2010 uptodate adequacy dp

Official reprint from UpToDate® www.uptodate.com

©2010 UpToDate®

Authors

John M Burkart, MD

William L Henrich, MD, MACP

Section Editor

Thomas A Golper, MD

Deputy Editor

Theodore W Post, MD

Adequacy of peritoneal dialysis

Last literature review version 18.1: Janeiro 2010 | This topic last updated: Janeiro 29, 2010

INTRODUCTION — The optimal method to assess the adequacy of peritoneal dialysis (PD) therapies

(both of continuous ambulatory PD (CAPD) automated or automated peritoneal dialysis (APD)), as

with hemodialysis therapies, is controversial [1]. Liberal clinical criteria for adequate dialysis include a

feeling of well-being, the absence of uremic symptoms, and reasonable control of biochemical

parameters. However, many of these are subjective, and often minimized by the patient. On the other

hand, the presence of uremic symptoms (such as nausea, vomiting, or chest pain from pericarditis) or

rising BUN and plasma creatinine concentrations provide clear evidence of uremic symptoms or

insufficient clearance of uremic toxins. Other methods to quantify the adequacy of dialysis include

laboratory measurements of solute clearance using urea or creatinine kinetics.

Historical observational studies suggested that more solute clearance would improve patient well

being and relative risk of death. As a result, guidelines such as those from the National Kidney

Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) recommended a weekly total solute

removal in terms of Kt/Vurea for CAPD of greater than 2.1 per week [2]. Due in part to increased

awareness of the link between adverse outcome and inadequate dialysis, and national guidelines such

as the KDOQI guidelines mentioned above, epidemiologic data suggest that the average peritoneal

dialysis dose delivered to patients in the United States has increased to a stable level over the last

several years [3-6]. In 2007, over 93 percent of all patients undergoing CAPD in the United States

had a mean weekly Kt/V of greater than 1.7 [6]. Because of this emphasis on achieving higher

dialysis doses, transfer to hemodialysis because of inability to achieve that Kt/Vurea target or what

was clinically thought to be "inadequate" dialysis with PD was noted to occur [7,8], perhaps at times

when it was not needed on a clinical basis.

These higher solute clearances (weekly Kt/V >2.1), however, may not have been necessary. Evidence

has emerged that lower weekly solute clearances are associated with similar survival rates. In

addition, when the dose of dialysis is increased to achieve higher target values, there is always the

potential for the introduction of adverse effects associated with efforts to enhance the dose. This may

include hernias from the increased intraabdominal pressure due to larger volumes of dialysis solution

infusion, patient dissatisfaction because of the increased time needed to perform exchanges, weight

gain and other metabolic consequences from higher glucose exposure and absorption, possible

systemic toxicity from any components of the PD solution that may be absorbed (glucose degradation

products), and a higher cost to society for the additional dialysis solutions. These effects may be

minimized with the new weekly solute clearance targets discussed in this topic review.

The determinants of and the methods used for the assessment of peritoneal dialysis adequacy will be

reviewed here. These methods have largely been confined to estimates of solute clearance, due in

part to the correlation between solute clearance and patient outcome.

However, it is acknowledged that the signs and symptoms of uremia are related to all the retained

solutes and loss of metabolic control that results from loss of renal function. Inadequate ultrafiltration

Adequacy of peritoneal dialysis http://www.uptodate.com/online/content/topic.do?topicKey=dialysis/56...

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may also contribute to adverse outcomes [9-12].

SOLUTE CLEARANCE — A BUN level below 100 mg/dL (36 mmol/L) and a plasma creatinine

concentration below 18 mg/dL (1584 µmol/L) were, in the past, considered to represent adequate

biochemical treatment in PD [13]. Subsequently, calculations of a weekly Kt/V for urea (Kt/Vurea)

and a weekly creatinine clearance (CCr) were proposed as more objective criteria for adequacy.

Kt/Vurea and creatinine clearance — Adequate dialysis was originally defined by some

investigators as a weekly Kt/Vurea exceeding 1.7; lower values were considered inadequate, often

being associated with increasing symptoms, hypoalbuminemia (a marker for malnutrition), and a

protein catabolic rate below 0.9 g/kg per day (an index of decreased protein intake that was

presumably due to diminished appetite) [14-16]. (See "Protein catabolic rate in maintenance

dialysis".)

These observations were primarily based upon anecdotal clinical experience and cross-sectional data

suggesting that both hypoalbuminemia and lower weekly Kt/Vurea levels were associated with

increased mortality in patients treated with PD (graph 1) [14]. (See "Patient survival and

maintenance dialysis".)

CANUSA study — The hypothesis that a lower weekly Kt/Vurea level is associated with increased

mortality was supported in a prospective, cohort, multicenter observational study in Canada and the

United States (CANUSA) [17]; this study evaluated the relationship of the adequacy of dialysis and

nutritional status to mortality, morbidity, and technique failure. The following results were obtained:

A decrease of 0.1 unit in total (peritoneal and residual renal) Kt/Vurea was associated with a 5

percent increase in the relative risk of death (graph 2).

