Residency · Residency · Nephrology

Peritoneal Dialysis

Introduction

Peritoneal dialysis utilizes the peritoneal membrane as an endogenous dialysis membrane to achieve solute and water exchange between the blood in peritoneal capillaries and dialysate instilled into the peritoneal cavity. Although only approximately 11 percent of dialysis patients in the United States use peritoneal dialysis, utilization rates are considerably higher in many developing countries and in select European and Asian nations, where rates of 30 to 40 percent are not uncommon. The two principal modalities are continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). Peritoneal dialysis offers several advantages over hemodialysis, including home-based therapy, superior preservation of residual kidney function, generally better early quality of life, lower initial cardiovascular stress due to the absence of the hemodynamic fluctuations inherent to intermittent hemodialysis, and the avoidance of vascular access-related complications. Survival data suggest comparable outcomes to hemodialysis during the first two to three years of therapy, though technique survival is ultimately limited by peritonitis, progressive peritoneal membrane failure, and adequacy challenges.

Peritoneal Membrane Physiology

Membrane Structure

The peritoneal membrane has a total surface area of approximately 1 to 2 square meters, though the functional exchange area engaged in solute and water transport represents only a fraction of this total. Three anatomic barriers separate the peritoneal cavity from the blood: the mesothelium lining the peritoneal surface, the interstitium containing the peritoneal capillary bed, and the capillary endothelium itself. Effective solute and water exchange occurs primarily at the level of the peritoneal capillaries.

The three-pore model provides the most widely accepted framework for understanding peritoneal transport. Large pores, measuring 20 to 40 nm in diameter, permit the passage of macromolecules and proteins but are relatively few in number. Small pores, measuring 4 to 6 nm, account for the majority of solute transport and allow the passage of small solutes including urea, creatinine, and electrolytes. Ultra-small pores, corresponding to aquaporin-1 water channels with an effective diameter of less than 0.8 nm, transport free water exclusively and are impermeable to solutes. These aquaporin-mediated channels account for approximately 40 percent of ultrafiltration achieved with hypertonic glucose-based dialysate and are responsible for the phenomenon of sodium sieving, in which water crosses the membrane without sodium, transiently diluting the dialysate sodium concentration early in the dwell.

Peritoneal Equilibration Test (PET)

The peritoneal equilibration test is a standardized clinical tool used to characterize the transport properties of an individual patient's peritoneal membrane. The test is performed using a 4-hour dwell with 2 liters of 2.5 percent dextrose dialysate. Two key ratios are measured at the end of the dwell: the dialysate-to-plasma creatinine ratio (D/P creatinine) at 4 hours and the dialysate glucose at 4 hours relative to the initial dialysate glucose (D/D0 glucose).

Based on the D/P creatinine ratio, patients are classified into four transport categories. High transporters, with a D/P creatinine ratio greater than 0.81, achieve rapid equilibration of solutes across the membrane but also absorb glucose rapidly, losing the osmotic gradient and achieving poor ultrafiltration during long dwells. These patients are best suited to APD with short dwell times that capitalize on the early osmotic gradient before glucose absorption eliminates it. High-average transporters have a D/P creatinine ratio of 0.65 to 0.81 and represent the most common category. Low-average transporters, with ratios of 0.50 to 0.64, achieve slower solute clearance but maintain the osmotic gradient longer. Low transporters, with a D/P creatinine ratio below 0.50, have slow solute clearance but excellent sustained ultrafiltration due to minimal glucose absorption, making them ideal candidates for CAPD with long dwell times.

The PET should be performed 4 to 6 weeks after peritoneal dialysis initiation to allow the membrane to equilibrate after catheter insertion and the accompanying inflammatory response. Serial PETs performed over time are valuable for monitoring membrane integrity: an increasing transport rate over time suggests progressive peritoneal membrane deterioration, often driven by chronic glucose exposure and recurrent peritonitis, which may herald ultrafiltration failure and the eventual need to transition to hemodialysis.

