KDOQI Update 2000



NOTE: The citation for these guidelines should read as follows: National Kidney Foundation. KDOQI Clinical Practice Guidelines for Hemodialysis Adequacy, 2000. Am J Kidney Dis 37:S7-S64, 2001 (suppl 1)


APPROXIMATELY 284,000 Americans suffered from end-stage renal disease (ESRD) in 1996,1 of whom 62% were treated by maintenance hemodialysis (HD).2 Despite a longer life expectancy for the general population of the United States in comparison to that of most other industrialized nations, several analyses have reported that the gross and adjusted annual mortality of Americans with ESRD greatly exceeds the analogous rates observed in other countries.3-8 Several explanations have been proposed for these differences in ESRD patient outcome, including:

1. The acceptance of patients for maintenance dialysis in the United States who are relatively older and/or have more comorbidity than dialysis patients in other countries.9,10

2. Genetic differences between the prevalent patient populations in the United States and abroad that confer differing risks for comorbid conditions such as cardiovascular disease.11

3. The prevalent practice in the United States of dialyzer reuse (81% of dialysis centers in 1996) that may expose hemodialysis patients to toxic chemicals, increased risk of infection, and/or less effective dialysis due to compromised dialyzer function.12-17

4. The lower tendency in the United States to adequately meet the nutritional needs of hemodialysis patients.18-21

5. The incomplete and/or inaccurate reporting of relevant patient comorbidity and outcomes by non-US ESRD registries.7,22-25

6. The lower tendency to deliver an adequate dose of hemodialysis to patients in the United States.14,18,19,26-32

Regardless of the precise reasons for the apparent difference in outcome between Americans with ESRD and patients from other industrialized nations, it is indisputable that the delivered dose of hemodialysis is a significant predictor of patient outcome19,33-42 and that the dose of hemodialysis provided to many American patients can and should be increased.19,27,29-31,43 This assertion is based on several premises, including:

1. The dose of hemodialysis can be measured precisely, reproducibly, and routinely in the clinical setting.19,34,42-50

2. A scientific consensus exists on what constitutes an adequate dose of hemodialysis.51,52

3. Many patients do not receive that dose of hemodialysis.19,31,43,53-57

4. Reasons for deficiencies in the delivered dose of dialysis can be identified and redressed.35,51,53-55,58-61

The Renal Physicians Association’s (RPA) 1993 Clinical Practice Guideline on Adequacy of Hemodialysis* describes acceptable methods for measuring hemodialysis adequacy and defines a minimum acceptable delivered dose of hemodialysis for adults (>18 years old) with ESRD who have negligible residual kidney function and are receiving outpatient hemodialysis three times per week. Specifically, the RPA recommended that the variable volume, single-pool model of urea kinetic modeling (Kt/Vd) should be measured monthly to assure the adequacy of hemodialysis (HD), such that patients receive the full benefit of HD for ESRD. The recommended Kt/Vd should be at least 1.2 (urea reduction ratio 65%). When the Kt/Vd falls below this level, corrective action should be undertaken.51

The NKF-KDOQI HD Adequacy Work Group identified several topics pertinent to implementing and maintaining adequate hemodialysis that had received limited attention in the RPA’s Clinical Practice Guideline on Adequacy of Hemodialysis. As a result, the NKF-KDOQI Work Group summarized data and developed recommendations that supplement the RPA guideline in the following areas:

1. Optimum hemodialysis dose.

2. Adequacy of hemodialysis for pediatric patients.

3. Blood sampling to measure the hemodialysis dose.

4. Reuse of hemodialyzers.

5. Patient comfort and adherence.


Optimum Hemodialysis Dose

The RPA’s Clinical Practice Guideline on Adequacy of Hemodialysis described a minimum delivered dose of hemodialysis for adults with no residual kidney function who were receiving hemodialysis three times per week. In this respect, the RPA’s Clinical Practice Guideline on Adequacy of Hemodialysis did not describe a dose of hemodialysis that maximizes the survival, health, and quality of life of ESRD patients. In the absence of financial constraints, a dose of dialysis that maximizes patient outcomes is the optimal dose of hemodialysis and is a more appropriate target for prescribed dialysis therapy than a minimum adequate dialysis dose. The HD Adequacy Work Group examined peer-reviewed literature published since the release of the RPA guideline in an attempt to define an optimal delivered dose of hemodialysis. Because of changes in the demographics of the ESRD population, eg, an aging ESRD population, an increasing prevalence of patients with diabetes mellitus,1 the HD Adequacy Work Group considered what constitutes a minimum adequate dose for different subpopulations. Selected patient subsets (blacks and diabetics) were examined to determine if the minimum hemodialysis dose for them should differ from that for the rest of the dialysis population.