A decrease in total (peritoneal and corrected residual renal) weekly creatinine clearance of 5

L/1.73 m2 body surface area was associated with a 7 percent increase in the relative risk of death

(graph 3).

A decrease in creatinine clearance was associated with an increase in the relative risk of technique

failure and incidence of hospitalization.

A Kt/Vurea of 2.1 and a weekly creatinine clearance of 70 L/1.73 m2 body surface area were both

associated with a 78 percent expected two year survival rate.

These predicted survival results were based upon total clearance values and two important

assumptions:

Total clearance remains constant

1 unit of peritoneal clearance equals 1 unit of residual renal clearance

However, in a reanalysis of this study, survival was largely related to residual renal function (which

changed over time) and not to peritoneal clearance alone (which did not change) [18]. Findings

consistent with this observation were reported in some subsequent observational studies [19,20]. In a

report of nearly 2700 patients, for example, each mL per minute increase in the renal creatinine

clearance, but not the clearance obtained with peritoneal dialysis, was associated with a 12 percent

reduction in the odds ratio for death [19].

We therefore recommend measures aimed at preserving residual renal function among peritoneal

dialysis patients.

ADEMEX and Hong Kong trials — Subsequent to the CANUSA study, two prospective

randomized controlled clinical trials evaluated the relationship of various levels of small solute

clearance on the relative risk of death. These trials, referred to as the ADEMEX and Hong Kong


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studies, support the concept that the minimally acceptable delivered small solute clearance for

patients on PD is less than what was previously recommended. These trials are reviewed in this

section.

The ADEMEX trial was a prospective randomized trial conducted in Mexico that compared two levels of

dialysis dose [21]. In this prospective study, 965 patients were randomly assigned to either

continuation of their usual dialysis prescription (four daily 2 liter exchanges) or an increase in dose to

maintain a creatinine clearance of greater than 60 liters/week per 1.73 m2. Initial clearance values

and demographic variables were the same in both groups. Body mass index (BMI) was similar in the

two groups (25.3 and 25.8 kg/m2 respectively). The intervention was confined to the higher dialysis

dose group, with the control group actually being an observational cohort (ie, patients were not

randomized to a lower dose of dialysis but rather continued on their pre-study "standard" dose of

dialysis). As with the HEMO trial, this study did not definitively establish a lower limit of total solute

clearance.

Patients were followed for a minimum of two years, unless they were transplanted or died. During this

period, peritoneal creatinine clearance values and Kt/Vurea remained the same for the control group

(46 liters/week per 1.73 m2 and 1.62, respectively), and by study design, markedly increased in the

intervention group (57 liters/week per 1.73 m2 and 2.13, respectively). At study end, there was no

difference in overall patient survival between the two groups (68 and 69 percent); these overall

mortality rates are similar to those observed in the United States and similar to the two year survival

observed in the HEMO trial. (See "Kt/V and the adequacy of hemodialysis", section on 'HEMO study'.)

Approximately 50 percent of patients in each group were anuric. In a subgroup analysis of these

patients, there was also no difference in survival between groups assigned to either dose [22]. In

addition, there was no difference in quality of life, despite quality of life predicting outcome.

In the study from Hong Kong, 320 new CAPD patients were randomly assigned to a target Kt/Vurea of

1.5 to 1.7, 1.7 to 2.0, or greater than 2.0 [23]. All patients had to have a residual renal Kt/V of <1.0

to be randomized. Average body mass index was 22 kg/m2, smaller than that of patients in the

ADEMEX study. Although there was no difference among the three groups in survival, serum albumin

levels, and hospitalization rates, patients assigned to a dialysis dose of less than 1.7 required higher

doses of erythropoietin and had more uremic symptoms than those in the other two groups.

In contrast to the ADEMEX trial in which the control group continued on the baseline prescription (no

intervention), there was an attempt in the Hong Kong trial to maintain Kt/Vurea between 1.5 and 1.7.

During the study, some patients who were randomized to that dialysis dose actually had their baseline

PD prescription decreased. However, separation between groups was not achieved until almost one

year into the study; thus, follow-up for patients in the "lowest randomized dose" at the target level

was only short term. No one was randomized to a dose with a weekly Kt/V < 1.5/week. Therefore, the

"minimal" dose of adequate dialysis was not firmly established.

A similar lack of survival benefit with increased dialysis has been observed in multiple additional

observational studies [24-27]. In a prospective observational study from the Netherlands, the

correlation between peritoneal solute clearance and survival was evaluated among 130 anuric

patients undergoing PD, of whom 102 were being administered CAPD [26]. A significant increase in

the relative risk of death was only associated with very low levels of dialysis: a Kt/Vurea <1.5 per

week and a creatinine clearance <40 L/week/1.73 m2.

2006 K/DOQI guidelines — Findings from ADEMEX, the Hong Kong trial, and other studies

provide support for the establishment of a lower delivered weekly Kt/V in the range of 1.7 or 1.8 per

week [28]. The two randomized controlled studies were the principal data used to formulate the

recommendations for the 2006 K/DOQI guidelines [29].


