Clinical Practice Guidelines and Clinical Practice Recommendations
2006 Updates
Hemodialysis Adequacy
Peritoneal Dialysis Adequacy
Vascular Access



Research recommendations have been grouped into 3 categories: critical research, important research, and research of interest. These rankings were made by the Work Group based on current evidence and the need for research to provide additional evidence for the current CPGs and CPRs. No attempt was made to rank research recommendations within each of the 3 research categories.

Guideline 1: Initiation of HD
It has been well shown that education and planning for kidney failure can improve patient outcomes, but optimal approaches have not been established. Answers to certain questions could help improve clinical outcomes while reducing costs. These questions include the approaches to education and planning for kidney failure in different demographic and cultural groups and their relative costs. How effective are video and internet-based educational materials? Are computer-interactive programs helpful? How can nephrologists, nurses, social workers, dietitians, pharmacists, other professionals, and patient volunteers work together most effectively to educate new kidney patients and families? What is the best training for kidney patient educators? How much of the educational role should nephrologists delegate? For example, can earlier teaching about dietary potassium allow more extensive treatment with ACE inhibitors and ARBs in patients with CKD? Can new approaches to early dietary education yield improved volume and phosphorus control when patients reach kidney failure? What are the psychological and behavioral consequences of early education about the prospect of eventual organ failure and the shortened life expectancy associated with kidney failure?

Estimation equations for GFR (Table 1, Guideline 1) should be examined in patients who produce unusually little creatinine, in particular, the elderly and patients with other chronic illnesses. A second important clinical group for which current estimating equations have not been validated is those with significantly decreased kidney perfusion, as occurs in patients with advanced heart failure.

Studies of the time to initiate replacement therapy are needed to determine the consequences of timing on survival, morbidity, and cost. Results of the IDEAL Study will be critical, but it seems unlikely to be definitive for all clinical subgroups. In view of racial differences in dialysis mortality rates, it seems plausible that response to early treatment might vary by race. The HEMO Study finding of differential dose effects in women also suggests the possibility that the response to early initiation also might vary by sex. Because of longer exposure to uremia, do patients with a slower decrease in GFR benefit from earlier initiation of kidney replacement therapy? Do patients with primary tubular disorders benefit from initiation of KRT at a higher level of GFR than patients with primary glomerular disorders? These questions should be addressed in particular groups of interest, including children and the elderly.

Guideline 2: Methods for Measuring and Expressing HD Dose
The ongoing Frequent HD Network will provide data that should be used to evaluate potential benefits of short-daily or nocturnal dialysis. If published uncontrolled studies showing better QOL are confirmed, efforts must be directed to provide more frequent dialysis in a less encumbering manner.

The conductivity method promises to eliminate the need for drawing blood before and after dialysis and can be applied to each dialysis treatment. Objective studies are needed to correlate the delivered dose measured by using conductivity (ionic) dialysate methods with both eKt/V and spKt/V determined by using classic blood-based methods. Testing is needed to show whether this method is a reliable substitute for the present technique.

Guideline 3: Methods for Postdialysis Blood Sampling
Because the amount of blood drawn from dialysis patients should always be minimized, it is desirable to minimize the volume of the discard sample when drawing blood from a venous catheter. Studies of how the ratio of discarded volume to catheter lumen volume affects BUN concentration would be of practical interest.
Because timing may be different in smaller patients with shorter circuit pathways, validation of the stop-blood-flow method and stop-dialysate-flow method for determining dialysis dose in children requires future research.

Guideline 4: Minimally Adequate HD
There are no reliable data regarding mortality that are not extremely susceptible to patient selection, and no RCT comparing mortality rates is foreseen in the near future. Whether more frequent dialysis reduces hospitalization rates may be answered by an RCT currently in progress (NIH Frequent HD Network trial), although this trial is underpowered to detect other than a very large reduction. However, it is powered to detect improvements in both QOL measures and left ventricular mass index; the latter is strongly related to “hard” cardiovascular outcomes.