<image>Diagram explaining the peritoneal equilibration test (PET) with two graphs. Graph 1: D/P creatinine ratio over time (0-4 hours) showing four curves representing high transporters (rapid rise to >0.81), high-average (0.65-0.81), low-average (0.50-0.64), and low transporters (slow rise to <0.50). Graph 2: D/D0 glucose ratio over time showing the inverse pattern - high transporters rapidly absorb glucose (low D/D0 at 4 hours), while low transporters maintain glucose gradient (high D/D0). Include a clinical interpretation table: high transporters = good clearance but poor UF, prescribe APD with short dwells; low transporters = poor clearance but good UF, prescribe CAPD with long dwells. Show the three-pore model inset with ultra-small pores (aquaporin-1, free water), small pores (solutes), and large pores (proteins).</image>

PD Modalities

Continuous Ambulatory Peritoneal Dialysis (CAPD)

Continuous ambulatory peritoneal dialysis involves 4 to 5 manual exchanges per day, each with a fill volume of 2 to 2.5 liters. Daytime dwells typically last 4 to 6 hours, while the overnight dwell extends to 8 to 10 hours. The peritoneal cavity contains dialysate at all times, providing continuous therapy without interruption. The advantages of CAPD include simplicity of technique, independence from machinery, and portability, allowing patients considerable freedom. The principal disadvantages are the multiple daily interruptions to the patient's routine and the peritonitis risk associated with each manual connection and disconnection.

Automated Peritoneal Dialysis (APD)

Automated peritoneal dialysis employs a cycler machine that performs multiple exchanges automatically during the night over a period of 8 to 10 hours. A typical prescription involves 4 to 6 cycles of 2 to 2.5 liters each. At the end of the overnight treatment, the patient may retain a last fill for a daytime dwell (known as a "wet day") to augment clearance and ultrafiltration, or the abdomen may be left empty during the day ("dry day") if ultrafiltration is adequate. APD reduces the number of connection events compared to CAPD, which may reduce peritonitis risk. It frees the patient during daytime hours, which is particularly advantageous for employed and school-age patients. APD is the preferred modality for high transporters because the short overnight dwell times exploit the early osmotic gradient before glucose absorption eliminates it. Disadvantages include being tethered to the cycler overnight, higher cost due to equipment and increased dialysate volumes, and the potential need for supplemental daytime exchanges if overnight clearance alone is insufficient.

Tidal PD

Tidal peritoneal dialysis is a variant of APD in which only a partial drain of 50 to 80 percent of the intraperitoneal volume is performed between cycles, maintaining continuous contact between dialysate and the peritoneal membrane. This approach theoretically improves clearance by eliminating the dead time during fill and drain phases, and it is particularly useful for patients who experience drain pain from complete drainage or who have poor drainage mechanics due to catheter malposition or omental wrapping.

PD Solutions

Glucose-Based Solutions (Standard)

Glucose-based solutions remain the most widely used peritoneal dialysate and are available in three concentrations: 1.5 percent, 2.5 percent, and 4.25 percent dextrose, corresponding to osmolalities of 347, 397, and 486 mOsm/kg, respectively. Ultrafiltration is directly proportional to the glucose concentration: the 1.5 percent solution provides minimal ultrafiltration, the 2.5 percent solution produces moderate ultrafiltration, and the 4.25 percent solution achieves maximal ultrafiltration of approximately 800 mL per exchange. However, 60 to 80 percent of the instilled glucose is absorbed systemically during each dwell, contributing to hyperglycemia, dyslipidemia, and weight gain. More insidiously, chronic glucose exposure drives the formation of advanced glycation end-products (AGEs) within the peritoneal membrane, promoting progressive membrane fibrosis and angiogenesis that ultimately lead to ultrafiltration failure. Standard glucose solutions also have a low pH of 5.2 to 5.5, required for heat sterilization of glucose, which impairs local peritoneal host defense mechanisms.

