Noninfectious complications of peritoneal dialysis.

Abstract: Peritoneal dialysis is an established form of renal replacement therapy. With its increasing popularity, we are now encountering a variety of complications. Noninfectious complications are usually less common as compared with infectious complications. In this review, we discuss some of the common noninfectious complications of peritoneal dialysis such as hernias, hydrothorax, hemoperitoneum, pancreatitis, ischemic colitis and necrotizing enterocolitis, pneumoperitoneum, GERD, subcapsular steatosis and hypokalemia. The awareness of these complications will help in early diagnosis and treatment.

Key Words: peritoneal dialysis, noninfectious complications, continuous ambulatory peritoneal dialysis, hernia, hydrothorax, ischemic colitis, pancreatitis, hemoperitoneum, hypokalemia, pneumoperitoneum, gastroesophageal reflux disease, subcapsular steatosis

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Peritoneal dialysis (PD) is a form of renal replacement therapy used by about 140,000 patients worldwide. In the early 1950s and 60s, peritoneal dialysis was predominantly used to manage acute renal failure. Patients with end-stage renal disease (ESRD) were most commonly treated with hemodialysis and intermittent PD was used rarely. The concept of continuous ambulatory peritoneal dialysis (CAPD) was first introduced by Popovich, a biomedical engineer at the University of Texas. In 1978, after a cooperative study done by Moncrief, Nolph, and Popovich, the technique was named as continuous ambulatory peritoneal dialysis. (1) Since its introduction, CAPD has gained tremendous popularity as a form of renal replacement therapy and we therefore are beginning to encounter a variety of complications. Some of the noninfectious complications of peritoneal dialysis are reviewed.

Hernias

Patients on CAPD are prone to develop hernias, particularly those with risk factors. Instillation of dialysis fluid into the peritoneal cavity increases intra-abdominal pressure. According to Laplace law, tension increases on the abdominal wall with increased IP pressure and abdominal radius. The supine position generates the lowest intra-abdominal pressure for a given volume of IP fluid. The intra-abdominal pressure with an empty peritoneal cavity is 0.5 to 2.2 cm [H.sub.2]O, which increases with rising amounts of IP fluid instillation and change in posture. Coughing and straining in the sitting or upright position can give rise to the highest intra-abdominal pressures. (2)

Incidence

The incidence of hernias in CAPD patients is less than 5%. In the early 1980s, the incidence was as high as 10 to 15% per year but with the utilization of paramedian incision and more careful risk factor screening, the incidence has been reduced to less than 5%. (3)

Risk Factors

Multiparous females, elderly males, patients with a history of more than three laparotomies, and those with previous hernia repair have been found to be at increased risk of hernia formation. (4,5) Patients with midline incision for peritoneal dialysis catheter placement are also at increased risk because of anatomic weakness at the linea alba. (3) One study showed that patients with a history of autosomal dominant polycystic kidney disease have a higher incidence of developing hernias because of a higher incidence of patent processus vaginalis. They also have increased intra-abdominal pressure due to large kidneys and weakness of the abdominal wall secondary to underlying defect in extracellular matrix formation. (6) Patients on steroid therapy and those with wound infection are also at high risk. (4)

Types of Hernias

Several different types of hernias have been described in CAPD patients. Some studies found that incisional hernia is the most common form (4,5) while other studies report inguinal or umbilical hernias as the most frequent. (7,8) Other less frequently seen hernias include epigastric, ventral, obturator and hernias through the foramen of Morgagni. (9,10)

Clinical Features

The most common presentation of the hernia is a painless swelling at different sites. (4) Hernias can also present as a tender lump, recurrent Gram negative peritonitis, bowel obstruction and perforation if there is strangulation or incarceration of the bowel. (11,12) An umbilical hernia has a special predilection for strangulation. Bowel incarceration can occur through any kind of hernia, especially the smaller ones. The presence of genital edema may suggest occult indirect inguinal hernias. Obturator hernias may present with paresthesia and hyperesthesia of the anteromedial aspect of the thigh. Hernias through the foramen of Morgagni may present with right-sided chest pain or right hypochondrial pain. (9,10)