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The 2006 K/DOQI work group recommend the following:

For patients with residual kidney function (RKF) (arbitrarily considered to be significant if urine

volume is >100 mL/day):

- The minimal delivered dose of small solute clearance should be a total (PD and RKF) Kt/Vurea of

at least 1.7/week. The total solute clearance (PD and RKF) in terms of Kt/V urea should be measured

within the first month of PD and, subsequently, at least once every four months. A 24 hour urine

collection for urine volume and solute clearance should be obtained, at a minimum, every 2 months.

(See "Patient information: Collection of a 24-hour urine specimen".)

For patients without RKF (considered insignificant if urine volume is <100 mL/day):

- The minimal delivered dose of small solute clearance should be a peritoneal Kt/Vurea of at least

1.7/week. The dose should be measured within the first month of starting dialysis and, subsequently,

at least every four months.

Consistent with this view are the 2005 European Best Practices Guidelines and the 2006 International

Society for Peritoneal Dialysis (ISPD) Guidelines/Recommendations, which suggest a minimum weekly

target Kt/Vurea of 1.7 [30,31]. We also recommend that the minimal delivered total solute clearance

of Kt/Vurea should be at least 1.7/week for all patients undergoing peritoneal dialysis

There are some cautions that must be mentioned when reviewing the new K/DOQI guidelines. First, in

contrast to prior guidelines where a target dose was recommended (so that if delivered dose is less

than targeted dose the patient would still be in a safe dose range and unlikely to have severe uremic

symptoms), these guidelines recommend a minimal delivered dose stating that everyone should be

above this minimum at all times.

However, this does not preclude each dialysis center from establishing its own target level to ensure

the delivered dose is above the K/DOQI minimal dose. Since the actual delivered dose is frequently

below that which is prescribed, the clinician should consider prescribing an optimal dose that, when

delivered, provides a dialysis dose above a basic minimal threshold level to practically all patients. In

contrast, one could prescribe an adequate target dialysis dose (such as a Kt/V of 1.7/week),

recognizing that the delivered dialysis dose would likely frequently fall below the target level in a

subgroup of patients. At our unit, we prescribe a target dose that is sufficiently above the minimum

threshold level so that all patients are likely to always receive such minimal values. Our target is a

Kt/Vurea of 1.8/week.

A second caution is that the patients in Mexico and Honk Kong tended to be smaller and in general

have lower dietary protein intakes than observed in the United States. It is acknowledged that dialysis

adequacy includes more than small solute clearance, with metabolic control also being significant. If a

patient is eating significantly more protein than the patients in those two studies, they may need a

higher solute clearance rate or dose of dialysis to prevent acidosis and uremic symptoms related to

protein metabolism. Although the ADEMEX and Honk Kong studies did not find a spontaneous increase

in protein intake in patients randomly assigned to the higher dialysis doses, this does not imply that

some patients would not need higher doses of dialysis to maintain metabolic control.

Third, if residual renal function is included in total solute clearance measurements, it is important to

get follow up values of residual renal clearance every two months. The clinician should be prepared to

increase the peritoneal component if there is a decrease in the residual kidney portion. This is

especially true if the total solute clearance is only minimally above the minimal threshold and a

significant portion of the total is due to residual kidney function. There is marked variability in the


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measured 24 hour clearance from day to day (perhaps due to difficulty in accurately collecting a 24

hour volume in a patient with advanced chronic kidney disease) and residual renal function is likely to

decrease over time, especially if the patient is exposed to any nephrotoxins.

Overall, there is a paucity of data to prove that replacing lost residual renal clearance with increased

peritoneal clearance will give the predicted results in terms of relative risk of death. Nevertheless,

there is a general consensus that such a relationship in part exists and that total small solute

clearance must be kept above a certain minimum amount to optimize outcomes, patient well being

and longevity. In fact, in the Hong Kong and the ADEMEX study, the peritoneal prescription was

altered as residual kidney function decreased to maintain target weekly total solute clearance goals.

As noted above, historically, most investigators agreed that either urea or creatinine kinetics could be

used as a yardstick for adequate PD. As a result, it was recommended that calculation of both the

weekly Kt/Vurea and the peritoneal creatinine clearance should be used to assess dialysis adequacy.

It was therefore proposed that adequate dialysis required either a total weekly Kt/V of >2.0, and/or a

total weekly creatinine clearance of at least 60 L per week per 1.73 m2 body surface area

[15,17,32,33].

In contrast, the 2006 NKF-KDOQI guidelines recommend using only Kt/V urea as the "yardstick" for

dialysis dose and see no additional benefit to using both Kt/Vurea and creatinine clearance to monitor

dialysis dose. They therefore recommend that a total solute clearance target should only be in terms

of Kt/Vurea. However, in the text and in the clinical practice recommendation section, it is noted that

knowledge of weekly creatinine clearance may be helpful for other reasons:

24 hour creatinine excretion is a surrogate for creatinine generation and hence muscle mass. A

decreasing value would suggest muscle loss either as a result of malnutrition, disuse, surgical

amputation, or aging. Sequential measurements may be an additional parameter to monitor. (See

"Patient information: Collection of a 24-hour urine specimen".)

Optimizing creatinine clearance would also promote increased phosphate removal, since phosphate

clearance tends to parallel that of creatinine.

Maneuvers that increase urea clearance may not necessarily result in an increase in creatinine

clearance and other molecules of the same or larger molecular weight. (See "Why Kt/V and creatinine

clearance may not correlate in continuous peritoneal dialysis".) In general, if one wants to monitor

both, we recommend that threshold Kt/Vurea values should be met when there are discrepant values.

Automated peritoneal dialysis — There are no prospective randomized trials that have looked at

relative risk of death in relationship to dose in automated peritoneal dialysis (APD) patients only.

Prior guidelines for an increase in dose were opinion-based and were extrapolations from Kt/V studies

in hemodialysis patients.

There is a current consensus that this previous extrapolation is not indicated. This is because

mortality outcomes in the HEMO trial and the ADEMEX trial were similar, approximately 70 percent

survival at two years, despite markedly differences in attained Kt/V in the two trials. (See "Kt/V and

the adequacy of hemodialysis".)

We therefore agree with the 2006 K/DOQI work group that higher targets are not required with APD

[29]. We suggest that the minimal dose of Kt/Vurea should be 1.7/week for those undergoing APD.

Although not a part of the NKF-DOQI 2006 guidelines, in order to minimize lack of clearance of larger

solutes, the 2006 ISPD guidelines also suggest that in addition to weekly Kt/Vurea targets, given the

variable relationship between urea and creatinine clearance, one should consider an additional CCr

target of 45 L/week per 1.73 m2 for APD [31].


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Another caveat for APD is that, once the patient is anuric or with minimal urine volume, the patient

should undergo 24 hours/day of PD to optimize middle molecular weight solute clearance, as

randomized trials have only evaluated patients undergoing 24 hours/day of PD.

Peritoneal membrane transport — Although solute clearance is a significant controllable factor

underlying mortality in all dialysis patients, survival among PD patients is also due to a complex

interplay among other characteristics. These include, but are not limited to, age, comorbid conditions,

presence of diabetes, country in which patient is getting their dialysis, adherence to the prescription,

control of other ESRD related parameters such as blood pressure, calcium-phosphate metabolism, and

anemia. Historical observational data suggested that survival on PD was also related to individual

peritoneal membrane transport characteristics [34]. However, more contemporary data do not

support those observational findings, and most investigators feel that there is no survival advantage

based on transport type if PD is properly prescribed [35,36]. (See "Patient survival and maintenance

dialysis".)

The historical observation on survival and peritoneal transport was first evaluated using the Cox

proportional hazards method in a follow-up evaluation of the cohort enrolled in the CANUSA

prospective study [37]. Increased peritoneal transport was associated with significantly lower survival

rates:

At two years, patient survival probabilities were 91, 80, 72, and 71 percent for low, low average,

high average, and high transporters, respectively (p = 0.11).

When creatinine clearance or Kt/Vurea were utilized as estimates of dialysis adequacy, the

relative risk of death was 1.0, 1.6, 2.3, and 2.0 for the different transport categories.

Thus, after controlling for delivered dose, low and low average transporters had higher survival rates

than high average and high transporters, suggesting that subsets of patients may not require the

same level of dialysis adequacy to achieve adequate outcomes. This is particularly important because

low and low average transporters may be unable to exceed certain threshold creatinine clearance

levels with any currently reasonable dialysis prescription.

However, transport type did not influence outcome in the ADEMEX study [21]. Thus, individualizing

the patients' prescription as related to transport type may not affect survival, if the transport

characteristics are not related to comorbidities. However, the prescription should be adjusted

according to transport type to minimize glucose and fluid absorption and optimize fluid and solute

removal.

Peak BUN as determinant of well-being — A minimum weekly Kt/Vurea of 1.7 in CAPD is well

below the value achieved with hemodialysis. As an example, the minimum recommended Kt/Vurea for

each hemodialysis is 1.2 which, in a typical patient dialyzed three times per week, represents a

weekly Kt/Vurea of 3.6. (See "Kt/V and the adequacy of hemodialysis".)

However, CAPD patients do as well clinically as those undergoing hemodialysis despite the lower

Kt/Vurea. This was best shown in the equivalent mortality at two years in the HEMO and ADEMEX

trials despite markedly differences in attained Kt/V in the two trials. (See "Kt/V and the adequacy of

hemodialysis".)

One explanation for this seeming paradox is that the BUN may not be an optimal index of the

retention of uremic toxins and that the more effective clearance of larger "middle molecules" with

CAPD is responsible for the similar outcome [38]. (See "Uremic toxins".)

Perhaps more important is that the likelihood of developing early uremic symptoms, such as

decreased appetite, may be related to the peak plasma value of urea and other small uremic toxins

rather than the average value. The BUN rises between hemodialyses and then falls dramatically


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during dialysis; as a result, a higher net Kt/Vurea with hemodialysis is required to produce a peak

predialysis BUN that is equivalent to the steady state level seen with continuous peritoneal dialysis.

The similarity in peak values may explain the similarity in patient well-being despite the much lower

weekly Kt/Vurea with CAPD [15,38].

