Peritoneal Dialysis Prescription and Adequacy in Clinical Practice: Core Curriculum 2023

As the global prevalence of peritoneal dialysis (PD) continues to grow, practitioners must be equipped with prescribing strategies that focus on the needs and preferences of patients. PD is an effective form of kidney replacement therapy that offers numerous benefits to patients, including more flexibility in schedules compared with in-center hemodialysis (HD). Additional benefits of PD include salt and water removal without significant changes in patient hemodynamics. This continuous yet gentle removal of solutes and fluid is associated with better-preserved residual kidney function. Unfortunately, sometimes these advantages are overlooked at the expense of an emphasis on achieving small solute clearance targets. A more patient-centered approach emphasizes the importance of individualized treatment, particularly when considering incremental PD and other prescriptions that align with lifestyle preferences. In shifting the focus from small solute clearance targets to patient needs and clinical goals, PD remains an attractive, patient-centered form of kidney replacement therapy.

Introduction

Peritoneal dialysis (PD) is a type of kidney replacement therapy that is relatively simple and allows patients to receive treatment in the comfort of their home. Patients receiving PD also benefit from salt and water removal without the significant changes in blood pressure that may occur with hemodialysis (HD). Importantly, this continuous yet gentle solute and fluid removal may preserve remaining nephrons and in turn maintain the residual kidney function (RKF).

PD is less expensive than in-center HD in many jurisdictions and, given the rapidly rising cost of health care delivery, presents a viable alternative to HD. The lower cost associated with PD has led to an increase uptake in countries with a significant burden of poverty. Worldwide, approximately 11% of patients on dialysis receive treatment with PD. This prevalence is expected to increase in the coming years, given PD’s benefits coupled with the emerging evidence of utility in managing heart failure patients with diuretic-refractory volume overload. In treating patients with PD, prescriptions have also evolved to adopt a more patient-centered approach using incremental PD. Incremental PD provides incident patients with sufficient dialysis to facilitate adequate solute clearance while reducing the burden of intrusiveness compared with “full-dose” PD. This approach allows patients to gradually become accustomed to PD and may be associated with better quality of life and reduced cost.

As a result, practitioners must be familiar with various prescriptive strategies in caring for patients on PD. In this installment of AJKD’s Core Curriculum in Nephrology, we will review the principles of incremental PD and other aspects of individualized prescriptions that align with the patients’ day-to-day needs, moving away from solute kinetics and peritoneal membrane transport characteristics. We will also review the important concept of adequacy along with the pitfalls of Kt/V_urea measurements in PD.

How Do You Select an Initial PD Modality and Prescription?

Case 1: A 23-year-old woman with kidney failure secondary to lupus nephritis undergoes a laparoscopic PD catheter insertion. She comes to the dialysis unit 4 weeks later to begin training for PD at home. As part of the initial assessment, she completes a 24-hour urine collection and produces 1,860 mL of urine. She is completing her final year of undergraduate studies and wants to return to daily classes. She is curious about her initial PD prescription.

Question 1: What initial PD prescription would you recommend?

1. (a) Automated peritoneal dialysis (APD) at night without a daytime dwell.
2. (b) Two manual exchanges during the day only.
3. (c) APD at night with a daytime dwell.
4. (d) Continuous ambulatory PD (CAPD; including an overnight dwell).

Case 2: A 73-year-old man with kidney failure secondary to diabetic nephropathy completed a peritoneal equilibration test (PET) 2 months after starting PD. The results show a ratio of dialysate to plasma concentrations of creatinine (D/P_cr) of 0.32, suggesting low, or slow, membrane transporter status. He has read information online suggesting that he may need to do manual daytime exchanges because of his “low transporter status.” He currently manages 3 small businesses that require frequent travel between sites, and he is nervous about the prospect of doing manual exchanges during his busy daily schedule.

Question 2: Given his transporter status, what is the most appropriate prescription for this patient?

1. Change to CAPD.
2. Continue nightly cycler-based therapy.

Case 3: A 55-year-old woman with kidney failure secondary to IgA nephropathy has been on dialysis for 6 months with APD. She receives 3 exchanges per night in 7 hours on the cycler with a fill volume of 1,500 mL for each exchange. Her morning routine includes short jogs around her neighborhood, and as such she has been resistant to adding fluid in the abdomen during the daytime. Recently, she described some nausea and itchiness. Her laboratory investigations suggest underdialysis, with concentrations for bicarbonate of 18 mEq/L; phosphate, 9.2 mg/dL; and urea, 86.8 mg/dL (31 mmol/L). She has not missed any treatments, and her weekly creatinine clearance (CL_cr) on PD is 31 L/1.73 m².

Question 3: What adjustment would you make to the PD prescription?

1. (a) Add a daytime dwell with 1,500 mL of icodextrin
2. (b) Increase the number of exchanges to 4 and lengthen the treatment to 8 hours.
3. (c) Use 4.25% solutions with each exchange.
4. (d) Increase the fill volume from 1,500 mL to 2,000 mL.

For the answers to these questions, see the following text.

The Basics of Peritoneal Dialysis

The basic principle of PD involves instilling the peritoneal cavity with sterile solutions of different osmolality through a permanent indwelling silicone-based catheter in a process called an exchange. The exchange itself consists of 3 distinct phases: filling, dwelling, and draining. This allows for the solution within the peritoneal cavity to generate a chemical and osmotic gradient across the peritoneal membrane, facilitating the removal of toxins and water with PD fluid drainage. The overwhelming majority of solutions used in PD are glucose based, with higher concentrations exerting a greater osmotic gradient that leads to larger ultrafiltration (UF) volumes. PD solutions can be lactate or lactate/bicarbonate buffered, with the latter having a more neutral pH of 7.4 (Table 1). Clinical data have suggested that lactate/bicarbonate-buffered solutions reduce the generation of glucose degradation products (GDP) during the sterilization and storage of the dialysis fluid, and in this way they may confer clinical benefit. Although studies have previously demonstrated conflicting results about the clinical benefits of pH neutral/low-GDP solutions, a recent meta-analysis showed that these solutions are associated with better preservation of RKF. Despite these emerging data on RKF benefits, neutral pH solutions are primarily used in clinical practice as an alternative to lactate-buffered solutions in patients who experience infusion pain.

Table 1. Various Components in Peritoneal Dialysis Solutions for Lactate- and Bicarbonate- Buffered Solutions Highlighting the Different Osmolarity Depending on Dextrose Concentrations

Component	Lactate-Buffered Solution			Bicarbonate-Buffered Solution
	2.5%	4.25%	7.5%	2.5%
Sodium, mmol/L	132	132	132	132
Calcium, mmol/L	1.25/1.75	1.25/1.75	1.25/1.75	1.25
Magnesium, mmol/L	0.25	0.25	0.25	0.25
Chloride, mmol/L	96	96	96	96
Lactate, mmol/L	40	40	40	15
Bicarbonate, mmol/L	—	—	—	25
Dextrose, g/dL	2.5	4.25	—	2.5
Icodextrin, g/dL	—	—	7.5	—
Osmolarity, mOsm/L	396	484	282	396
pH	5.2	5.2	5.2	7.4

Higher dextrose concentration solutions have a higher osmolarity and exert greater osmotic pressures across the peritoneal membrane, resulting in greater ultrafiltration volumes.

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Transport across the peritoneal membrane occurs through pores of 3 different sizes: ultrasmall or aquaporin 1 (AQP1) pores, small pores, and large pores. The principle of transport across the pore sizes is described as the 3-pore model. AQP1 allows for the exclusive transport of water across the peritoneal membrane. Small pores allow the transport of both water and small solutes, including most electrolytes. And large pores allow for the movement of macromolecules such as immunoglobulins and other proteins.

 

The exchange of solutes and water occurs at the areas of the peritoneal membrane that are surrounded by capillaries and in contact with dialysate. This is called the “effective peritoneal surface area” and can vary with changes in vascular resistance or increases in the dialysate fill volume. For example, PD peritonitis leads to inflammation and consequent vasodilation of the capillary bed, which in turn increases the effective peritoneal surface area (more open capillary beds able to take part in transperitoneal flux). Peritoneal solute transfer rate can therefore increase in patients with PD peritonitis, leading to faster absorption of dextrose (glucose), early dissipation of the osmotic gradient, and transient loss of UF capacity.

Should Transporter Status Determine PD Prescriptions?

Using the PET, peritoneal membrane transport can be evaluated by assessing the transport of small solutes along with UF properties. For a given solute, equilibration ratios between the dialysate and plasma (D/P) are used to measure the diffusion that allows for quantification of small solute transfer rate across the peritoneal membrane, also referred to as the peritoneal solute transfer rate. The PET procedure involves filling the intraperitoneal cavity with 2,000 mL of a 2.5% or 4.25% dextrose solution. Once the abdomen is filled, up to 3 dialysate samples can be taken at separate time intervals. The mandatory dialysate samples should include the 4-hour sample and a sample from the stock solution used for the procedure. Dialysate samples drawn immediately after the fill and at the 2-hour interval are optional. In instances where sodium sieving is being assessed using a hypertonic dextrose-based solution, an additional dialysate sample should be drawn at the 1-hour interval. The sodium concentration in the dialysate sample after a 1-hour dwell allows for an indirect calculation of the free water transport across the peritoneal membrane. Blood samples need not be measured frequently, and a unique sample can be drawn at the 2-hour interval for plasma concentrations of sodium, urea, creatinine, and glucose to determine the D/P.

