Dextrose, the primary osmotic agent in peritoneal dialysis (PD) solutions, is available in varying concentrations. In North America, solutions are labeled with the monohydrate molecular weight (MW 198 Da), offering 1.5%, 2.5%, and 4.25% options. In Europe, they are labeled by the anhydrous dextrose content (MW 180) as 1.36%, 2.27%, and 3.86%. These represent low, intermediate, and high-concentration classes, respectively. Higher dextrose concentration solutions are used to achieve greater UF volume, particularly in patients with volume overload. Simulations by computer modeling have demonstrated that during a 12-hour dwell time, the most significant UF occurs early on, driven by a pronounced osmotic gradient ( Fig. 63.2 ). This UF volume progressively decreases as the gradient weakens, leading to fluid being absorbed through small pores and lymphatics in the adjacent tissues. There is also a specialized 0.5% concentration solution that exists for patients who need intravascular volume expansion, but its use is confined to a handful of countries, limiting its broader application. This low-concentration solution can assist in the transfer of water and electrolytes from the dialysate back into the bloodstream, sometimes obviating the need for intravenous fluid support.

(A) Computer model depicting ultrafiltration (UF) across the peritoneal membrane using a 3.86% glucose solution demonstrates that, following the dissipation of the osmotic gradient at 240 minutes, fluid reabsorption occurs via small pores and lymphatic pathways.

Due to the correlation of solute transport with the area of small pores, membranes with higher transport capabilities absorb more fluid. (B) The ultrafiltration volume (UFV) over time is represented for different glucose concentrations: 3.86% (yellow), 2.27% (green), and 1.36% (blue), using a three-pore model simulation. (C) The graph shows a comparison between the ultrafiltration profile for 7.5% icodextrin (blue line) and a 3.86% glucose solution (red line), both simulated with the three-pore model. (D) Variations in UF are observed for different peritoneal membrane solute transfer rates using a 2 L 2.5% dextrose solution. Patients with rapid solute transfer rates in their peritoneal membranes experience reduced maximum UF and a quicker onset of fluid reabsorption.

Adapted with permission from [A], [C], and [B and D].

While effective, the long-term use of dextrose-based solutions presents various challenges. One significant issue is that sustained glucose absorption can lead to metabolic complications, such as hyperglycemia, hyperinsulinemia, and dyslipidemia (see “ Non–Catheter-Related Complications ,” “ Metabolic Complications ”). Moreover, the osmotic gradient, which powers the UF process, tends to diminish over time. This is particularly notable during prolonged dwell times, as seen in CAPD during the day or overnight with APD. Given these drawbacks and earlier mentioned challenges with glucose degradation product (GDP) generation following heat sterilization, there had been a push to develop alternative solutions. Options under consideration included PD solutions with a more stable osmotic agent suitable for extended dwell times or dextrose-based solutions engineered to minimize the formation of GDPs. The primary aim was to maintain the efficacy of treatment while mitigating its long-term drawbacks.

Lactate has been the traditional primary buffer used in PD solutions; however, the advancement of multichambered systems using bicarbonate as a buffer has provided a viable alternative. These systems store dextrose and buffer separately and combine them immediately before use. The multichambered design prevents the precipitation of calcium and magnesium with bicarbonate that could occur within the PVC bags with routine storage of solutions. Additionally, this innovation minimizes the generation of GDPs and enables the use of other buffers, such as bicarbonate, which is more physiologic. As a highly reactive substance, glucose readily breaks down into GDPs, which can lead to the formation of early or advanced glycation end products (AGEs). Various studies have demonstrated that exposure to GDPs may be associated with increased synthesis of vascular endothelial growth factor, mesothelial denudation, and induction of profibrotic cytokines, which in turn lead to changes in the peritoneal membrane that affect the efficiency of small solute and water transport. The production of GDPs is influenced by factors such as pH, temperature, and time, particularly when PD solutions undergo heat sterilization. As a result of the aforementioned hazards of GDPs, there has been growing interest for more “biocompatible” solutions, described briefly as follows.

