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.
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/Vurea 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?
- (a) Automated peritoneal dialysis (APD) at night without a daytime dwell.
- (b) Two manual exchanges during the day only.
- (c) APD at night with a daytime dwell.
- (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/Pcr) 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?
- Change to CAPD.
- 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 (CLcr) on PD is 31 L/1.73 m2.
Question 3: What adjustment would you make to the PD prescription?
- (a) Add a daytime dwell with 1,500 mL of icodextrin
- (b) Increase the number of exchanges to 4 and lengthen the treatment to 8 hours.
- (c) Use 4.25% solutions with each exchange.
- (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.
|Component||Lactate-Buffered Solution||Bicarbonate-Buffered Solution|
Should Transporter Status Determine PD Prescriptions?
The ratio of the glucose concentration in dialysate at different time intervals after fill relative to the initial dialysate concentration is written as D/D0(glucose). Historically, patients are then classified into 4 distinct categories (slow, slow average, fast average, and fast) based on the D/Pcr, D/Purea, and D/PNa (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.
Prescribing Peritoneal Dialysis
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.
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
Question 4: What are your next steps in the management of this patient?
- No changes are required to her prescription.
- She should be transitioned to HD.
- Increase the time on the cycler to 9 hours.
- Repeat the Kt/Vurea.
Measures of Adequacy: Kt/Vurea
Measures of Adequacy: Creatinine Clearance
Review of Case 4
- ➢Bargman JM. Myths in dialysis: we use Kt/V urea as a measure of adequacy of peritoneal dialysis. Semin Dial. 2016;29(4):258-259. https://doi.org/10.1111/sdi.12504
- ➢Bargman JM, Thorpe KE, Churchill DN. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol. 2001;12(10):2158-2162. https://doi.org/10.1681/ASN.V12102158 ★Essential Reading
- ➢Paniagua R, Amato D, Vonesh E, et al. Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol. 2002;13(5):1307-1320. https://doi.org/10.1681/ASN.V1351307 ★Essential Reading
- ➢Peritoneal Dialysis Adequacy Work Group. Clinical practice guidelines for peritoneal dialysis adequacy. Am J Kidney Dis. 2006;48(suppl 1):S98-S129. https://doi.org/10.1053/j.ajkd.2006.04.006
How Should Low Ultrafiltration Capacity and Solute Clearance Be Addressed?
Question 5: What would be your next steps in management?
- (a)Increase the dose of furosemide and metolazone.
- (b)Transition to HD.
- (c)Rule out catheter outflow obstruction.
- (d)Conduct a trial of 4.25% dextrose solutions.
Question 6: What would you offer the patient at this time?
- (a)Increase the time on the cycler to 11 hours.
- (b)Increase the volume with each exchange to 2,400 mL.
- (c)Transition to HD.
- (d)Repeat bloodwork and follow up in 2 months.
Management of Volume Overload in PD
Volume overload is a common finding in patients on PD and is primarily driven by imbalances between dietary salt and water intake and its removal. The common causes for volume overload in this population can be grouped into 3 categories: excessive fluid and/or salt intake, reduced RKF, and low peritoneal UF (Box 1). Observational data from Europe using bioimpedance analyses demonstrated that about 25% of patients on PD over a 2-year period had severe volume overload. Additionally, volume overload is associated with an increased risk of technique failure and death among patients receiving PD.
Common Causes of Volume Overload in PD
- •Excessive fluid and/or salt intake
- •Low residual kidney function
Low peritoneal ultrafiltration
- ⋄Mechanical problems (eg, catheter flow dysfunction, catheter malposition, and hernias)
- ⋄Peritoneal membrane dysfunction/rapid peritoneal solute transport rates in which osmotic gradient dissipates rapidly (from either inherited or acquired injury)
- •Suboptimal PD prescription
When Should a Patient Transition to Hemodialysis?
Review of Cases 5 and 6
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- ➢Elbokl MA, Kennedy C, Bargman JM, McGrath-Chong M, Chan CT. Home-to-home dialysis transition: a 24-year single-centre experience. Perit Dial Int. 2022;42(3):324-327. https://doi.org/10.1177/08968608211029213
- ➢Goossen K, Becker M, Marshall MR, et al. Icodextrin versus glucose solutions for the once-daily long dwell in peritoneal dialysis: an enriched systematic review and meta-analysis of randomized controlled trials. Am J Kidney Dis. 2020;75(6):830-846. https://doi.org/10.1053/j.ajkd.2019.10.004
- ➢Johnson DW, Arndt M, O’Shea A, Watt R, Hamilton J, Vincent K. Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload. BMC Nephrol. 2001;2:2. https://doi.org/10.1186/1471-2369-2-2
- ➢Kim YL, Biesen WV. Fluid overload in peritoneal dialysis patients. Semin Nephrol. 2017;37(1):43-53. https://doi.org/10.1016/j.semnephrol.2016.10.006
- ➢Morelle J, Marechal C, Yu Z, et al. AQP1 promoter variant, water transport, and outcomes in peritoneal dialysis. N Engl J Med. 2021;385(17):1570-1580. https://doi.org/10.1056/NEJMoa2034279 ★Essential Reading
- ➢Morelle J, Stachowska-Pietka J, Öberg C, et al. ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention. Perit Dial Int. 2021;41(4):352-372. https://doi.org/10.1177/0896860820982218K
- ➢Teitelbaum I. Ultrafiltration failure in peritoneal dialysis: a pathophysiologic approach. Blood Purif. 2015;39(1-3):70-73. https://doi.org/10.1159/000368972 ★Essential Reading
- ➢Trinh E, Perl J. The patient receiving automated peritoneal dialysis with volume overload. Clin J Am Soc Nephrol. 2018;13(11):1732-1734. https://doi.org/10.2215/CJN.02570218