CALCULATION OF SOLUTE CLEARANCE

Weekly Kt/Vurea — The weekly Kt/Vurea in continuous PD patients can be estimated from the

following parameters: the daily peritoneal urea clearance (Kt) is the sum of the product of all drain

volumes (peritoneal and residual kidney) and the ratio of the urea concentration in the pooled

drained dialysate or urine to that in the plasma (D/P urea). The volume of distribution of urea (V) is

estimated to be equal to body water.

As an example, suppose a 70 kg man on CAPD has a drain volume of 10.5 L/day, and D/P urea of

0.95; thus, the Kt is equal to 10 L (10.5 x 0.95). The urea volume of distribution (V) is roughly equal

to 42 L (60 percent of lean body weight in men, 55 percent in women). As a result:

Daily Kt/Vurea = 10 ÷ 42 = 0.24

The weekly Kt/Vurea is equal to this value multiplied by 7:

Weekly Kt/Vurea = 0.24 x 7 = 1.68

This value probably reflects inadequate dialysis. This representative calculation illustrates that an

adequate solute clearance goal in terms of Kt/Vurea is often difficult if not impossible to attain with

the historical "standard" dialysis prescription of 2.0 L four times per day, particularly among larger

anuric patients with low and low average transport characteristics.

Patients with a low delivered Kt/Vurea who appear to have a dialysis prescription that would be

predicted to result in an adequate dose of dialysis should be evaluated for the source of the problem.

Possible causes include lack of adherence to the dialysis prescription, actual dwell times that are

different from those that are prescribed, a change in peritoneal transport type, loss of residual kidney

function, incomplete drain, and a hypercatabolic state. (See "Peritoneal equilibration test" and

"Problems with solute clearance and ultrafiltration in continuous peritoneal dialysis".)

Adjustment for body size — To standardize dosing targets, the patients Kt for urea has historically

been normalized by the patients volume of distribution for urea or V. The formula used to estimate V

becomes less accurate the more disparate the persons actual weight is (obese or malnourished

patients) from his or her ideal weight.

Marked differences in the calculation of Kt/Vurea can be seen depending upon the equation and the

weight (ideal or actual) used to estimate V [39,40]. As a result, very large patients may occasionally

appear underdialyzed (measured Kt/V is low) despite doing clinically well, because of problems

associated with assuming a fixed percentage of body weight for the volume of distribution (V) of urea.

These differences are also significant when assessing the volume of distribution in severely

malnourished individuals. In the setting of an unchanging Kt, the measured Kt/V in a patient losing

weight would actually appear to increase at a time that the prescription was not changing. If the

initial cause of the weight loss was suboptimal solute clearance, the measured Kt/V using the lower

actual weight would be misleading.

The original National Kidney Foundation Dialysis Outcome Quality Initiatives (NKF-DOQI) guidelines

recommended the use of the patient's actual weight; however, in malnourished patients, they

recommended adjusting their target weight by the ratio of ideal/actual weight (essentially the same

concept as using the ideal weight) to promote anabolism and enough solute clearance to equal the

metabolic needs of an increased protein intake. The original guidelines were unclear for patients


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significantly above their ideal weight (obese patients). We agree with the 2006 NKF-KDOQI guidelines

that recommend using ideal body weight in all cases [29].

Residual renal function — The value for total weekly Kt/Vurea may include the contribution of

residual kidney function which, for urea kinetics, can be estimated from a 24-hour urine collection for

urea clearance. In cases where the patient has significant residual renal function (arbitrarily defined

as a residual kidney volume of greater than 100 mL/day in the 2006 NKF-KDOQI guidelines [29]),

both the peritoneal and the residual renal components of solute clearance are used in the calculation

of total solute clearance.

Even relatively small residual urea clearances may contribute substantially to overall clearance

among patients undergoing PD. As an example, if the remaining urea clearance is 2 mL/min in a 70

kg patient, the total residual Kt/Vurea would be approximately 0.4 units per week (weekly urea

clearance of 17 L divided by total body water of 40 L). In such a patient, if the total weekly Kt/Vurea

was 1.7, then the residual clearance would constitute a substantial portion (about 24 percent) of the

weekly targeted Kt/Vurea (0.4/1.7). In these cases, failure to account for the loss of residual renal

function over time by increasing the peritoneal component to compensate for the loss, could lead to

signs of underdialysis even though there has been no decline in the peritoneal dialysis efficiency

(graph 4) [16,41,42].

A dialysis center may elect to ignore residual kidney function in calculating a person's total solute

clearance, delivering at least the minimal recommended total solute clearance by peritoneal dialysis

alone right from the initiation of dialysis. In this case, the residual kidney function would be of

additional benefit. However, if the patient had a significant amount of residual kidney function, this

approach may make the peritoneal prescription more demanding or time consuming than it would

clinically need to be.

Patients with a significant amount of residual renal solute clearance may initially be treated with

intermittent peritoneal dialysis (such as nightly cycler peritoneal dialysis with a dry day). This may

allow one to prescribe less demanding and intrusive regimens, while still providing adequate overall

clearances. Using kinetic modeling, one study found that a weekly Kt/Vurea of 2.0 could be

maintained for approximately 1.5 years by using only one or two nightly exchanges in the patient

with significant residual function [43]. This would be even easier to achieve with the new minimal

total solute clearance recommendations of a weekly total Kt/V of > 1.7. In this setting, when residual

kidney function is a significant portion of total solute clearance, the total solute clearance (peritoneal

and residual kidney function) needs to be closely monitored and the delivered dose kept above the

minimal at all times. The current K/DOQI guidelines recommend that residual renal clearance should

be monitored every other month.