Because of inappropriate timing of acquisition of the postdialysis blood urea nitrogen (BUN) sample in many patients, some of the apparent improvement in hemodialysis adequacy that has been reported may be spurious.62-64 Therefore, significant opportunities for improvement still exist. The HD Adequacy Work Group developed an algorithm that details recommended procedures for identifying and correcting deficiencies in the delivered dose of dialysis. The intent of the algorithm is to help dialysis care teams:

1. recognize deficiencies in the delivered dose of hemodialysis.

2. identify the cause(s) of inadequate delivered dose of hemodialysis.

3. correct the cause(s) of inadequate delivered dose of hemodialysis.

Adequacy of Hemodialysis for Pediatric Patients

Pediatric patients comprise less than 1% of the total hemodialysis patient population, even in industrialized countries with established pediatric ESRD treatment capabilities. In the United States, the point prevalence of ESRD patients less than 20 years of age was 4,777 per million in 1994-1996. Eighteen percent of ESRD patients less than 20 years old received maintenance hemodialysis.1,65 There are two predominant reasons for the small number of pediatric as compared with adult patients. First, ESRD is not a common pediatric disorder. Its incidence in pediatric patients is just over 15 new patients per million per year. In contrast, incidence rates are 122/million/yr for people 20 to 44 years of age.1,65 Second, most children spend a relatively short time on dialysis, typically only the time awaiting kidney transplantation. As a result, even the largest pediatric hemodialysis programs are quite small by adult program standards and rarely exceed 10 to 15 patients per facility.

There are few reports in the medical literature of studies involving pediatric hemodialysis patients and no data on outcomes as a function of hemodialysis dose in children. Previous efforts to develop guidelines for hemodialysis, including the RPA’s Clinical Practice Guideline on Adequacy of Hemodialysis, did not address pediatric patients. The HD Adequacy Work Group recognized the paucity of data on adequacy of hemodialysis in pediatric patients, and decided that it was desirable and possible to extend the guideline development process to children. All available pediatric hemodialysis literature was reviewed; where pediatric data were lacking, the Work Group extrapolated from adult patient data. Thus, the NKF-KDOQI Clinical Practice Guidelines for Hemodialysis Adequacy addresses children as well as adults.

Blood Sampling Procedure

Considerable variability in sampling procedures exists in dialysis practice in the United States. For example, 33% of the hemodialysis units represented by members of the Medical Review Board of the ESRD Network of New England (ESRD Network 1) reported that the samples for testing postdialysis BUN were drawn immediately before the hemodialysis treatment was terminated, 25% obtained samples immediately after the end of the dialysis treatment, and 42% drew the sample 5 minutes after all blood was reinfused into the patient.62 Similar procedural inconsistency has been observed in ESRD Network 16. Data for all hemodialysis patients in Network 16 suggest that postdialysis BUN samples were drawn immediately upon the completion of dialysis at 21% of the dialysis facilities, after an interval of 1 to 2 minutes at 52% of the facilities, 2 to 10 minutes after the completion of dialysis at 15% of the facilities, and more than 10 minutes after completion of dialysis at 13% of facilities.43 During 1993, the United States Renal Data System (USRDS) reported that, in the dialysis facilities surveyed, the postdialysis BUN sample was drawn immediately at the end of hemodialysis without changes in the blood flow at 15% of facilities, immediately upon ending hemodialysis with a slowing or stopping of the blood pump at 48% of facilities, 20 to 60 seconds after the end of dialysis at 9% of facilities, 1 to 2 minutes after the end of dialysis at 12% of facilities, 3 to 15 minutes after the end of dialysis at 15% of facilities, and more than 15 minutes after the completion of dialysis at 1% of facilities.66 Because of inappropriate timing of the acquisition of postdialysis blood samples, the actual delivered dose of hemodialysis may be overestimated.47,58,67,68 A 1995 survey of 195 dialysis units in the United States found that 5% and 42% of the centers used predialysis and postdialysis blood drawing procedures, respectively, that were judged to be erroneous.64 Erroneous blood drawing techniques and needless procedural variability compromise the ability to compare the dose of hemodialysis delivered by different dialysis units, even when the same formulae for calculating Kt/V are used. More precise specification of appropriate procedural technique will increase the accuracy and comparability of measured hemodialysis doses. To address this problem, the HD Adequacy Work Group developed supplemental procedural guidelines for predialysis and postdialysis BUN sampling.