Diagnosis: CT peritoneography (CTP) is the most commonly used diagnostic modality in the US and is superior to CT without IP contrast. (13,14) Usually 50 mL of iodinated contrast is mixed with a liter of dialysis solution. To increase the sensitivity, a larger volume should be used, as tolerated. Maneuvers to raise intra-abdominal pressure, for example, moving the patient upright after instillation of fluid may facilitate movement of dye into the tissues. MR peritoneography has similar sensitivity as CTP but is more expensive. Peritoneal scintigraphy is usually used in patients who are allergic to contrast dye and in centers where MR peritoneography is not available. (15)

Treatment: Most of the hernias need surgical repair. Postoperatively, patients should be maintained on low volume intermittent dialysis for a few weeks before CAPD resumes. If the hernia recurs, patients may switch to night time cycler or low volume, more frequent exchanges.

Hydrothorax

Accumulation of fluid in the pleural cavity is called hydrothorax. Increased intra-abdominal pressure after instillation of fluid into the peritoneal cavity can result in leakage of the peritoneal dialysis solution from the peritoneal cavity into the pleural space across the diaphragm. The incidence of hydrothorax varies from 1.6 to 10%. It is unclear why hydrothorax is more commonly seen in females. Stretching of the diaphragm from previous pregnancies could play a role. The pleural to peritoneal connection is almost always on the right side. (16) The presence of heart and pericardium may prevent the leak of fluid across the left hemidiaphragm. (17) Patients with a history of end-stage renal failure secondary to ADPKD (autosomal dominant polycystic kidney disease) undergoing peritoneal dialysis may have a higher risk of hydrothorax. This is most probably secondary to higher than average intra-abdominal pressures because of large kidneys and an inherent defect in the diaphragm due to defective extracellular matrix formation. (18)

Pathogenesis

The pathogenesis of hydrothorax remains unclear. A defect must be present in the diaphragm to leak fluid from the peritoneum into the pleural cavity. A patient who has hydrothorax with the first peritoneal dialysis exchange could have either of the two possibilities. There may be a one-way valve defect or a congenital defect in the tendinous part of the central tendon of the diaphragm. Some authors believe that this one-way valve could be secondary to a defect in the diaphragm or to a hepatic capsule causing tamponade of the backflow of fluid from the pleural to the peritoneal space. (19) Autopsy studies suggest that there is a localized absence of muscle fibers in the tendinous part of the central tendon of the right diaphragm. (16) These missing muscle fibers are replaced with a disordered network of collagens; however, the late appearance of the hydrothorax suggests an acquired defect. For example, in patients with recurrent peritonitis or in patients using large volume exchanges, small discontinuities on the diaphragm due to breakage of collagen fibers may appear. When hydrothorax was investigated by surgery or pleuroscopy, these discontinuities appeared as blisters or blebs on the diaphragmatic pleuroperitoneum. With instillation of fluid into the peritoneal cavity, these blisters swell up, can rupture and thus allow the communication between the peritoneal and pleural cavity. (17) Rarely, dialysate may leak into the pericardial space if communication has been made by previous pericardiocentesis. (20)

Clinical Features

The most common symptom is shortness of breath, which can be mistaken for congestive heart failure. Patients may use more hypertonic dialysis solution to increase ultrafiltration; however, that will lead to a further increase in the intraabdominal pressure and subsequently, increased flux of the dialysate into the pleural space causing worsening of symptoms. Physical examination will reveal decreased or absent breath sounds and stony dullness on percussion.

Diagnosis

Chest x-ray may show right-sided pleural effusion. Thoracentesis can be helpful to confirm the diagnosis. Pleural fluid will have a high glucose concentration and low protein consistent with transudate. Checking D-lactate in the pleural fluid is also helpful, but most laboratories are not equipped to rapidly detect it. (21,22) Therefore, checking glucose in the pleural fluid is the cheaper and easier way to make a quick diagnosis. Instillation of methylene blue into the peritoneal cavity is also helpful to make the diagnosis, but can sometimes lead to chemical peritonitis. (23) Peritoneal scintigraphy, CT peritoneography and MRI peritoneography can also be used.