The multichambered, or low GDP neutral pH, solutions had been proposed as an alternative to overcome some of the limitations of traditional lactate-buffered solutions. They offer a more neutral pH, potentially reducing the discomfort associated with infusion. They also enable the use of heat sterilization methods that are less likely to produce harmful GDPs. However, the clinical benefits of these newer solutions have been a subject of debate.

The efficacy and safety of biocompatible solutions remain topics of contention. The balANZ study, a randomized controlled trial (RCT), reported that the use of low GDP neutral pH solutions resulted in a decreased incidence of peritonitis compared with those using conventional solutions. However, subsequent RCTs have produced varied findings, leading to uncertainties about the true clinical advantages of these biocompatible solutions. Despite a Cochrane review of 15 studies involving 835 patients showing significant preservation of residual kidney function with the use of neutral pH, low-GDP PD solutions, its widespread adoption is still limited, underscoring the ongoing controversy in this area. Overall, systematic reviews have offered inconclusive evidence about the overarching benefit of low GDP neutral pH solutions in PD. ^, As a result, these solutions are now often reserved for patients experiencing infusion pain with conventional solutions. These solutions may also lead to better preservation of peritoneal membrane function compared with lactate-buffered solutions. While low GDP solutions may offer many benefits, studies in pediatric patients have shown they can still induce early peritoneal inflammation, fibroblast activation, and angiogenesis, which affect membrane transport function.

Electrolytes, specifically sodium, calcium, magnesium, and chloride, are fundamental to PD solutions. Standard PD solutions have slightly lower sodium concentrations than those used for HD, which facilitates diffusive sodium removal. Although preliminary findings suggest that reducing sodium concentration in dialysate could enhance sodium removal by increasing the sodium gradient between blood and dialysate, these promising results have yet to translate into changes in clinical practice, as no definitive benefits from using low-sodium PD solutions have been documented to date.

In recognizing the shortcomings of dextrose-based solutions, attention had shifted toward other osmotic agents, namely amino acids and icodextrin. Icodextrin, an iso-osmolar glucose polymer with an osmolality of approximately 280 mOsm/L, is offered as a 7.5% solution. It shares an electrolyte profile with dextrose-based solutions. Its molecular weight, which ranges between 13 and 19 kDa, coupled with its oncotic effect, significantly amplifies the osmotic efficiency of the solution, outperforming dextrose-based alternatives. This characteristic leads to prolonged UF over 12 hours, making icodextrin especially suited for extended dwell exchanges. For example, it is preferred for daytime dwells in patients on APD and nighttime dwells for CAPD, as its large size prevents crossing the peritoneal membrane, thus maintaining a prolonged oncotic effect across the membrane.

Currently, icodextrin is approved for once-daily administration. However, some observational studies hint that administering it twice daily can be beneficial for certain patients. Additionally, meta-analytic data have demonstrated that icodextrin may improve peritoneal UF and reduce risk of volume overload in patients. An essential point for medical professionals to note is the potential for maltose buildup in the extracellular compartment when using icodextrin. This accumulation can trigger a shift of water from the intracellular space, resulting in mild hyponatremia. Although the body can gradually absorb and metabolize icodextrin into maltose, there is no documented maltose-related toxicity. Nonetheless, maltose can interfere with specific assays used for blood glucose measurements, yielding inaccurately high glucose readings. Therefore when treating patients with icodextrin, it is important to consider alternative blood glucose monitoring methods or ensure that the chosen glucometer is compatible with icodextrin and does not misinterpret maltose as glucose.

Amino acid–based PD solutions were developed to counteract protein-energy malnutrition, a prevalent challenge for patients on dialysis. ^, Amino acid–based solutions are primarily used for patients suffering from inability to maintain consistent enteral protein intake or who suffer from severe malnutrition or in situations demanding strict metabolic control. They serve as a nutritional supplement in these select cases while also offering the added advantage of minimizing the overall exposure of dextrose to the peritoneal membrane. These solutions contain a 1.1% amino acid blend, mirroring the osmolality seen in a 1.36% dextrose solution. While amino acid dialysate solutions can be used to enhance nutrition, particularly in high-risk patients, observational data have not found a significant impact on patient survival. As a result, their effectiveness in real-world scenarios has unfortunately fallen short of expectations. Due to potential risks including acidosis and elevated plasma urea levels from absorbed amino acids, their use is restricted to a single exchange per day. Presently, these solutions are available in some centers around the globe and are primarily used for glucose-sparing purposes.

