

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations")."

• Clinical practice guidelines for hemodialysis adequacy. Am J Kidney Dis 2006 Jul;48(1 Suppl 1):S13-97. [364 references]

Not applicable: The guideline was not adapted from another source.

1997 (updated 2006 Jul)

National Kidney Foundation - Disease Specific Society

National Kidney Foundation (NKF)

NKF-K/DOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) Hemodialysis Adequacy Working Group

Work Group Members: Thomas A. Depner, MD (Co-Chair) University of California, Davis, Sacramento, CA; John T. Daugirdas, MD (Co-Chair) University of Illinois Medical Center, Chicago, IL; Stuart Goldstein, MD, Baylor College of Medicine, Texas Children's Hospital, Houston, TX; Todd S. Ing, MD, Hines VA/Loyola University Medical Center, Wilmette, IL; Victoria Kumar, MD, University of California, Davis, Kaiser Permanente Medical Group, Los Angeles, CA; Klemens B. Meyer, MD, Tufts University School of Medicine-New England Medical Center, Boston, MA; Keith Norris, MD, Dean of Research, Charles R. Drew University, Lynwood, CA

Evidence Review Team: Ethan Balk, MD, MPH, Project Director, Hemodialysis and Peritoneal Dialysis Adequacy; Katrin Uhlig, MD, Project Director, Vascular Access; George Fares, MD, Assistant Project Director, Hemodialysis and Peritoneal Dialysis Adequacy; Ashish Mahajan, MD, MPH, Assistant Project Director, Vascular Access, Hemodialysis and Peritoneal Dialysis Adequacy; Amy Earley, BS; Rebecca Persson, BA; Gowri Raman, MD; Christina Kwack Yuhan, MD; Priscilla Chew, MPH; Stanley Ip, MD; Mei Chung, MPH

The National Kidney Foundation makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the Work Group.

Specifically, all members of the Work Group are required to complete, sign, and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

• Dr. Daugirdas has received grants from Watson, American Regent, Aksys, Nephros, RRI, HDC Medical, Advanced Renal Technologies, Amgen, Ortho Biotech, Shire, Roche, Astra Zeneca, and Neurochem.
• Dr. Goldstein has received grants from Gambro Renal Products, Dialysis Solutions Inc, Baxter Healthcare, B. Braun Inc, Amgen Inc, Abbott Laboratories, and Toray Inc. He has also lectured for Genentech. Dr Goldstein has received research funds, grants, or contracts from American Academy of Pediatrics, Baxter Healthcare, Dialysis Solutions, Inc., Gambro Renal Products, Genentech, Luitpold Pharmaceuticals, NxStage Inc., and The University of Missouri.
• Dr Ing has received research funds, grants, or contracts from Abbott Laboratories and Aksys Ltd.
• Dr Meyers has received research funds, grants, or contracts from Primary Insight Contributor Network, MEDA Corp/Leerink Swann & Co., and Gerson Lehram Healthcare Council.
• Dr Norris has received research funds, grants, or contracts from Abbott Laboratories, Amgen, Genzyme/Bone Care International, Merck, and Pfizer.

This is the current release of the guideline.

This guideline updates a previous version: NKF-K/DOQI clinical practice guidelines for hemodialysis adequacy: update 2000. Am J Kidney Dis 2001 Jan;37(1 Suppl 1):S7-S64.

None available

None available

This summary was completed by ECRI on September 1, 2001. The information was verified by the guideline developer as of November 19, 2001. This summary was updated by ECRI on December 18, 2006. This summary was updated by ECRI Institute on July 9, 2007, following the FDA advisory on erythropoiesis stimulating agents. This summary was updated by ECRI Institute on March 21, 2008 following the FDA advisory on Erythropoiesis Stimulating Agents. This summary was updated by ECRI Institute on August 15, 2008 following the U.S. Food and Drug Administration advisory on Erythropoiesis Stimulating Agents (ESAs).

K/DOQI is a trademark of the National Kidney Foundation, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage retrieval system, without permission in writing from the National Kidney Foundation.