Treatment

If a patient is acutely short of breath, discontinuation of peritoneal dialysis and immediate thoracentesis will be needed. The patient may benefit from temporary hemodialysis. If pleural effusion is associated with peritonitis, sometimes resting the membrane for a few weeks will allow mesothelium to reconstitute itself over the defect and pleuroperitoneal communication may reseal. If peritonitis is ruled out, more frequent lower volume exchanges can be tried. Obliteration of the pleural space with pleurodesis may be needed in patients who have recurrent pleural effusions. Chemical pleurodesis has been performed with tetracycline, talc and autologous blood. (21,24-26) There is no evidence to suggest that one is superior to the other. The main side effect of these sclerosing agents is pain. Surgical treatment is the last option for recurrent hydrothorax. (27)

Hemoperitoneum

The presence of blood in peritoneal dialysis effluent is called hemoperitoneum. This is a benign complication of chronic peritoneal dialysis. Only a very small amount of bleeding is required to make dialysate appear bloody. Even 1 mL of whole blood injected into 2 L of an effluent bag can make the fluid readily blood tinged, and injection of 7 mL of blood can make the entire volume as red as fruit juice. (28) Hemoperitoneum has a wide differential diagnosis. Blood tinging of dialysate is commonly seen after peritoneal dialysis catheter placement as a result of direct vascular and visceral damage. It rapidly clears with a few in-and-out exchanges. The most common and benign cause of hemoperitoneum in women of reproductive age is menstruation. Two theories are proposed to explain its mechanism. First, endometrial tissue, if present in the peritoneum, will shed simultaneously with uterine endometrium. Secondly, shed endometrial tissue and blood moves out of the cervix through the fallopian tubes in a retrograde fashion. (29) Peritoneal bleeding starts a few days before vaginal menstrual flow. Forty-one percent of the episodes of hemoperitoneum occur just before or with menstruation and 57% occur at midcycle during ovulation with rupture and release of ovum. (30) Other causes of hemoperitoneum in women of reproductive age are ovulation and ruptured ovarian cyst. (31) Trauma, procedure to the abdominal area, bleeding disorders or anticoagulation therapy can also predispose to hemoperitoneum. Bleeding into a hepatic or renal cyst with rupture into the peritoneal cavity can also cause hemoperitoneum. Acute and chronic pancreatitis, patients with sclerosing peritonitis and peritoneal calcification in patients with secondary hyperparathyroidism can all present with hemoperitoneum. (32,33)

Diagnosis

Peritoneal fluid cell count, culture and sensitivity, peritoneal amylase level (>50 [micro]m/L suggests an intra-abdominal process) should be obtained. Peritoneal dialysate hematocrit >2% suggests IP pathology. CT scan of the abdomen and pelvis should be done if ultrasound is negative or inconclusive. In patients who have persistent bleeding, isotope-labeled RBC scan can be done to localize the site of bleeding, which can then be selectively embolized. (34)

Management of Hemoperitoneum

Patients with asymptomatic hemoperitoneum can be treated with unwarmed 1.5% dextrose-containing dialysate for 1 to 3 rapid exchanges at home. No dwell time is required, each exchange lasting about 40 minutes. It has been thought that cool dialysate causes vasoconstriction and subsequent hemostasis. (35) Patients should be reminded that they must seek medical attention if they have other symptoms like hypotension, tachycardia, lightheadedness, or severe abdominal pain.

Patients with hemoperitoneum are at a high risk for clotting the PD catheter. IP heparin at a dose of 500 to 1000 U/L should be used as long as dialysate has visible blood or fibrin. Women of reproductive age who have excessive bleeding with their menstrual cycle should be treated with hormonal therapy.

Pancreatitis

In addition to common causes of pancreatitis such as gallstones, alcohol or drugs, peritoneal dialysate and tubing can act as irritants and cause acute pancreatitis which may reoccur when rechallenged with peritoneal dialysate. (36) Diagnosis of pancreatitis in CAPD patients is difficult because the presentation can be similar to peritonitis. It should be considered whenever there is culture-negative peritonitis or if abdominal pain fails to resolve. Whether pancreatitis is more common in CAPD as compared with hemodialysis is controversial. (37) Diagnosis can be established by checking effluent amylase level, which if greater than 100 U/L, suggests pancreatitis. A serum amylase level three times above the normal limit in chronic renal failure patients is suggestive of acute pancreatitis. (38) However, a normal level does not exclude the diagnosis. