Nephrology Hypertension

Peritoneal Dialysis: Prescription and Assessment of Adequacy

How should patients with chronic kidney disease requiring peritoneal dialysis be managed?

How do you determine an appropriate peritoneal dialysis (PD) prescription (incident or prevalent patient)? - general issues

Initial factors to consider when planning for a PD prescription (incident or prevalent patient):

1. patient's lifestye (affects the PD exchange schedule, and possibly the mode of PD, ie. continuous ambulatory peritoneal dialysis [CAPD] vs. automated peritoneal dialysis [APD])

Examples:

-does the patient work full-time? APD might suit the patient best, allowing them to forego daytime exchanges and therefore carry on with the workday uninterrupted

-is the patient's spouse a light sleeper? perhaps the low sounds of a cycler might disrupt the spouse's sleep, and CAPD would be a better match

2. body size (affects the amount or dose of PD needed, i.e. how many liters of dialysate per inflow and how many exchanges per day)

3. amount of residual kidney function (affects the amount/dose of PD needed)

Examples:

-a patient with a residual kidney glomerular filtration rate {GFR) of 7 mL/min may initiate NIPD, with a "dry day", or may be adequately dialyzed with 2-3 exchanges per day as long as their kidney function remains stable

-an anuric patient should not have a "dry day," because middle molecule clearance is largely dwell time dependent (nighttime cycler exchanges provide only short dwell times)

Additionally, prevalent PD patients might have data regarding peritoneal membrane transport characteristics (PET data). Incident patients do not have PET data available at the time of PD initiation (remember that the intial PET should not be performed before 4 weeks of continuous PD), and one should assume average membrane transport characteristics in these patients.

How should the PD prescription be changed when adequacy targets are not met?

CAPD:

  • increase inflow volume per exchange (most effective, especially in low, low average, and high average transporters)

  • increase the number of day exchanges (typically less effective than increasing the inflow volume)

  • increase the ultrafiltration volume (ultrafiltration causes solvent drag, which leads to additional solute clearance) by either using hypertonic fluid or using icodextrin for the long overnight dwell (icodextrin should not be used for dwell times less than 8-9 hours)

  • consider changing to APD (particularly in high/rapid transporters)

APD:

  • increase the inflow volume per exchange (most effective)

  • increase the number of cycles (caution: too many cycles create ineffective dialysis, since more time is spent draining and filling dialysate than dwelling dialysate; additionally, frequent short cycles leads to sodium sieving which can create morning thirst due to hypernatremia)

  • add daytime manual exchanges ("high dose PD")

  • increase ultrafiltration (ultrafiltration causes solvent drag, which leads to additional solute clearance) by either using hypertonic fluid or using icodextrin for the long day dwell (icodextrin should not be used for dwell times less than 8-9 hours)

  • consider changing to CAPD (in low transporters)

What is a typical initial APD prescription?

APD refers to the PD procedure which utilizes an automated cycling machine to perform the PD dialysate exchanges.

APD is further classified as either:

1. NIPD, nightly intermittent PD; using the cycler at night followed by a "dry day" without dialysate in the peritoneum

2. CCPD, continuous cyclic PD: nightly PD using the cycler, followed by a day dwell; dialysate dwells throughout the day until the time of reconnection to the cycler at night

3. High-dose APD (a.k.a. PD plus): nightly PD with the cycler plus a daytime dwell with 1+ manual daytime exchanges before reconnecting to the cycler at night

3. Tidal PD: nightly APD, each cycle drains a percentage of the infused volume (incomplete draining) before refilling the peritoneum, therefore allowing a constant amount of dialysate to remain in the peritoneum.

The typical APD prescription should take into account the following factors:

1. absence or presence of daytime dwell

2. inflow volume

(1500 - 2000mL is the typical starting volume; larger patients or those needing additional solute clearance may require 2500 - 3000mL)

3. total cycler therapy time

dependent upon patient lifestyle characteristics and needs, and the amount of solute clearance needed. More time=more clearance

4. number of cycles per night, typically 3 -5 cycles/night.

more than 5 cycles per night should be avoided if possible because each additional cycle causes a greater proportion of the total cycler time to be spent draining and filling, rather than dwelling. Additionally, many overnight short dwells create a sodium sieving effect, thus leading to morning thirst and increased oral intake.

5. tonicity of dialysate

this is a dynamic factor, and changes will be made on a daily or weekly basis according to the patient's extracellular fluid status.

6. NIPD

This modality preferably should be used only in patients who have significant residual kidney function, because short PD exchanges provide poor middle molecule clearance. Residual kidney function, or a long dwell in the daytime, provides middle molecular solute clearance that NIPD cannot provide.