Reuse of Dialyzers

Predominantly for economic reasons, reuse of hemodialyzers is a prevalent practice in the United States.16,17,69-71 In 1993, approximately 79% of adult hemodialysis patients used reprocessed dialyzers. Data describing the prevalence of dialyzer reuse among pediatric hemodialysis patients are not available. Because the essential function of a hemodialyzer is to permit the mass transfer of solutes from the patient’s blood into the dialysate and vice versa, the solute transport capacity or clearance of a hemodialyzer is a critical variable in writing and delivering an adequate hemodialysis prescription. Reuse of a hemodialyzer can change its solute transport capacity.72,73 For this reason, clinicians need an accurate assessment of the solute clearance of the hemodialyzer. In the absence of direct measures of change in solute clearance with reuse, change in the total cell volume (TCV), also described as the fiber bundle volume, has been the conventional surrogate used to monitor changes in solute transport characteristics for hollow fiber dialyzers.74,75 Several factors prompted the HD Adequacy Work Group to evaluate the use of TCV as a measure of clearance, including:

● The TCV is an indirect measure of solute clearance.

● Reprocessing techniques have evolved.

The HD Adequacy Work Group examined the peer-reviewed literature and the Association for the Advancement of Medical Instrumentation Standards and Recommended Practices for Reuse of Hemodialyzers.76

Patient Comfort and Adherence

The HD Adequacy Work Group recognizes that a major barrier to providing adequate hemodialysis is patient nonadherence with the hemodialysis prescription. Patients may confound the health care teams’ attempts to provide an otherwise adequate treatment by missing hemodialysis sessions, arriving late for treatments, temporarily interrupting the treatment, or discontinuing the hemodialysis session prematurely.32,53,77,78 The RPA’s Clinical Practice Guideline on Adequacy of Hemodialysis focused on the processes of patient care necessary to provide an adequate dose of hemodialysis, but did not offer clinical strategies and interventions to enhance patient acceptance of the hemodialysis prescription. The HD Adequacy Work Group examined the peer-reviewed literature to identify strategies that minimize patient discomfort during and immediately after hemodialysis treatments. Complications, such as hypotension and cramps, that would compromise patient acceptance of hemodialysis, were a major focus.

In 1997, the NKF-DOQI HD Adequacy Work Group published the initial version of their evidence-based clinical practice guideline for hemodialysis adequacy.52 In brief, the guidelines recommended:

1. Preferential use of a single pool, variable volume model for calculating urea distribution and removal during hemodialysis at least once per month;

2. Quantification of urea removal during a single dialysis session using formal urea kinetic modeling for adults and children;