Peritoneal creatinine clearance — Calculation of the peritoneal creatinine clearance (CCr) is

similar to that for the Kt/Vurea: mean daily drain volume times the D/P creatinine times seven days

per week. Again, the total creatinine clearance is due to both peritoneal and residual kidney

clearance. When calculating the contribution of residual kidney function, it is recommended that the

glomerular filtration rate be estimated from the sum of the urea and creatinine clearances divided by

two; this correction accounts for the overestimation of GFR induced by creatinine secretion. (See

"Calculation of the creatinine clearance".)

National guidelines from the United States, Canada, and Europe no longer recommend the use of

creatinine clearance as the surrogate solute for "dialysis adequacy." However, it is acknowledged that

one could continue to monitor 24 hour dialysate and urine creatinine removal because it is an

estimation of muscle mass and creatinine clearance mirrors phosphate clearance in PD. (See '2006

K/DOQI guidelines' above.)

Differences between small and middle molecular weight solute clearances — There are


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differences between the clearance of small and middle or large molecular weight solutes with

peritoneal dialysis and residual kidney function. As you increase the number of exchanges/day,

instilled volume/exchange or length of a dwell, one may increase small solute clearance but not

necessarily increase middle molecular weight clearances. The following is a brief review of this

subject.

The ability to attain higher CCr values with a change in the peritoneal prescription is particularly

affected by transporter status. Anuric low and low average transporters are much less likely to

achieve a weekly CCr value of 60 L/1.73m2 when adhering to any reasonably practical dialysis

prescription. Kinetic modeling, confirmed by clinical experience, predicts that the average anuric

patient with a peritoneal Kt/Vurea of 2.0 has a CCr of only 53 to 55 L/week [44-46]. This was one

reason for the lower minimal creatinine clearance target values in patients who have low or low

average peritoneal membrane transport characteristics in the 2000 revision of the Canadian and

NKF-KDOQI guidelines [47,48].

During a long dwell, diffusive transport tends to stop because equilibrium between dialysis and plasma

has been reached. The dwell time needed to reach equilibrium varies based on the patient's peritoneal

membrane transport characteristics and the molecular weight of the solute in question. For instance,

urea will reach equilibrium faster than creatinine which will equilibrate faster than beta 2

microglobulin. The daytime dwell for CCPD (14 to 15 hours) tends to be longer than the nighttime

dwell (9 to 10 hours) for CAPD. While the nighttime exchanges of CCPD are relatively shorter than

the daytime exchanges in CAPD. Therefore, with the same weekly Kt/V urea, low and low average

transporters may have lower creatinine clearances on cycler therapies than high and high average

transport patients.

FLUID BALANCE — An association between excessive body fluid and enhanced mortality may also

exist among patients undergoing peritoneal dialysis [9,10,49]. Although a low Kt/Vurea and

hypoalbuminemia appear to directly correlate with lower overall survival, these factors are not totally

independent of fluid volume:

The Kt/Vurea, by definition, correlates inversely with volume; a low Kt/Vurea may therefore

represent an excess of total body fluid as well as inadequate solute clearance [10].

Excess hydration can significantly lower serum albumin concentrations by dilution [25,50-52].

As a result, the correlation between poor survival and a low Kt/Vurea or serum albumin concentration

may actually be due in part to excess body fluid volume. In a prospective study from the Netherlands,

for example, a significant increase in the relative risk of death was associated with decreased

clearance among 130 anuric patients undergoing PD [25]. In addition, since inadequate ultrafiltration

is common in high transport patients, the relatively higher mortality historically observed among

these patients could be due to increased hydration [9,10,25].

However, these correlations are only indirect. Controlled studies of UF volume dialysis dose in rapid

transporters and low transporters are needed to properly assess the relative contribution of excess

intravascular volume versus transport status to survival. Observational data where patients tend to

use APD and some are also using alternative dialysis fluids, such as icodextrin, fail to report a

relationship between transport status and risk of death [35,38].

Greater fluid removal (peritoneal and kidney) has also been found to be a favorable predictor of

improved relative risk of death in observational studies [11]. However, the interpretation of this

finding remains unclear. The greater need for fluid removal may be a surrogate for well being and

increased intake, convective clearance of middle molecules, and/or increased blood pressure

[11,53,54].


9 of 20 15-07-2010 01:23

The 2005 European Best Practices Guidelines have published recommendations concerning

ultrafiltration goals. They suggested that, in anuric patients, the minimum target value is 1.0 L/day

[30].

The 2006 NKF-KDOQI guidelines have acknowledged the importance of blood pressure control and

maintenance of euvolemia in reducing the risk of death in peritoneal dialysis patients [29]. These

guidelines stress that one should achieve euvolemia and optimal blood pressure control, and address

possible ways to achieve these goals. However, they do not recommend a minimal daily ultrafiltration

volume amount.