What is a typical initial CAPD prescription?

The most common initial CAPD prescription (Table I) is probably the 4x2L presciption, meaning 4 exchanges per day, with 2L inflow volume for each exchange. the most common variations on this standard prescription take into consideration patient size and residual kidney function (RKF).

Table I.

Typical CAPD prescription based upon body size
BMI inflow vol. exchanges/day comments
< 25 1,500 - 2000 mL 3 - 4 if needed, larger fill volumes should be used at night (supine)
25 - 30 2000 mL 4
>30 2500 - 3000 mL 4 - 5 larger fill volumes should be used at night (supine)
additional comments:(1) if significant residual kidney function is present,can consider NIPD (dry day) or fewer cycles/smaller inflow volumes(2) the prescribed dialysate tonicity will vary depending upon volume status and membrane transport status. See text for details

Considerations when writing the initial CAPD prescription:

  • Smaller patients can usually meet solute clearance targets with smaller inflow volumes of 1,500 - 2000 mL, whereas large patients typically require inflow volumes of 2,500 mL or more.

  • Inflow volumes which are too large for a particular patient can be associated with discomfort (abdominal distension, back pain, decreased appetite from bloated sensation); however, some patients may grow accustomed to the inflow volume with time.

  • Larger inflow volumes increase intraperitoneal pressure, and therefore increase the risk of developing a new hernia or peritoneal leak. To decrease the intraperitoneal pressure, larger inflow volumes should be preferentially used at night, while supine; if the patient has large inflow volumes during the day the patient should avoid any activity or position which could further increase intraperitoneal pressure (e.g.,g. Valsalva maneuver, squatting, chronic coughing, heavy lifting, etc.)

  • If signficant residual kidney function is present, fewer exchanges per day may be sufficient (as long as the total peritoneal + renal Kt/V meets targets); in these cases NIPD (nocturnal dialysis only) can also be considered. In these patients, residual kidney function must be measured frequently (i.e. every 2 months) to detect any decrement in RKF that would necessitate a change in the PD prescription in order to meet solute clearance targets.

  • The term "incremental PD" refers to the process of initiating peritoneal dialysis using fewer exchanges (and often at least one "dry" period during the day without a PD fluid dwell) when a patient has significant residual kidney function, and subsquently increasing the PD "dose" over time, as needed to meet solute clearance and ultrafiltration targets.

How is Kt/Vurea calculated in peritoneal dialysis?

In peritoneal dialysis: total Kt/Vurea = peritoneal Kt/Vurea + kidney Kt/Vurea

K = dialyzer clearance rate (L/day) - in PD the dialyzer is the peritoneal membrane

t = dialysis time

V = volume of distribution of urea (approximately the total body water volume, or TBW) (L)

peritoneal Kt/Vurea = [dialysate urea] / [BUN] * (total volume of drained effluent in 24 hours)

Vurea(use an estimate of TBW, or use Watson formula)

Show an example calculation of peritoneal Kt/Vurea in a PD patient

Example:

A 45 year old well-nourished male is on APD.

PD prescription: 4 nocturnal cycles with inflow volume of 2L each, last fill 2L Icodextrin.

His weight is 70kg.

24-hour collection of dialysate produces 12.5L of fluid with a dialysate urea concentration of 65 mg/dL. HIs BUN is 70 mg/dL.

His daily (24h) peritoneal Kt/V = [(65 mg/dL / 70 mg/dL) * 12.5L ] / (0.6 * 70) = 0.27

His weekly peritoneal Kt/V = 0.21 * 7days = 1.93

What is the definition of "adequate" peritoneal dialysis?

Adequate dialysis should be assessed clinically and not only by measurement of solute clearance. A sufficient dose of peritoneal dialysis is that which is associated with:

  • overall sense of well-being

  • absence of malnutrition

  • no uremic symptoms

  • biochemical balance

  • euvolemia

  • erythropoeitin-stimulating agent (ESA) responsiveness

In clinical practice, the concept of dialysis adequacy has become synonymous with the achieved solute clearance, particularly urea clearance which is most commonly measured as Kt/Vurea.

What is the target Kt/Vurea for peritoneal dialysis?

  • Current International Society of Peritoneal Dialysis (ISPD) guidelines recommend a minimum total (renal + peritoneal) Kt/Vurea of 1.7

  • Initial Kt/Vurea should be measured within 1 month of initiating peritoneal dialysis, and thereafter at intervals of no less than every 4 months.

  • Patients who rely on residual kidney function to meet the minimum solute clearance target (Kt/Vurea of 1.7) should have residual kidney function measurements every 1-2 months if feasible, but no less than every 4 months.

What is the target creatinine clearance in peritoneal dialysis?

The current iteration of the ISPD practice guidelines recommend a minimum target total Kt/Vurea of 1.7, but do not recommend a separate target for creatinine clearance in CAPD.

For patients using APD, a target creatinine clearance of 45 L/week/1.73m2 is recommended (in addition to a minimum total Kt/Vurea of 1.7), due to a more variable relationship between urea clerance and creatinine clearance in APD, as compared to CAPD.

Why is there a target creatinine clearance in APD and not in CAPD (per ISPD clinical practice guidelines)?

Creatinine is a larger molecule than urea and therefore is less rapidly equilibrated between the blood and dialysate than urea. Relatively short dwells typical with APD allow more urea than creatinine to be equilibrated per unit time. The longer dwells typically used in CAPD allow creatinine to more fully equilibrate between blood and dialysate during a dwell period than the shorter APD dwells; therefore longer CAPD dwells are less likely to show large differences between urea clearance and creatinine clearance than the APD dwells.

Why do solute clearance targets differ between peritoneal dialysis and hemodialysis?

There are several differences one must consider when comparing urea clearance (Kt/Vurea) targets for peritoneal dialysis (PD) hemodialysis (HD):

  1. Chronic hemodialysis is an intermittent therapy whereas peritoneal dialysis is a continuous therapy. Since PD is a slow and continuous dialysis therapy, urea is more equally equilibrated between the blood compartment and the extravascular body compartments in PD patients than in HD patients. The blood urea measurements used to calculate Kt/Vurea are taken from an equilibrated urea pool in PD, whereas in HD urea is measured from a single pool of urea (blood compartment).

  2. Peritoneal dialysis urea solute clearance is reportedly as weekly Kt/Vurea whereas in HD it is typically reported as a per session Kt/Vurea

  3. HD is an intermittent therapy, and thus causes peaks and lows in the blood urea concentration (BUN) during the week. Thus, one cannot simply compare the minimum weekly PD Kt/Vurea target of 1.7 to a "weekly" HD Kt/Vurea target of 3.6 (Kt/Vurea of 1.2 per session x 3 days per week = 3.6); rather, standardized Kt/Vurea must be used when comparing HD (any schedule of HD) to PD.

Despite these differences, PD and HD generally offer similar outcomes. Why is this so?

1. Standardized Kt/V: when standardized, the weekly Kt/Vurea provided by 3 weekly HD sessions (each with a Kt/Vurea of 1.2) is equivalent to a weekly PD Kt/Vurea of approximately 2.0. (equivalent degree of urea removal).

2. Peak and valley hypothesis: intermittent HD produces peaks and valleys of solute concentrations due to its intermittent nature whereas PD is a continuous therapy. Peak concentrations of urea (and other solutes) may be more harmful to the patient than steady levles, so a higher Kt/Vurea is required with HD than PD.

What is the difference between CAPD and APD?

The peritoneal dialysis procedure is typically referred to as either continuous ambulatory peritoneal dialysis, also known as "manual" PD, or automated peritoneal dialysis, otherwise known as "cycler" PD.

APD is classified further into the following categories:

1. NIPD, nightly intermittent PD; using the cycler at night followed by a "dry day" without dialysate in the peritoneum

2. CCPD, continuous cyclic PD: nightly PD using the cycler, followed by a day dwell; dialysate dwells throughout the day until the time of reconnection to the cycler at night

3. High-dose APD (a.k.a. PD plus): nightly PD with the cycler plus a daytime dwell with 1+ manual daytime exchanges before reconnecting to the cycler at night

3. Tidal PD: nightly APD, each cycle drains a percentage of the infused volume (incomplete draining) before refilling the peritoneum, therefore allowing a constant amount of dialysate to remain in the peritoneum. At the end of the nocturnal cycle, the peritoneum is typically fully drained until empty

The main factors affecting patients' choice when deciding between CAPD and APD are: (1) patient preference, (2) availability of the technique at the home dialysis unit, and (3) cost (APD can be more expensive in some areas).

A patient's peritoneal membrane transport characteristics may also play a role in deciding between CAPD and APD. Slow transporters take more time to equilibrate solutes between the blood and dialysate, and might benefit from the longer dwell times associated with CAPD, whereas rapid transporters might benefit more from the shorter dwells associated with APD. Transport status (based on a patient's PET data), however, does not necessarily dictate the type of peritoneal dialysis a patient must use, especially in patients who do no have very rapid membrane transport (high transporter), since these patients can often achieve solute and ultrafiltration targets with either CAPD or APD.

Considerations for both types of PD are listed below.