3. Prescription of a Kt/V of 1.3, so that the minimum delivered Kt/V would be 1.2;

4. Routine baseline measurement of a hemodialyzer’s TCV prior to the first use and prior to each subsequent use;

5. Discarding of a hemodialyzer if its TCV is less than 80% of the original value; and

6. Vigorous effort to ensure patient comfort during hemodialysis by using strategies to minimize cramps and hypotension.

In the years since the RPA and NKF-DOQI recommended how the delivered dose of hemodialysis should be measured and clarified the minimum acceptable dose of hemodialysis, a significant improvement in reported dialysis dose has been reported in the United States.29-31 In 1993, a population-based cohort study of 13,500 adult ESRD patients noted that only 36% of the patients received a urea reduction ratio (URR) of 65%.19 U.S. News and World Reports described this state of care as "deadly dialysis."79 These findings were confirmed and extended by the ESRD Core Indicators Project, a nationwide quality improvement project, and conducted by the Health Care Financing Administration (HCFA) using the ESRD Networks. A random national sample of adult, ESRD patients from October to December 1993 showed that only 43% of the patients had a URR 65%; the mean URR was 62.7%.31 The greatest deficiency in URR was observed for blacks, who had a 60% greater likelihood of receiving an inadequate dialysis dose compared with whites.80 From 1993 to 1997, the mean URR increased from 62.7% to 68.0%.31 Improvement of a similar magnitude was observed in another national data set; the median URR increased from 58.9% 9.8% to 69.5% 8.75% from 1990 to 1997, respectively.29 The percentage of patients receiving a benchmark URR 65% increased from 43% in 1993 to 72% in 1997. The most dramatic improvement in dialysis dose was achieved by blacks, for whom a 92% increase in the number receiving a URR 65% was achieved.31,80 In contrast, there was a 59% increase in the number of whites receiving a URR 65%. As a result, the racial disparity in dialysis dose has narrowed. The odds ratio of achieving an inadequate dialysis dose for blacks compared with whites has declined from 1.6 in 1993 to 1.2 in 1997. Several data sets have demonstrated that the dose of dialysis varies inversely by weight, total body water, body surface area, and body mass index.55,57,81 In that all these anthropometric parameters are greater on average in blacks with ESRD than whites, and fixed dialysis doses are prescribed, it may not be inappropriate that the average dialysis dose is lower in blacks than in whites. Patient and/or nephrologist behaviors also seem to be contributing factors.55 Thus, the increment in dialysis dose for blacks is all the more significant, since it occurred in the setting of unfavorable anthropometric attributes and treatment compliance for improvement. Blacks with ESRD have greater urea distribution volumes than whites and are more likely to terminate hemodialysis prematurely. If dialysis care teams are offered advice regarding "best" clinical practices, as provided by the RPA and NKF-DOQI’s clinical practice guidelines, quality of care can be improved. Translation of some of the NKF-DOQI clinical practice guidelines into national clinical performance measures (CPM) may be helpful.82 The national HD adequacy CPM initiative will provide some insights into the potential impact of NKF-DOQI guidelines on hemodialysis adequacy.

Despite these improvements in patient care, many opportunities for significant improvement remain. Firstly, more than 20% of the ESRD patients in the 1996 Core Indicators Project received a Kt/V less than 1.2.31 Secondly, procedural problems persist with the sampling method used for obtaining the predialysis and postdialysis blood samples to measure the BUN concentration. Using spline techniques to determine the dialysis dose at which optimal mortality benefit is conferred, a recent analysis suggests that inappropriate timing/technique for acquisition of the postdialysis BUN samples is so prevalent that the potential mortality benefit associated with the apparent increase in dialysis dose may be minimal.63

Because many ESRD patients still do not receive an adequate dose of hemodialysis, and the literature suppporting the NKF-DOQI HD Adequacy Guidelines has expanded, the HD Adequacy Work Group has reevaluated the topics addressed in the previous clinical practice guidelines. The NKF-KDOQI HD Adequacy Work Group focused its efforts on a review of the existing Clinical Practice Guideline on Hemodialysis Adequacy and a discussion of operational and clinical issues that may affect the practical acceptance and/or implementation of the RPA and DOQI hemodialysis adequacy guidelines. Three specific Work Group objectives were defined:

1. Review the NKF-DOQI Clinical Practice Guideline on Adequacy of Hemodialysis. Based upon this review, develop updates and supplements as needed.

2. Identify barriers to the acceptance and implementation of the NKF-DOQI guidelines for hemodialysis adequacy.

3. Develop strategies for enhancing the implementation of the NKF-DOQI clinical practice guidelines for hemodialysis adequacy.


Flux of Large Molecular Weight Solutes

The HD Adequacy Work Group recognizes that the clearance of a marker solute, such as urea,45,83 is only one of the many parameters that define or are relevant to the global concept of hemodialysis adequacy. Another parameter is membrane flux of larger molecular weight solutes. For example, the use of hemodialysis membranes that have relatively higher clearances for larger molecular weight solutes, such as vitamin B12 and β2-microglobulin (molecular weight of 1,355 and 12,500 daltons, respectively), may reduce the likelihood of developing dialysis-associated amyloidosis,84-89 decrease the severity of lipid abnormalities in ESRD patients,90 and improve survival.87-89,91 However, because of the clinical impact of persistent deficiencies in the delivered dose of hemodialysis based on urea clearance, a limited literature on the association between patient outcomes and membrane flux, and limited time and resources, the HD Adequacy Work Group focused on the clearance of the more conventional marker solute–urea. The Work Group did not address membrane flux. The ongoing National Institutes of Health HEMO Study, a prospective, randomized intervention trial, will evaluate the effect of membrane flux on morbidity and mortality in hemodialysis patients.49,92

Membrane Biocompatibility

Independent of the delivered dose of hemodialysis as measured by urea clearance, hemodialyzers composed of selected membrane materials may interact with the effector limb of adaptive immunity.93,94 Described as membrane biocompatibility, interactions between soluble and cellular components of the blood and selected dialysis membrane materials result in perturbations in the complement cascade95-99 and granulocyte number and function.100-102 As a consequence of these membrane-associated immunologic abnormalities, ESRD patients may be at increased risk of malnutrition, infection, hospitalization, and death.93,94,103-107 Because of the extensive scope of this topic, resource limitations, and the focus of the Work Group on small molecular weight solute clearance, membrane biocompatibility was excluded from the literature review.