Icodextrin (Extraneal)

Icodextrin is a glucose polymer with a molecular weight of approximately 16,000 Daltons that functions as an iso-osmolar colloid. Unlike crystalloid glucose solutions that generate ultrafiltration through crystalloid osmosis, icodextrin induces ultrafiltration via colloid osmotic pressure acting through the small pores of the peritoneal membrane. This mechanism produces sustained ultrafiltration over 12 to 16 hours, making icodextrin ideal for the long dwell: the overnight dwell in CAPD or the daytime dwell in APD. Icodextrin is absorbed via peritoneal lymphatics at a rate of approximately 40 percent over 12 hours and is metabolized to maltose and maltotriose.

A critically important drug interaction must be recognized: icodextrin metabolites interfere with glucose monitoring strips that use the glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ) method, producing falsely elevated glucose readings that can mask true hypoglycemia. Patients using icodextrin must use glucose oxidase-based monitoring strips. Icodextrin is typically prescribed for one long dwell per day, not for all exchanges. Its particular value lies in achieving superior ultrafiltration in high transporters, who rapidly absorb crystalloid glucose, and in reducing overall glucose exposure in diabetic peritoneal dialysis patients.

Amino Acid-Based Solutions (Nutrineal)

Amino acid-based solutions contain a 1.1 percent amino acid mixture that provides approximately 20 grams of protein supplementation per 2-liter exchange while generating ultrafiltration comparable to 1.5 percent glucose. This dual benefit makes amino acid solutions particularly attractive for malnourished peritoneal dialysis patients, a population at significant risk for poor outcomes. However, use is limited to one exchange per day because excessive amino acid loading can exacerbate metabolic acidosis.

Biocompatible Solutions

Biocompatible peritoneal dialysis solutions are characterized by neutral pH and low glucose degradation product (GDP) content. They employ multi-chamber bag technology that keeps glucose at low pH in a separate compartment until the bag is activated and the chambers are mixed immediately before infusion, resulting in a physiologic pH in the delivered solution. Available products include Balance, Physioneal, and BicaVera. The balANZ trial demonstrated higher preservation of residual renal function with biocompatible solutions, and there is theoretical evidence that reduced GDP exposure may preserve peritoneal membrane function over time, potentially extending technique survival.

PD Adequacy

Targets (KDOQI/ISPD)

Peritoneal dialysis adequacy is assessed by total weekly Kt/V urea, which represents the sum of peritoneal clearance and residual renal clearance. Current KDOQI and ISPD guidelines recommend a target weekly Kt/V of at least 1.7. The weekly creatinine clearance, previously used as an independent adequacy marker, was dropped from guideline recommendations beginning in 2006 as evidence emerged that it did not independently predict outcomes.

Residual renal function is the dominant contributor to overall clearance and outcomes in peritoneal dialysis patients. The CANUSA study initially appeared to demonstrate a survival benefit with higher total clearance, but reanalysis revealed that the survival advantage was driven entirely by residual renal function rather than peritoneal clearance per se. The ADEMEX trial provided further clarity by randomizing patients to increased peritoneal clearance versus standard clearance and demonstrating no survival benefit from increasing peritoneal Kt/V above 1.7. These landmark studies underscore that adequacy targets should not be interpreted in isolation; clinical assessment of volume status, nutritional parameters, phosphorus control, and uremic symptom burden are equally important determinants of patient well-being.

Preserving Residual Renal Function

Given the critical importance of residual renal function to peritoneal dialysis outcomes, its preservation is a clinical priority. Even a small amount of residual urine output, corresponding to 1 mL/min of residual clearance, is equivalent to approximately 10 liters per week of creatinine clearance, an amount that would be extremely difficult to achieve through peritoneal clearance alone. Strategies for preserving residual kidney function include avoiding nephrotoxins such as NSAIDs and aminoglycosides, continuing ACE inhibitors or ARBs which may slow residual function decline, using biocompatible peritoneal dialysis solutions, and avoiding intravascular volume depletion from excessive ultrafiltration. Residual renal function should be monitored every one to two months with 24-hour urine collections for volume and creatinine clearance.

Complications

Peritonitis

Peritonitis is the most common serious complication of peritoneal dialysis and remains the leading cause of technique failure and transfer to hemodialysis. The ISPD 2022 guidelines set a target peritonitis rate of fewer than 0.5 episodes per patient-year. The classic presentation consists of cloudy dialysate with an effluent white blood cell count exceeding 100 cells per cubic millimeter with greater than 50 percent neutrophils, accompanied by abdominal pain and, in some cases, fever.