Assessment — The accurate recognition of fluid overload in patients treated with chronic PD can be

difficult, particularly among those without obvious symptoms or signs of an excess of total body fluid

(eg, peripheral edema, elevated jugular venous pressure, and basilar rales). A more subtle degree of

fluid overload may be indicated by the presence of hypertension alone.

Among such patients, a successive increase in ultrafiltration to attain a normal blood pressure without

reliance upon medications is one method to attain adequate fluid balance [55]. Unfortunately, an

accurate noninvasive method to regularly assess total body water in the normotensive patient with

lesser degrees of fluid excess is not yet available [56].

Treatment — Patients with evidence of fluid overload should be evaluated and, if indicated, the

peritoneal dialysis prescription changed. Not all causes of volume overload are the result of peritoneal

membrane failure. More often it is due to changes in dietary habits, loss of residual renal function, or

mismatch of peritoneal prescription to the patients peritoneal membrane transport characteristics.

Interventions that one may consider to improve volume status include but are not limited to the

following: dietary sodium restriction; addition of loop diuretics if the patient has significant residual

kidney volume; change in peritoneal prescription with special attention to ultrafiltration profile of the

long dwell; and/or consideration of using alternative osmotic agents. Why this occurs and how it can

be treated are discussed separately. (See "Problems with solute clearance and ultrafiltration in

continuous peritoneal dialysis".)

PATIENT COMPLIANCE — The above recommendations assume that the patient is compliant with

the dialysis prescription. Unfortunately, this is often not the case. One report, for example, found that

26 percent of stable CAPD patients were not compliant with the recommended regimen [57]; this

figure was based upon the assumption that a value greater than one for the ratio of measured to

predicted creatinine generation was due to noncompliance. However, an elevation in this ratio is a

poor predictor of compliance with the PD prescription [58-61]. Despite the lack of easy documentation

of noncompliance in PD, this remains an important issue, since as many as 11 percent of patients who

switch to hemodialysis do so because of noncompliance.

An important influence upon compliance is the number of exchanges per day, with an increased

number having an adverse impact upon the quality of life. Compliance may therefore be problematic

among those in whom an increased number of exchanges is prescribed to obtain the recommended

dialysis dose. To minimize the burden early in the course of renal replacement therapy if one is

targeting total solute clearance (residual kidney and peritoneal) as described above, one may only

need nightly peritoneal exchanges to achieve the minimal total solute clearance goal. Over time, as

residual kidney function continues to decline, this can be replaced by more peritoneal clearance.

To encourage compliance, an alternative strategy is to utilize larger exchange volumes. Although

many patients are reluctant to use increased volumes because of the fear of abdominal discomfort,

this concern appears to be unfounded. This was illustrated in a blinded study in which 15 of 20

patients (75 percent) were unable to distinguish among 2, 2.5, and 3 liter exchange volumes [62]. In

addition, discomfort was not more common with the 3 liter exchange than with lesser exchange


10 of 20 15-07-2010 01:23

volumes, and increasing exchange volumes was significantly associated with increasing clearances of

both creatinine and urea.

INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients.

(See "Patient information: Peritoneal dialysis".) We encourage you to print or e-mail this topic review,

or to refer patients to our public web site, www.uptodate.com/patients, which includes this and other

topics.

SUMMARY AND RECOMMENDATIONS

Minimal total solute clearance target values — Based on the data previously presented and other

findings, minimal weekly total target clearance values in terms of Kt/V urea and creatinine clearance

have been published over the last several years by United States and international societies. There is

a general consensus that the previously recommended target weekly dialysis doses are not needed for

most patients, which may have unnecessarily resulted in patients transferred to hemodialysis because

of perceived inadequate dialysis with PD. (See 'Solute clearance' above.)

The ADEMEX study and Hong Kong trial results have shown that for a population as a whole, using

standard peritoneal dialysis regimens, attempts to maintain the previously recommended solute

clearance goals are not necessary. (See 'ADEMEX and Hong Kong trials' above.)

Therefore, the 2006 NKF-KDOQI guidelines revised the minimal delivered total solute clearance goals.

The 2006 K/DOQI work group recommend the following:

For patients with residual kidney function (RKF) (considered to be significant if urine volume is

>100 mL/day), the minimal "delivered" dose of small solute clearance should be a total (PD and RKF)

Kt/Vurea of at least 1.7/week.

For patients without RKF (considered insignificant if urine volume is <100 mL/day), the minimal

"delivered" dose of small solute clearance should be a peritoneal Kt/Vurea of at least 1.7/week

(See '2006 K/DOQI guidelines' above.)

Consistent with this view is the 2005 European Best Practices Guidelines that suggest a minimum

weekly target Kt/Vurea of 1.7.

We recommend that the minimal delivered total solute clearance of Kt/Vurea should be at least

1.7/week for patients undergoing continuous ambulatory peritoneal dialysis (Grade 1B). We also

recommend measures aimed at preserving residual renal function among peritoneal dialysis patients

(Grade 1B). Our specific recommendations with evidence grade for patients undergoing APD is found

below.