Studies exploring dextrose-free PD solutions, particularly those using l -carnitine and xylitol, have shown encouraging outcomes and clinical trials are under way. Initial observations indicate a favorable safety profile, alongside efficient solute removal and effective peritoneal ultrafiltration. These preliminary results suggest potential benefits in the management of PD patients and underscore the need for more extensive, controlled trials to confirm their clinical efficacy and safety.

Catheter-related complications in PD can have a significant impact on patient quality of life and overall effectiveness of therapy. The early identification and prompt management of these complications may reduce the likelihood of a premature transition to HD. Many non-infectious catheter-related complications are predominantly related to flow dysfunction. Flow dysfunction in PD is multifactorial and can be further categorized into one-way or two-way obstruction. Two-way obstruction can be attributed to the suboptimal evacuation of the dialysate fluid, due to visceral structures within the pelvic anatomy interacting with the catheter tip and covering the apertures along the distal intraperitoneal segment. This obstruction can occur due to extrinsic compression (due to omentum) or kinking of the catheter itself, intraluminal obstruction, and catheter entrapment. ^,

PD catheter entrapment, a notable and concerning complication, arises predominantly when the catheter is ensnared within the omental matrix or tethered by intraperitoneal adhesions. It can also occur with other structures in the pelvis, and there have been documented reports of fallopian tube entrapment leading to flow dysfunction in the literature. ^, This phenomenon leads to occlusion of the holes along the side of the catheter, manifesting as either unidirectional or bidirectional flow dysfunction. Regardless of the type of entrapment, it usually requires advanced laparoscopic intervention to allow for a release of the entrapment or exchange for a new PD catheter. Patients with suspected entrapments should not have the catheter exchanged blindly or use a percutaneous approach as there is significant risk for visceral and organ injury without direct visualization.

On the other hand, extrinsic compression is a type of dysfunction that often emerges because of pathophysiologic conditions such as bladder distension or constipation. Constipation is often identified as a leading cause of one-way outflow obstruction due to the pressure exerted by the distended colon, impeding the patency of the catheter by obstructing the apertures on the distal end. The diagnostic workup for this condition typically involves an abdominal radiograph to assess significant fecal loading and catheter-tip position. Management in such cases often depends on the underlying cause but usually requires treatment with a laxative regimen to relieve the obstructive effect on the catheter. It should be important to recognize that excessive external compression in some cases can result in two-way obstruction in PD catheters.

On another note, a significant subset of PD catheter flow dysfunction emanates from intraluminal obstructions. These obstructions, which manifest as impediments to both the instillation and drainage phases of PD, can arise from mechanical kinks or intraluminal debris such as fibrin. The development of fibrin is commonly seen after an inflammatory process such as peritonitis or even after a catheter is newly inserted. The therapeutic approach for this complication is a stepwise approach of irrigating the catheter with saline flushes and a combination of intraluminal heparin or tissue plasminogen activators when fibrin is suspected. In cases where flow remains obstructed despite the aforementioned interventions, imaging may be warranted to rule out any catheter kinks. In cases where catheter kinks are absent, fluoroscopic-guided manipulation may be required to restore catheter luminal patency. ^, Additionally, a small single-center Canadian observational study suggested that fluoroscopic manipulation of catheters may also be considered in cases where conservative approaches to restore function have been ineffective. However, the success rate of fluoroscopic manipulation for catheters that have migrated to the upper abdomen or have primary failure is relatively low, due to significant anatomic issues like omental wrapping and compartmentalization by adhesions.

Metabolic complications in PD are primarily associated with systemic glucose absorption. This absorption may contribute 400 to 1200 kcal/day and can lead to hyperglycemia. Managing hyperglycemia can be challenging for patients on dialysis. Although biguanides are contraindicated for patients with advanced kidney disease, other antiglycemic agents including certain sulfonylureas and glucagon-like peptide 1 receptor agonists can be used in clinical practice. Despite the theoretical benefits of SGLT2 inhibitors in preserving residual kidney function and reducing peritoneal fibrosis, there are limited data to date on safety and efficacy within the PD population, and SGLT2 inhibitors lose their hypoglycemic efficacy as GFR drops below approximately 45 mL/min/1.73 m ² . Intraperitoneal insulin offers convenience for patients but may increase the risk of bacterial contamination with injection of dialysate bags and focal hepatic steatosis. As a result, the subcutaneous administration of insulin is the preferred method for patients on PD who require insulin.

The IMPENDIA (Improved Metabolic control of Physioneal, Extraneal, Nutrineal [P-E-N] vs. dianeal only in DIAbetic CAPD and APD patients) randomized trial underscored that while glucose-sparing treatments in patients on PD with diabetes enhance metabolic outcomes—manifested by lowered HbA1c, VLDL cholesterol, triglycerides, and apolipoprotein B—there is a notable rise in adverse events, likely linked to volume overload. This includes a marked decrease in serum albumin and a higher incidence of serious adverse events and mortality in the glucose-sparing group, underscoring the need for vigilant fluid volume status monitoring with such regimens.

Patients on PD often show higher levels of total and LDL cholesterol, apolipoprotein B, lipoprotein (a), and triglycerides and lower levels of high-density lipoprotein cholesterol compared with those on HD, possibly due to systemic glucose absorption and peritoneal protein losses. While statins can safely lower serum cholesterol in patients on dialysis, their effectiveness in reducing cardiovascular mortality is not yet proven. The Study of Heart and Renal Protection (SHARP), which included patients receiving PD, found a reduced risk of cardiovascular events with simvastatin-ezetimibe treatment but no significant effect on cardiovascular mortality and an attenuated benefit in patients on dialysis relative to those with non–dialysis-requiring CKD. Further research is needed to understand the efficacy of statins in reducing the risks of cardiovascular events and mortality in patients receiving dialysis, especially those on PD where data are particularly scarce.

Patients frequently exhibit disorders of mineral metabolism while on PD. Hypercalcemia can arise due to treatment with calcitriol or active vitamin D analogs, calcium-rich dialysate solutions, or calcium-based phosphate binders. ^, Hypercalcemia may reflect the underlying cause of end-stage kidney disease, such as multiple myeloma or less commonly sarcoidosis, or more commonly can reflect low turnover bone disease. Strategies to mitigate the risk of hypercalcemia include the use of lower calcium concentrations in dialysate along with noncalcium phosphate binders. Hyperphosphatemia can be associated with mortality, cardiovascular events, and fractures in patients receiving dialysis including those on PD. Typically, hyperphosphatemia is less severe in patients on PD relative to those on hemodialysis, in part owing to better preservation of residual kidney function. Non–calcium-based phosphate binders may be particularly well suited for patients on PD, as calcium-based binders tend to cause constipation and patients on PD. Ferric citrate is among the more potent intestinal phosphate binders and can serve as an iron supplement, potentially abrogating the need for intravenous iron supplementation to support erythropoiesis. Control of hyperphosphatemia may be improved by the addition of the phosphate absorption inhibitor tenapanor, a sodium-hydrogen exchanger 3 inhibitor, which reduces passive intestinal phosphate absorption, and can result in softening of stools.

Patients on PD are at an increased risk of developing hypokalemia due to the nature of potassium-free dialysate solutions, which enhances the diffusive gradient for its clearance. Additionally, patients will also achieve convective clearance, particularly in the presence of large UF volumes, a phenomenon referred to as solvent drag. Hypokalemia frequently occurs in patients with inadequate nutrition and is exacerbated by high doses of loop diuretics (with or without thiazides) prescribed to patients with residual kidney function. In terms of management, patients can typically normalize serum potassium concentrations by liberalizing diets typically recommended for patients with kidney failure, particularly by increasing intake of potassium-rich fruits and vegetables, which not only constitute excellent sources of dietary potassium but can provide additional dietary fiber, often aiding in the prevention of constipation. For patients with hypokalemia unwilling or unable to materially increase dietary potassium intake, oral potassium supplements can be added to the medication regimen. In a randomized trial from Thailand with 167 participants, it was found that, compared with reactive potassium supplementation at serum levels below 3.5 mEq/L, a protocol-driven oral potassium regimen aiming to keep serum potassium between 4 and 5 mEq/L could lower the risk of peritonitis in PD patients with hypokalemia. This underscores the importance of managing hypokalemia in this population. Patients with hypokalemia on PD should not be managed with the addition of potassium to the dialysate solutions due to increased risk of contamination and peritonitis. Hyperkalemia is rarer, often due to factors like renin-angiotensin system blockade or dietary excess, and is typically mild if dialysis is consistent.