An alternative measure of dialysis dose in units measuring conductivity is Kecn × T/Vant, where Kecn is the conductivity-derived dialyzer clearance, T = session length, and Vant = anthropometric volume. Studies are needed to determine whether adequacy determined serially using a conductivity standard is more or less variable, and more or less reliable, than adequacy determined based on classical urea kinetics with predialysis vs. postdialysis BUN measurements. Studies are also needed to determine whether much of the same information gleaned from monthly pre- and postdialysis BUN measurements in terms of PCR could be obtained using monthly predialysis BUN measurements only, and quarterly pre/post BUN values.

Further study would look at the ratio of modeled to anthropometric volume, both cross-sectionally, and serially in large numbers of patients, and the possibility of dosing dialysis based on Kecn× T/BSA, where BSA is body surface area multiplied by a correction factor such that it would vary to the 2/3 power and in effect, reflect dosing based on body surface area.

Guideline 5: Volume and Blood Pressure Control
The cost of dialyzer and blood tubing disposal has a direct impact on reuse, which reduces this provider burden. Aside from the biological hazard, recycling of dialyzer and tubing materials could reduce the requirement for disposal site space. Studies of the potential economic benefits are needed.

Reuse of dialyzers and blood tubing may influence patient exposure to spallated particles, plasticizers, bore fluid, ethylene oxide, and other noxious manufacturing residuals from newly manufactured dialyzers. Studies should compare these exposures with the single-use situation when dialyzers and tubing are reused.

Guideline 6: Preservation of RKF
Additional comparative studies of outcome in patients with and without RKF are needed.355 At the present time, many dialysis clinics do not measure RKF routinely and some do not measure it at all. Such studies would help resolve the critical question about the importance of RKF measurements. Perhaps even more helpful would be a controlled clinical trial in which the prescribed dialysis dose is adjusted or not in patients with significant RKF.

Some studies have implicated contamination of the water used to prepare dialysate as a cause of dialysis morbidity and mortality. Other studies suggested that ultrapure dialysate helps preserve RKF.232 Additional confirmatory studies are needed to determine whether introduction of ultrapure dialysate into routine clinical practice would help preserve RKF and improve such clinical outcomes as blood pressure control, nutritional status, and QOL.

A trial of ACE inhibitors or ARBs should be done to evaluate the effectiveness of such agents in preserving RKF.
After dialysis therapy has started, diuretics often are prescribed for patients with good urine output to help with potassium balance and avoid excessive fluctuations in ECF volume and blood pressure. This practice may or may not help preserve RKF. Studies should address the effectiveness of various diuretic doses and whether diuretics should be advocated in patients with significant urine output to help preserve RKF.

For patients in whom the targeted prescribed dialysis dose is based on RKF, there is an obvious need to measure RKF, but the optimum frequency of measurements has not been determined. The optimum frequency may depend on the type of kidney disease and the patient's history of its progression.

Guideline 7: Clinical Outcome Goals
Additional studies are needed to validate the tools currently used to measure QOL and patient satisfaction within the diverse CKD stage 5 population. Interventions used to improve QOL and patient satisfaction should be evaluated to determine success in improving QOL, patient satisfaction, and clinical outcome. As standards of care are modified and new care strategies are introduced, there is need for periodic reassessment of the presently recommended dose of dialysis and its effect on patient mortality, hospitalization rates, QOL, patient satisfaction, and transplantation rates.

Guideline 8: Pediatric HD Prescription and Adequacy
The high rates of young adult HD patient cardiovascular mortality and morbidity,356,357 psychological illness, and unemployment358 compel pediatric HD patient study in the areas of inflammation, cardiovascular fitness, nutrition assessment and malnutrition treatment, and health-related QOL. Because many young adult patients are treated in pediatric programs and have the potential to develop morbidities in their pediatric years, there is a need to study these areas in pediatric patients. Measurement of HD small-solute clearance, preferably using either measured or validated estimated eKt/V, and nutrition, using nPCR, are critical to control for the dose of delivered dialysis and nutrition status in any pediatric HD outcome study. Recent recommendations from the European Pediatric Dialysis Working Group359 provide an excellent basis in terms of the current state of the art in pediatric HD practice, from which future research should emanate to improve the care of pediatric HD patients.