The ratio of the glucose concentration in dialysate at different time intervals after fill relative to the initial dialysate concentration is written as D/D_0(glucose). Historically, patients are then classified into 4 distinct categories (slow, slow average, fast average, and fast) based on the D/P_cr, D/P_urea, and D/P_Na (Fig 1). Patients classified as “fast transporters” have a rapid dissipation of the osmotic gradient in the dialysis fluid because the dextrose diffuses across the peritoneal membrane more quickly. This rapid dissipation leads to less UF and even reabsorption of fluid toward the end of a longer dwell. As result, cycler-based therapies had been historically favored in “fast transporters” due to the shorter dwells with each exchange, thus reducing the risk of fluid reabsorption.

By contrast, “slow transporters” have slower loss of dextrose from the PD fluid and maintain their osmotic gradient for longer periods of time. It followed from this observation that slow transporters would be better suited for longer dwells with manual exchanges. In theory, the longer dwells were aimed at maximizing diffusive transport with the maintenance of the osmotic gradient. Despite the aims of this theoretical approach to capitalize on peritoneal membrane transport properties, it is not ideal in routine clinical practice.

Categorizing patients based on peritoneal solute transfer rate has limitations in clinical practice because these values function more like continuous variables than clearly distinct groups. In addition, a strong center effect has been observed. Therefore, practitioners should consider a more practical approach to PD prescriptions that prioritizes the patient’s preferences and positive clinical outcomes over peritoneal membrane transport characteristics.

Prescribing Peritoneal Dialysis

PD exchanges can be provided to patients through manual exchanges or through APD using pneumatic/hydraulic cyclers. Automated cyclers are used while patients sleep, allowing for small solute exchange and effective UF with frequent exchanges. Beyond its efficiency in achieving effective solute clearance and fluid removal, cycler-based therapy is a favorable option among patients with busy daytime schedules. Modern day cyclers have evolved, and they offer greater precision and remote monitoring that allow for tailoring of the prescription based on patient needs.

Despite the benefits of cyclers, their utilization depends on availability, training capacity, and local resources. For example, in countries where government reimbursement policies are limited, overall PD prevalence and cycler use tends to be relatively low. Manual exchanges (ie, CAPD) are more cost-effective and have higher utilization in low-resource settings. With CAPD, patients typically undergo 3-4 exchanges per day depending on clinical status and patient preferences. CAPD is an excellent option for patients who do not wish to be connected to a cycler during sleep and have more flexibility in daytime schedules to perform exchanges. It also affords greater portability for patients who travel frequently without having to transport their cyclers. Although the terms “exchanges” and “cycles” may be used interchangeably, practitioners should be aware that “cycles” usually refers to APD therapy and “exchanges” usually refers to CAPD.

 

Once a modality has been chosen, the prescription of the fill volume and number of exchanges must be finalized. Most patients can tolerate a maximum fill volume of 1,250-1,500 L/m² or about 2,000-2,500 mL per exchange. In the average adult patient, this will result in intraperitoneal hydrostatic pressures of less than 18 cm of H₂O. Although there are variations in intraperitoneal pressure (IPP) depending on patient positioning, an IPP of greater than 18 cm of H₂O is usually associated with discomfort. When patients are supine, the IPP is lowest; as a result, larger fill volumes are more tolerable at night compared with during the day when IPP is increased with either standing or sitting. Despite the opportunities for slightly higher volumes during sleep, fill volumes beyond 2,000-2,500 mL are not usually recommended given the increased risk of patient discomfort.

 

The principles of incremental PD can be used when starting patients on dialysis, allowing practitioners to tailor the PD prescription with a focus on laboratory investigations, clinical symptoms, and patient preferences. Incremental PD allows for patients who are new to the therapy to become comfortable with the treatment rather than beginning with a more demanding regimen. Initial large doses of PD can sometimes be an emotionally overwhelming experience for those who are new to treatment and carry significant burden of intrusiveness for many individuals in maintaining their regular routines.

There are also some important drawbacks that practitioners must consider with incremental PD. These drawbacks include more frequent monitoring of RKF, risk of underdialysis, and decreased patient acceptance to increasing the dose of dialysis if warranted (Fig 2).