Hyponatremia is another common electrolyte abnormality seen in PD, often the result of excessive water intake. Hyponatremia may also be associated with malnutrition (hypoosmolar). ^, Certain cases of hyponatremia (hyperosmolar) may arise secondary to hyperglycemia or icodextrin administration, inducing a hyperosmolar state. Additionally, in the context of severe malnutrition, a hypoosmolar variant of hyponatremia can manifest. ^, Hypernatremia is rare but can occur in older patients with reduced thirst sensation or limited water access. Intense and frequent dialysis using hypertonic dialysate might cause hypernatremia through sodium sieving, a concept discussed in earlier sections. Hypernatremia due to sodium sieving can be prevented by incorporating longer dwell periods in the 24-hour dialysis cycle to facilitate sodium-coupled fluid removal.

Hypomagnesemia has been linked with poorer nutritional status, suggesting that malnutrition may be a significant contributor. Additionally, observational data have suggested that frequent use of hypertonic dialysate solutions may also lead to hypomagnesemia in patients on PD.

Hydrothorax complicates PD with an estimated incidence between 1.6% and 10%. ^, Hydrothorax occurs when dialysate fluid from the intraperitoneal cavity enters the pleural space as a result of pleuroperitoneal communication, with the majority of cases occurring on the right side. The prevailing theory is that most pleuroperitoneal leaks occur on the right side due to a congenitally porous diaphragm, with the liver functioning as a piston and the ascending colon exerting upward peristaltic motion, driving fluid through these openings. Patients may present with dyspnea and, in more severe instances, respiratory distress with associated lung collapse. However, approximately 25% of patients present with no symptoms and hydrothorax is identified incidentally on imaging. Although the underlying mechanism by which the dialysate fluid enters the pleural space is thought to be related to pleuroperitoneal communication as mentioned earlier, increases in IAP can also play a significant role.

In terms of diagnostic evaluation, chest radiograph commonly identifies hydrothorax and should be performed with patients in a lateral decubitus position, which is useful in ensuring that the associated pleural effusion is not loculated. Patients presenting with symptomatic PD hydrothorax may benefit from therapeutic thoracentesis. Diagnostic thoracentesis allows for fluid analysis, which may reveal transudative effusions associated with a high glucose concentration and extremely low protein levels. However, in cases where a non–dextrose-based solution is used, such as icodextrin, glucose concentrations in the effusion will be similar to that of the plasma. Additionally, glucose concentrations in a chronic pleural effusion may be low due to pleural glucose absorption. As a result, the absence of elevated glucose in a pleural effusion does not rule out pleuroperitoneal leak. Another diagnostic tool that had been historically employed was the instillation of methylene blue into the peritoneal cavity, which would subsequently appear in the pleural fluid. However, this approach has fallen out of favor due to an increased risk of chemical peritonitis with methylene blue use in the peritoneal cavity. Another noninvasive approach in centers equipped with the appropriate resources is the use of peritoneal scintigraphy. This uses technetium-99m labeled albumin added to dialysate solution, and the patient is evaluated using a gamma camera to determine if any of the labeled albumin is identified in the pleural cavity. A computed tomography (CT) peritoneogram (see hernia section for details) can also be used but may lead to inconclusive results, especially if the pleuroperitoneal defect is small, not allowing for dispersion of iodinated contrast to be seen in the pleural space. The CT peritoneogram uses the presence of iodinated contrast in the dialysate. To increase the diagnostic sensitivity of this study, patients should have fluid dwell for at least 2 to 3 hours or as long as possible to allow for dispersion of fluid through any defects that may be present.

Though there are some reports of temporary cessation of PD resulting in healing of the hydrothorax, definitive management of a PD hydrothorax is often required. This entails closure of the existing pleuroperitoneal communication using video-assisted thoracoscopic surgery (VATS) to allow for surgical correction of diaphragmatic defects coupled with the use of a sclerosing agent for targeted pleurodesis. VATS allows direct visualization of possible diaphragmatic defects and can lead to greater success in preventing recurrence of PD hydrothorax. However, patients will typically require respite of several weeks from PD to allow for effective healing of closures. In cases where surgical closure of pleuroperitoneal communication is not feasible, an attempt at bedside pleurodesis may be warranted; otherwise, the patient is likely to require transition to HD.

Practitioners should also be familiar with another important complication in the form of pericatheter leaks. These leaks usually occur as an early complication after catheter insertion or manipulation but could also happen at any point while on PD. Additionally, ports used during advanced laparoscopic insertion may also be sources of leaks that should be considered. An early sign of a pericatheter leak is the presence of reduced UF volumes, followed by progressive weight gain with swelling in the abdominal subcutaneous tissues or genital areas. Many of these leaks can be managed supportively by adjusting PD therapy with reduced fill volumes in a supine position. However, if leaks are persistent despite these approaches, then additional imaging in the form of CT peritoneogram may be considered to determine if any sources of the leak require surgical correction.

Genital edema in patients on PD is a significant complication. It typically arises when dialysate travels through a patent processus vaginalis, leading to hydrocele and potential scrotal or labial wall edema, or via an abdominal wall defect near the catheter tract, causing edema in the genital area. To identify the path of the leak, a CT peritoneogram is recommended to distinguish between fluid tracking through a patent processus vaginalis (indirect hernia) or an abdominal wall defect (direct hernia). Treatment requires stopping PD, with bed rest and scrotal elevation as supportive measures. APD performed in a supine position with low fill volumes and no daytime dwell can effectively lower IAP and prevent the recurrence of leaks. If leaks persist, transitioning to HD may be necessary, either as a temporary or permanent measure, based on the feasibility of surgically repairing the leak sources. Additionally, if there is a patent processus vaginalis, then definitive surgical repair is required to close the defect, as explained in the next section.

Patients receiving PD are at an increased risk of developing hernias due to elevations in IAP. IAP is influenced by age, body size and composition, sitting position, dialysate volume, and prior abdominal surgery. Other risk factors for hernia development include female patients and those with a diagnosis of polycystic kidney disease. The IAP is highest when a patient sits, decreases when a patient stands, and is lowest when he or she is supine. Observational data indicate that umbilical and inguinal hernias are the most common types encountered in patients on PD. Many of these hernias, particularly in the inguinal or periumbilical areas, predate initiation of PD but become more pronounced due to increased IAP from the volume of intraperitoneal dialysate. Additional data have noted that about 10% to 25% of patients on PD will eventually develop hernia(s) during their time on therapy. ^, New hernias can also emerge in different areas including the site of catheter insertion.

Treatment of hernias varies and depends on the type of hernia. While most hernias require surgical intervention, a conservative approach might be reasonable for certain patients, especially older patients including those too frail for surgery. Small hernias have a high risk of bowel incarceration and should be repaired surgically. If a hernia is surgically repaired, it is imperative to have PD prescriptive strategies to reduce intraabdominal pressure, which may decrease the likelihood of recurrence. Patients may require a period of about 3 to 4 weeks to allow for effective healing. If a patient does not have significant residual kidney function, he or she may require a brief transition to HD to allow healing after surgery. In patients with ample residual kidney function, an alternative approach to consider would be temporary (i.e., 48-hour holding of PD in the immediate postoperative period) followed by low-volume exchange supine PD. The use of mesh in hernia repairs is generally preferred to minimize recurrence risk, but the decision to employ mesh depends on the hernia type, location, along with the judgment and expertise of the surgeon. Location of the mesh exposed to the peritoneal surface may preclude the use of bridging HD with the need for a 4- to 6-week period of peritoneal healing at the mesh site, though in most cases repair can be achieved with deeper mesh placement.