Guideline 1: Initiation of HD
Less critical questions include measurement of patients' preferences (in the technical sense of utility) for the states of education vs. ignorance regarding prognosis and choices. It also would be important to understand demographic and cultural determinants of preference variation. Finally, work is needed on the ethical implications of therapeutic attempts to influence patient preferences. These issues are all less critical as research priorities, not because they are less important, but because the findings are less likely to influence practice and policy in the short term.

Guideline 2: Methods for Measuring and Expressing the HD Dose
Tests of variance are needed for Kt/V measured in patients receiving daily dialysis treatments. Theoretically, the variance will be larger because measured BUN values will be considerably lower and excursions from predialysis BUN to postdialysis BUN also will be lower, which reduces the power of kinetic modeling. How much lower and how much variance have not been determined in an experimental setting. This study can be done simply by drawing predialysis and postdialysis blood samples several days in succession. If blood-based measurements of Kt/V are found to be less reliable in these patients, dialysate methods may be required to measure the delivered dose. However, dialysate methods are intrinsically less accurate for measuring Kt/V than blood-based methods,364 so additional comparative studies will be required if the blood-based methods are found to be inadequate.

Guideline 3: Methods for Postdialysis Blood Sampling
A study of needlestick injuries in dialysis clinics might help promote the use of blood-sampling procedures that do not involve use of exposed needles. This is an area of obvious importance and interest for which very few data are available.

Guideline 5: Volume and Blood Pressure Control
More research should be devoted to reprocessing techniques for various types of dialyzer membranes made by different manufacturers, especially with regard to approaches involving heat and more biocompatible chemicals, such as citric acid.

Guideline 6: Preservation of RKF
Observational studies should include data to determine whether RKF serves to reduce fluctuations in serum potassium and bicarbonate concentrations and reduce ECF volume and blood pressure fluctuations.

Some patients with slowly progressive kidney disease might benefit from incremental dialysis frequency (initiation of HD at a frequency < 3 times per week). Studies are needed to determine whether such a practice would help preserve RKF in patients with significant urine output and those with a marginally functional renal allograft.

RKF imparts a stronger survival advantage than dose of dialysis. Investigations should explore potential kidney synthetic functions that, if preserved in the remnant kidney, may provide survival benefits not explained by level of GFR.

Guideline 7: Clinical Outcome Goals
There is a need for analysis of data linking clinical outcomes to recommended processes within the target goals. This would include analysis of the impact of specific KDOQI processes adjusting for established factors (eg, blood pressure control, hemoglobin A1c [HbA1c], lipid management, pharmacological therapy) that strongly influence clinical outcomes of HD patients. Periodically, there is a need for refining case-mix adjustments over time to reflect changes in relative contribution of traditional, nontraditional, and emerging risk factors as standards of care change.

Guideline 8: Pediatric HD Prescription and Adequacy
Recent data from a small pediatric study showed benefits of daily nocturnal HD in children. Additional study of daily HD treatment schedules and technologies should be undertaken in children.

Less critical issues include the development of prediction instruments to allow estimation of time to symptomatic kidney failure on the basis of serial GFR estimates.

Less critical questions include measurement of patient preferences about the tradeoffs between the burdens and benefits of earlier therapy.

Investigation of dialysis creatinine kinetics would help assess the effect of muscle mass on outcome and compare somatic with visceral body mass as risk factors for survival.

Studies of large patient populations to correlate urine output with RKF would help determine whether urine volume-related cutoff values for ignoring RKF are useful.

Although the potential insults listed in CPR Table 16 are known to injure normal and partially damaged native kidneys, studies are required to indict each insult in patients with CKD stage 5. It is unlikely that controlled clinical trials will appear in the near future; therefore, observational studies are encouraged.

The benefits of RKF may relate more to renal mass than urine volume. This possibility should be considered in outcome studies. Also, it would be helpful to correlate kidney size with RKF to determine whether RKF is predictable based on size.