 

Irrespective of a patient’s modality preference, the principles of incremental PD can be used for both CAPD and APD (Fig 3). For instance, patients who have expressed a preference for maintaining flexibility in their daytime schedule can be placed initially on 2-3 cycles for 6-7 hours per night on the cycler using fill volumes of 1,200-1,500 mL with each exchange. The prescription can be “incrementally” adjusted based on laboratory investigations and clinical assessments. In cases where a patient requires more solute clearance, there can be an incremental increase in the volume by 20%-30% up to a maximum of 2,000-2,500 mL. Alternatively, the time on the cycler can be increased along with the number of exchanges.

 

Patients should not be routinely prescribed >8 hours on cycler therapy because most people do not sleep or remain in bed for that amount of time. Additionally, prolonged treatments on the cycler may be an added burden for patients because it may restrict activity and impair overall quality of life. Patients should not receive more than 5 exchanges per night on the cycler because this leads to wasted time and inefficient dialysis.

As highlighted earlier, every exchange has 3 distinct phases: filling, dwelling, and draining. It is during the dwelling phase that effective peritoneal surface area is maximized with dialysate fluid. The filling and draining phases account for a combined 20-30 minutes, and during this time there is very little to no effective dialysis. For example, if 6 cycles are prescribed for a patient in 8 hours, that effectively equates to 120-180 minutes of inflow and outflow time, or nearly 3 out of 8 hours where little effective dialysis occurs. Consequently, this regimen leads to significant wasted time and inefficient dialysis (Fig 4). Furthermore, rapid exchanges can also cause suboptimal clearance of sodium given that the electrolyte-free water movement across AQP1 tends to occur in the first hours of each dialysate dwell. As a result, if exchanges are rapid and short, sodium cannot diffuse down its concentration gradient from blood to dialysate across the small pores. This “sodium sieving” leads to more water than sodium removal, causing a transient increase in plasma sodium levels. This hypernatremia can increase thirst in patients, leading them to drink excessively which may exacerbate volume overload.

Review of Cases 1 to 3

In the first case, the patient is relatively new to PD and has expressed an interest in continuing to attend university classes during the daytime. Although she does not yet have formal clearance studies available, her 24-hour urine output demonstrates good RKF, so she does not require a large initial PD prescription. As a result, APD at night with a daytime dwell (option (c) for question 1), also called continuous cyclic peritoneal dialysis (CCPD) is not the best option for this patient. Additionally, options (b) and (d) are not reasonable options because they require manual exchanges during the daytime. Therefore, the best answer to question 1 is (a): APD during the night can allow her flexibility in maintaining her busy schedule during the day as she can get her dialysis treatment while she sleeps.

 

Similarly, in the second case the patient has a very busy schedule with frequent travel between different sites. Manual exchanges would present significant challenges to his daily routine, which would not be a patient-centered approach for this individual. The patient would have greater daytime flexibility in his schedule if he received PD treatments during the night. Therefore, the best answer to question 2 is (b), maintain current nightly cycler-based therapy. Although his membrane transport characteristics suggest that he is a slow-average transporter, priority should be given to providing a prescription that is least disruptive to his lifestyle.

 

In the third case, the patient has been on PD for several months and is demonstrating clinical and biochemical signs of underdialysis probably because of declining RKF. In using an incremental PD approach, her fill volumes could be increased as an option but by 20%-30% as suggested with option (d) for question 3. In option (b), a fourth exchange is added, and the therapy time is extended by an additional hour for a total of 8 hours. In this case, options (b) and (d) are both reasonable to present to the patient. This allows the patient to be part of the decision-making process in choosing a suitable prescription that aligns with her personal preference. In most instances, patients are more likely to increase the fill volume rather than add an additional exchange or time on the cycler. The patient has expressed a preference to not have a daytime dwell at this time, thus option (a) would be inappropriate. In keeping with the principle of incremental dialysis, if and when her RKF declines in the future, a daytime “last fill” can be added. Finally, the use of hypertonic solutions with each exchange would be inappropriate because the patient does not have any signs to suggest volume overload. While the consequent increase in UF will increase solute removal, it exposes the patient to unnecessarily high concentrations of dextrose, increasing the risk of hyperglycemia and other downstream effects of glucose loading. Therefore, option (c) is equally inappropriate in this case.

 

How Is Adequacy Measured on PD?

Case 4: A 53-year-old woman has been on PD for 5 months and undergoes repeat adequacy testing. A few months earlier, her Kt/V_urea was 1.3, and her PD prescription was intensified to include a daytime dwell with icodextrin (1,000 mL) in addition to 5 exchanges on cycler overnight with each fill volume of 2,000 mL. Her repeat Kt/V_urea is 1.4, and she reports feeling well with no concerns. Her body mass index (BMI) is 39 kg/m², and all her relevant laboratory values are within the desired target range.