Encapsulating peritoneal sclerosis (EPS) is a rare yet severe complication seen in patients who have been on PD for a prolonged period. Historically, the incidence rate varied from 1.4 to 13.6 cases per 1000 patient-years around the globe but now is much less common, as highlighted in the 2017 ISPD position paper. In this position paper, the ISPD emphasized that most patients undergoing long-term PD do not experience EPS with current data reporting an incidence between 0.7 and 9.5 episodes per 1000 patient-years. In EPS, the peritoneal membrane undergoes significant sclerosis, causing the intestines to become encased or “cocooned,” leading to major disruptions in intestinal function including major motility disorders. As a result, patients may develop a myriad of gastrointestinal symptoms and complications including nutrient malabsorption, intestinal obstruction, fluid accumulation in the abdomen, appetite loss, and progressive weight decline. Patients often exhibit systemic inflammation marked by mild fever, low serum albumin concentrations, and increased inflammatory cytokines including tumor necrosis factor–α and interleukin 6. ^{, , ,} The diagnosis of EPS requires signs of intestinal obstruction combined with evidence of bowel encapsulation, which can be determined through methods like CT scans or pathologic examinations. CT scans are particularly reliable for making the diagnosis in a variety of clinical scenarios with available CT scoring systems for EPS diagnosis. However, if a patient undergoes surgery, pathologic confirmation becomes possible but extra caution is essential during surgical procedures to avoid the risk of bowel perforation.

Although the exact cause of EPS remains unknown, several contributing factors have been identified and led to the proposal of a two-hit hypothesis model by many experts. ^, The first hit is related to exposure of PD components, such as the catheter; hyperosmotic dialysate solutions, which result in mesothelial cell damage; and subsequent peritoneal sclerosis. The second hit is suspected to be related to PD-independent factors such as genetic predispositions and exposure to certain medications. Despite the emergence of a two-hit hypothesis, the broad risk factors associated with EPS highlight the uncertainty and challenges in identifying clear causative factors. Time on PD is the leading risk factor for EPS with the incidence between 0.7 and 13.6 per 1000 patient-years with patients more than 5 years on PD in some reports. The mortality rate among patients diagnosed with EPS is alarmingly high, ranging from 26% to 56% in the first year of diagnosis and higher mortality rates are seen with longer PD vintage. Nonetheless, recent figures indicate better survival rates, likely due to earlier identification and treatment of EPS.

Despite the lack of universally accepted approaches to EPS treatment, management focuses on a combination of supportive, surgical, and pharmacotherapeutic options that should be individualized to meet patient needs. ^{, ,} Patients typically require nutritional support, and, in some instances, total parenteral nutrition is essential. In terms of surgical interventions, patients can undergo a procedure to release bowel adhesions. This requires highly specialized surgical skills to prevent complications such as bowel perforation. Medical treatments can be either supportive or aimed at mitigating the inflammation and scarring seen in EPS. Tamoxifen, an antifibrotic drug, is seen as a potential therapeutic option for EPS. Observational data have shown some benefit with sirolimus and glucocorticoids in the management of EPS as well. ^, Presently, prevention remains elusive due to limited understanding of EPS’s origins. However, early detection and intervention could prove critical in managing this condition effectively. Ultimately, in managing long-term dialysis (>5 years on PD), providers should assess the risks of EPS against HD-associated risks including infection of the vascular access and vascular access-related complications, along with additional dietary and other restrictions affecting lifestyle. For younger patients on PD for extended periods, providers should discuss the possibility of transitioning to home HD or pursuing transplantation. For older patients, the decision to switch modalities must consider the impact on quality of life versus the likelihood of competing mortality risk from comorbid conditions. In cases where patients have a prolonged PD duration with an increased EPS risk and low mortality risk, providers may consider HD after an informed discussion with the patient. It is also to recognize that EPS most commonly presents in cases of PD withdrawal after many years on treatment.

An exit site and tunnel infections are PD-catheter–related infections that can lead to peritonitis, hospitalization, HD transfer, and death. Prompt recognition and treatment are important to reduce risk of complications for patients on PD. An exit site infection is defined by the presence of purulent drainage, which may or may not be accompanied by erythema at the catheter-epidermal interface. A tunnel infection is defined by inflammation, which may include erythema, swelling, tenderness, or induration with or without ultrasonographic evidence of fluid collection along the tunnel site of the catheter. The 2023 updates to ISPD guidelines on catheter-related infections represent a significant shift in the management of exit site and tunnel infections. These revisions redefine the criteria for these infections, setting a goal to keep exit site infection rates below 0.40 episodes per year at risk. ^, The guidelines have also modified recommendations for the use of topical antibiotic creams or ointments at the catheter exit site, now emphasizing the importance of exit site dressing cover and updated antibiotic treatment durations, with a focus on early clinical monitoring. Diagnosing exit site infections relies primarily on clinical assessment, especially noting changes from a patient’s normal healthy exit site.