The minimal delivered total solute clearances recommended in the new guidelines are correct based

on current evidence. However, these are minimal recommended doses for a population and individual

patients may require more dialysis. Patients should therefore be closely monitored, with the

possibility of prescribing more dialysis if the clinical situation warrants a higher prescribed dose.

We also feel it is important to remind the reader of a few caveats. The prospective randomized trials

that were used to formulate the new guidelines were conducted in short term studies in Mexico and

Hong Kong. These populations are different from the typical patient in the United States. Protein

intake, size, effect of ethnicity on the therapy, compliance, and severity of comorbidities may vary

among these populations.

As a result, individuals may need relatively higher solute clearances than those recommended for the

peritoneal dialysis population as a whole. A requirement for higher values may be most applicable to

some patients in the United States, a country in which higher adequacy goals may be particularly


11 of 20 15-07-2010 01:23

necessary for a relatively older and sicker PD population. In addition, higher values may be necessary

in those eating relatively more protein who may have a metabolic need for relatively higher small

solute removal rates.

In our unit in the United States, we prescribe target doses that are sufficiently above the minimum

threshold levels to help ensure that the minimum level of dialysis dose has been delivered to all

patients. We aim for a target Kt/Vurea of 1.8/week.

Automated peritoneal dialysis — There are no prospective randomized trials that have looked at

relative risk of death in relationship to dose in automated peritoneal dialysis (APD) patients. We agree

with the 2006 K/DOQI work group who felt that the higher targets previously recommended are not

required with APD.

We suggest that the minimal dose of Kt/Vurea should be 1.7/week for those undergoing APD (Grade

2B). However, once the APD patient is anuric or with minimal urine volume, the patient should

undergo 24 hours/day of PD to optimize middle molecular weight solute clearance. This is because

randomized trials have only evaluated patients undergoing 24 hours/day of PD. (See 'Automated

peritoneal dialysis' above.)

Calculation of solute clearance — The weekly Kt/Vurea in continuous PD patients can be estimated

from the following parameters: the daily peritoneal urea clearance (Kt) is the sum of the product of

all drain volumes (peritoneal and residual kidney) and the ratio of the urea concentration in the

pooled drained dialysate or urine to that in the plasma (D/P urea). In cases where the patient has

significant residual renal function (arbitrarily defined as a residual kidney volume of greater than 100

mL/day), both the peritoneal and the residual renal components of solute clearance are used in the

calculation of total solute clearance. (See 'Calculation of solute clearance' above.)

Fluid balance — An association between excessive body fluid and enhanced mortality may exist

among patients undergoing peritoneal dialysis. Patients with evidence of fluid overload should be

evaluated and, if indicated, the peritoneal dialysis prescription changed.

Interventions to improve volume status may include: dietary sodium restriction; addition of loop

diuretics if the patient has significant residual kidney volume; and/or change in peritoneal

prescription with special attention to ultrafiltration profile of the long dwell or consideration of using

alternative osmotic agents. (See 'Fluid balance' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

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Dumler, F. Hypoalbuminemia is a marker of overhydration in chronic maintenance patients on

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52.

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GRAPHICS


16 of 20 15-07-2010 01:23

Albumin at onset of dialysis predicts mortality

Correlation of the risk of mortality according to the

plasma albumin concentration obtained within six weeks

of starting maintenance dialysis in 2897 patientsreceiving hemodialysis and 666 patients treated with

continuous ambulatory peritoneal dialysis.

Hypoalbuminemia was associated with increasedmortality, particularly at plasma concentrations below

3.0 g/dL (30 g/L).

Data from Held, PJ, Port, FK


17 of 20 15-07-2010 01:23

Kt/V predicts survival in continuous PD

Predicted probability of survival in patients treated with

continuous peritoneal dialysis according to the weekly Kt/V.A progressive decline in two-year survival is noted at lower

values for Kt/V. The values were 81 percent at a Kt/V of 2.3

versus only 66 percent at a Kt/V of 1.5.Data from CANADA-USA (CANUSA) Peritoneal Dialysis Study Group, J Am

Soc Nephrol 1996; 7:198.


18 of 20 15-07-2010 01:23

Creatinine clearance predicts survival in continuous PD

Predicted probability of survival in patients treated with continuous

peritoneal dialysis according to the weekly creatinine clearance (CCr).A progressive decline in two-year survival is noted at lower values for

CCr. The values were 86 percent at a CCr of 95 L/week versus only 72

percent at a CCr of 55 L/week.Data from CANADA-USA (CANUSA) Peritoneal Dialysis Study Group, J Am Soc Nephrol

1996; 7:198.


19 of 20 15-07-2010 01:23

Decline in solute clearance over time

Total solute clearance over time, as measured by weeklyKt/V (top panel) and creatinine clearance (CCr, lower

panel), in patients on continuous peritoneal dialysis.

Although peritoneal clearance (middle columns) remainsconstant, total clearance (left columns) falls because of a

progressive loss in residual renal function (RRF, right

columns).Data from Burkart, JM, Schreiber, M, Korbet, SM, et al, Perit Dial Int

1996; 16:457.

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