CAPD:

does not require any machinery

uses 2L dialysate bags which are easy to lift and manipulate

no alarms or machinery noises to interrupt sleep

must have time during the day to perform several exchanges, each 30-40 minutes in duration

more connections = more potential contamination events

APD:

daytime is relatively free of dialysis-related activity

typically uses at least one large dialysate bags (5L or 6L)

potential sleep interruption from cycler alarms

can be done with less burden on a caregiver (caregiver sets up machine at night, disconnects in morning, no daytime exchanges)

Is there a survival advantage of CAPD over APD or vice versa?

The outcomes of CAPD and APD were found to be no different in a large study using the USRDS database. No signficant differences in adjusted survival rate between CAPD and APD. Additionally, there were no significant differences between the two modalities in either time depedent or overall relative risk for technique failure.

What are some of the signs and symptoms of inadequate peritoneal dialysis?

  • chronic nausea and/or vomiting

  • fatigue

  • sleep disturbances

  • pruritus

  • restless leg syndrome

  • anemia

  • hyperkalemia

  • hyperphosphatemia

  • worsened hyperparathyroidism

  • pericarditis

  • neuropathy

  • unexplained weight loss

  • worsened metabolic acidosis

  • volume overload

Are there clinical practice guidelines to inform decision making?

Which key studies have contributed to the evolution of the current guidelines for adequacy in peritoneal dialysis?

1981: National Cooperative Dialysis Study , and further analysis in 1985

This study was the first randomized control trial (RCT) to examine the effect of dialysis dose on outcome in hemodialysis. Patients were randomized to two different time averaged urea concentrations (TACurea of 50 mg/dL vs. 100 mg/dL) and two different treatment times. TACurea was found to inversely correlate with the likelihood of poor outcomes. Gotch and Sargent reanalyzed the data and introduced spKt/V as a measure of dialysis adequacy (PMID 3934452). In this report, hemodialysis outcomes were found to be superior when single pool (sp) Kt/V was 1.0 or higher, and from this a goal spKt/V of 1.2 developed as a clinical target (the additional 0.2 provided a buffer so that spKt/V remained > 1.0 at all times).

At this time there were still no signficant studies examining the effect of dialysis dose on outcomes in PD but the generalization that more dialysis provides better outcomes (as per the NCDS study) was extrapolated to the practice of PD

1996: CANUSA

This was the first study examining the effect of dialysis dose on technique success in PD. In this collaborative effort between researchers in Canada and the U.S.A, a prospective observational cohort of 680 patients were studied; 98% were on CAPD. In this study, renal and peritoneal clearances were assumed to be equivalent and were added together. The relative risk of mortality decreased by 6% for each 0.1 u/week increase in weekly Kt/Vurea, and decreased by 7% for each 5L/week/1.73m2 increase in creatinine clearance.

It was assumed in this study that: (a) Kt/Vurea remained constant over time, and (b) renal Kt/Vurea = peritoneal Kt/Vurea are equivalent, such that any loss in renal Kt/Vurea was made up for by an equal increase in peritoneal Kt/Vurea

2001: CANUSA reanalysis

This was a reanalysis of the original CANUSA data wherein renal and peritoneal Kt/Vurea were separated before data reanalysis. Important findings included: (1) PD outcome was predicted by renal Kt/Vurea but not peritoneal Kt/Vurea, (2) changes in survival over time were due to changes in residual renal function, (3) each 5L/week renal GFR was associated with a 12% survival benefit

2002: ADEMEX

Randomized trial of 965 CAPD patients in Mexico; patients were randomized to receive either a conventional PD prescription of 4 daily exchanges with 2L inflow, or additional PD to achieve peritoneal creatinine clearance (pCcr) of > 60L/week/1.73m2. Both groups had similar baseline residual kidney function, and outcome was measured based only upon peritoneal clearance differences.

The study achieved a good separation between the two groups (pCcr of 46 vs. 57 L/week/1.73m2). There was no difference in survival at the end of 2 years. Interestingly, the overall mortality rates in this study were similar to the 2 year survival rates seen in the HEMO trial, which evaluated the effect of dialysis dose on outcomes in hemodialysis

2003: Hong Kong Trial

320 incident PD patients were randomized to three target pKt/Vurea goals (1.5 - 1.7, 1.7 - 2.0, and > 2.0). This study achieved good separation between the groups, and residual renal function was the same in all groups. There was no difference in survival between the groups; however, the lowest Kt/V group (pKt/Vurea 1.5 - 1.7) exhibited more dropout due to inadequate dialysis, and also require higher doses of ESA to achieve hemoglobin targets.

What is the evidence?

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