In terms of treatment, the ISPD guidelines recommend a tailored approach based on the type of infecting organism. For uncomplicated infections, a general recommendation is a 7- to 10-day antibiotic course, extending as needed for more complex conditions like tunnel infections or infections caused by virulent organisms. For infections caused by gram-positive bacteria such as Staphylococcus aureus, including methicillin-resistant S. aureus, antibiotics like vancomycin or linezolid are recommended. For gram-negative bacterial infections including those caused by Pseudomonas species, treatment typically involves antipseudomonal (extended spectrum) penicillins or cephalosporins, potentially combined with aminoglycosides or quinolones. Fungal infections require antifungal agents, such as fluconazole or amphotericin B, depending on the specific fungus.

Peritonitis remains one of the most significant complications of PD and is associated with patient morbidity, mortality, and cost to the health care system (see Table 63.1 for definitions of peritonitis). ^, Given the evolving nature of practice in PD along with microbiological resistance patterns, there have been eight iterations of ISPD recommendations on the prevention and treatment of peritonitis over the past 4 decades with the most recent being published in 2022. In 2022, the ISPD refined definitions for various types of peritonitis and their associated complications. These include refractory, relapsing, and peritonitis leading to catheter removal, HD transfer, hospitalization, and death. Additionally, new categories for cause-specific peritonitis were introduced including pre-PD, enteric, and catheter-related peritonitis. Despite these changes in guidelines, the overarching definition of peritonitis has remained unchanged. The diagnosis of peritonitis is made when at least two of the following criteria have been met: 1. clinical features such as abdominal pain and/or cloudy effluent; 2. dialysis effluent white cell count >100/μL or >0.1 × 10 ⁹ /L (after a dwell time of at least 2 hours), with >50% polymorphonuclear leukocytes; and 3. positive dialysis effluent culture. A reliable diagnosis of peritonitis is based on efficient cultures of the peritoneal fluid. When done correctly, ideally more than 80% should be able to culture a microorganism. The preferred method involves placing 5 to 10 mL of this fluid directly into blood culture containers. ^,

The earliest clinical manifestation often presents as a turbid peritoneal effluent, though some patients may present with abdominal pain before changes in effluent appearance. Although cloudy effluent is a hallmark of peritonitis, differential diagnoses are broad. Potential causes of cloudy effluent include fibrin, chylous ascites, malignancy, eosinophilic peritonitis, and instances of dry peritoneum sampling. It is worth noting that eosinophilic peritonitis is characterized by an absolute number of eosinophils >40 cells, corresponding to more than 10% of total white blood cells in a turbid effluent. The cause of eosinophilic peritonitis is thought to be connected to allergic reactions to specific components of the PD system, leading to hypersensitive responses. It often manifests shortly after the insertion of the PD catheter or subsequent alterations to the PD setup. Possible triggers range from the PD catheter itself, certain medications, the dialysate solution, or occasionally, mycotic infections. ^,

Bacteria can enter the peritoneal cavity by two primary methods, through the catheter (intraluminal route) and along the catheter (pericatheter route). Additionally, there is now an increased awareness of bacteria moving across the bowel mucosa or other tissue layers (transmural route). This is often linked to gastrointestinal conditions such as abscesses, diverticulitis, or constipation, but more often enteric organisms may enter the peritoneum via transmural bowel migration even in the absence of overt bowel compromise. Furthermore, the nasal passages and skin being colonized by S. aureus are known to be associated with infections where the catheter exits the body and other catheter-linked issues, both significant contributors to peritonitis. Additional risk factors for peritonitis encompass touch contamination, bacterial or yeast infections originating from transvaginal routes and systemic bacteremia. ^{, ,}