Diagnosis requires collection of effluent for cell count with differential, Gram stain, and culture. Proper culture technique is essential: 5 to 10 mL of effluent should be inoculated into blood culture bottles and incubated for at least 72 hours, as standard plate cultures have significantly lower sensitivity. The most common causative organisms are coagulase-negative staphylococci (approximately 30 percent), Staphylococcus aureus (approximately 15 percent), streptococcal species (approximately 10 percent), gram-negative organisms (approximately 20 percent), culture-negative episodes (approximately 15 percent), and fungal organisms (3 to 5 percent).

Peritonitis Treatment (ISPD 2022)

Empiric antibiotic therapy must cover both gram-positive and gram-negative organisms and should be initiated intraperitoneally in the next exchange after effluent samples are collected. The recommended empiric regimen consists of intraperitoneal cefazolin (or vancomycin if MRSA prevalence is high in the institution) combined with intraperitoneal ceftazidime (or gentamicin). Intermittent dosing in a single exchange per day is as effective as continuous dosing: cefazolin at 15 to 20 mg/kg, ceftazidime at 15 to 20 mg/kg, and vancomycin at 30 mg/kg with repeat dosing every 5 to 7 days guided by serum trough levels.

At 48 to 72 hours, the antibiotic regimen should be narrowed based on culture and sensitivity results. Treatment duration depends on the organism: 14 days for coagulase-negative staphylococci and 21 days for Staphylococcus aureus, gram-negative organisms, and enterococci. Catheter removal is indicated in several circumstances: refractory peritonitis, defined as failure to improve after 5 days of appropriate antibiotics; relapsing peritonitis, defined as recurrence with the same organism within 4 weeks of completing therapy; fungal peritonitis, which mandates immediate catheter removal regardless of clinical appearance; fecal peritonitis suggestive of bowel perforation; tunnel infection concurrent with peritonitis; and mycobacterial peritonitis. Fungal peritonitis deserves particular emphasis: the catheter must be removed immediately upon culture confirmation, and antifungal therapy with fluconazole or an echinocandin should be administered for 2 to 4 weeks. A minimum of 2 weeks of hemodialysis support should elapse before attempting peritoneal dialysis restart with a new catheter.

Exit Site and Tunnel Infections

Exit site infections present with purulent drainage from the catheter exit site. Erythema alone without purulence does not constitute an exit site infection but warrants close monitoring. Treatment consists of topical mupirocin for suspected Staphylococcus aureus infections and oral antibiotics tailored to the organism: cephalexin for gram-positive infections and fluoroquinolones for gram-negative or Pseudomonas infections. Tunnel infections manifest as tenderness and erythema along the subcutaneous tunnel tract and frequently require catheter removal, especially when concurrent with peritonitis. Prevention of exit site infections is a cornerstone of peritoneal dialysis care: the HONEYPOT trial demonstrated that topical mupirocin application to the exit site reduced Staphylococcus aureus exit site infections, and daily exit site care with either mupirocin or gentamicin cream is now recommended by ISPD guidelines.

<image>Management algorithm for peritoneal dialysis peritonitis. Start with clinical suspicion: cloudy effluent, abdominal pain, fever. Immediate steps: collect effluent sample (cell count, differential, Gram stain, culture in blood culture bottles), begin empiric IP antibiotics in the NEXT exchange (cefazolin/vancomycin + ceftazidime/gentamicin). At 48-72 hours: review culture results. Branch based on organism: (1) Gram-positive (CoNS, S. aureus): narrow to cefazolin or vancomycin for 14-21 days. (2) Gram-negative (single organism): narrow based on sensitivities for 21 days; consider catheter removal if Pseudomonas. (3) Culture-negative at 72 hours: continue empiric therapy, re-culture, consider unusual organisms (TB, fungi). (4) Fungal: IMMEDIATE catheter removal + antifungal for 2-4 weeks. (5) No improvement at day 5: refractory peritonitis → catheter removal. Include a panel showing catheter removal indications: refractory (no response day 5), relapsing (same organism <4 weeks), fungal, fecal/bowel perforation, tunnel infection + peritonitis.</image>

Encapsulating Peritoneal Sclerosis (EPS)

Encapsulating peritoneal sclerosis is a rare but devastating complication characterized by progressive peritoneal fibrosis that leads to encapsulation and entrapment of the bowel, causing chronic or recurrent intestinal obstruction. The risk increases substantially with prolonged peritoneal dialysis duration beyond 5 years, recurrent peritonitis episodes, and chronic exposure to high-glucose dialysate. Beta-blocker use has been proposed as an additional risk factor, though this association remains controversial. Patients present with recurrent episodes of bowel obstruction, weight loss from nutritional compromise, bloody effluent, and progressive loss of ultrafiltration capacity. Computed tomography demonstrates peritoneal thickening and calcification, bowel tethering, and the characteristic "cocoon" appearance of encased bowel loops. Treatment options are limited and carry high morbidity: surgical enterolysis to free adherent bowel loops, tamoxifen for its antifibrotic properties based on limited evidence, and corticosteroids. Transfer to hemodialysis is mandatory. Mortality remains high, ranging from 25 to 55 percent, underscoring the importance of prevention through glucose-sparing strategies and timely transition to hemodialysis in patients with progressive membrane deterioration.

Mechanical Complications

Catheter malposition and migration are common mechanical complications, often caused by omental wrapping around the catheter tip or fibrin occlusion of the catheter lumen. Dialysate leaks can manifest in several ways: inguinal hernias from increased intra-abdominal pressure, peritoneal-pleural leaks causing hydrothorax, and pericatheter exit site leaks, particularly in the early postoperative period. Hydrothorax classically presents as a right-sided pleural effusion, reflecting the predominant lymphatic connections through the right hemidiaphragm, and is diagnosed by demonstrating high glucose concentration in the pleural fluid relative to serum. Treatment options include pleurodesis, temporary cessation of peritoneal dialysis, or permanent transfer to hemodialysis.

Key Clinical Pearls

• The PET classifies membrane transport and directs PD modality selection: high transporters do best with short-dwell APD; low transporters with long-dwell CAPD
• Residual renal function is the strongest predictor of PD patient survival; aggressively preserve RRF with biocompatible solutions, ACEi/ARB, and nephrotoxin avoidance
• Icodextrin provides sustained UF over long dwells without glucose exposure; essential for high transporters and diabetic patients; remember to use glucose oxidase-based glucometers (maltose interference)
• Fungal peritonitis requires IMMEDIATE catheter removal regardless of clinical response; failure to remove the catheter is associated with high mortality
• PD adequacy targets (Kt/V >=1.7) should not be interpreted in isolation; clinical assessment of volume status, nutrition, and uremic symptoms is equally important; ADEMEX showed no benefit of increasing Kt/V above the minimum

References

1. Li PKT, Chow KM, Cho Y, et al. ISPD Peritonitis Guideline Recommendations: 2022 Update on Prevention and Treatment. Perit Dial Int. 2022;42(2):110-153.
2. Paniagua R, Amato D, Vonesh E, et al. Effects of Increased Peritoneal Clearances on Mortality Rates in Peritoneal Dialysis (ADEMEX). J Am Soc Nephrol. 2002;13(5):1307-1320.
3. Johnson DW, Mudge DW, Sturtevant JM, et al. A Randomized Controlled Trial of Topical Exit Site Mupirocin Application in Patients with Tunnelled, Cuffed Haemodialysis Catheters (HONEYPOT). Nephrol Dial Transplant. 2002;17(10):1802-1805.
4. Twardowski ZJ. Clinical value of standardized equilibration tests in CAPD patients. Blood Purif. 1989;7(2-3):95-108.
5. Brown EA, Bargman JM, van Biesen W, et al. Length of Time on Peritoneal Dialysis and Encapsulating Peritoneal Sclerosis - Position Paper for ISPD. Perit Dial Int. 2017;37(4):362-374.

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