Appropriate Timing for Initiation of Hemodialysis

Delaying the initiation of dialysis until frank uremia develops is clearly deleterious to the patient’s physical and psychological well-being.108 For patients with less severe degrees of advanced kidney failure (glomerular filtration rate [GFR], 10 to 20 mL/min), the benefit of relatively early dialysis is less clear, however. The HD Adequacy Work Group recognizes that patients who are initiated on hemodialysis relatively early will have greater residual kidney function that will enhance small and large solute clearance over that provided by dialysis alone. However, the Work Group did not undertake a full literature review in an attempt to define an optimal time or clinical setting for the initiation of maintenance hemodialysis because:

1. The preponderance of outcome studies of the impact of hemodialysis dose has excluded patients with residual kidney function or assumed that none was present.

2. Few outcome analyses have been reported that examine the relationship between residual kidney function and mortality/morbidity on maintenance hemodialysis.

3. Residual kidney function declines with increasing vintage on hemodialysis, making it an unstable influence on the delivered dose of dialysis.

4. The Work Group elected to focus resources on the fundamental issue of the impact of small molecular solute clearance on patient outcomes once hemodialysis is initiated.

For dialysis care teams who seek direction on appropriate timing for initiation of dialysis, the NKF-KDOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy provide guidance.109

Hemodialysis Dose and Nutrition

Another topic not reviewed by the HD Adequacy Work Group is the relationship between hemodialysis dose and nutrition. Some investigators have suggested that the dose of hemodialysis and/or the composition of the hemodialyzer membrane affect a patient’s dietary protein intake, as measured by the normalized protein catabolic rate.110,111 This and other issues related to nutrition in kidney disease patients are addressed in the NKF-KDOQI Nutrition Guidelines.112

Quality of Life and Rehabilitation

Although the HD Adequacy Work Group recognizes the importance of the patients’ perception of their quality of life as an outcome measurement,113,114 this topic was not reviewed. The connection between rehabilitation and adequacy of hemodialysis is likewise important. Adequacy of dialysis is crucial for success in any of these areas. However, the Work Group elected to focus resources on the fundamental issue of the impact of small molecular weight solute clearance on the principal patient outcome of mortality.


These guidelines apply to all adult and pediatric hemodialysis patients with ESRD and negligible kidney function (GFR <5 mL/min) who receive outpatient hemodialysis three times per week. These guidelines are not applicable to patients who undergo hemodialysis less than or greater than three times per week, hospitalized patients receiving hemodialysis, patients with a residual GFR 5 mL/min, or patients with a reasonable presumption of recovery of kidney function. The guidelines also may not be applicable to hemodialysis patients outside of the United States and the American Trust Territories (Puerto Rico, Guam, American Samoa, and Saipan) because of substantial international differences in patient mix, processes of patient care, and reimbursement mechanisms for the care of ESRD patients.


These guidelines are based on evidence in the published literature and, where evidence is not available, on consensus opinion of the HD Adequacy Work Group based on the available literature. For each guideline, there is a notation of whether the guideline is based on evidence or opinion. It is the intent of the HD Adequacy Work Group that the material provided herein be used solely as recommendations for patient care and not as standards. However, it is the duty of the dialysis patient care team to consider implementing these recommendations on an individual patient basis and, where they are not or cannot be applied, to strive to optimize patient care by offering reasonable and safe alternative processes of care. Furthermore, the Work Group acknowledges its awareness of the financial ramifications of these guideline statements for the providers of hemodialysis care. Successful implementation of the Clinical Practice Guidelines for Hemodialysis Adequacy will also depend on payers providing adequate reimbursement for high quality patient care, including the appropriate use of laboratory-based performance measures and requisite dialysis supplies and equipment.

* To obtain a copy of the RPA guideline, see ordering information in Appendix A.

© 2001 by the National Kidney Foundation, Inc.







© 2001 National Kidney Foundation, Inc

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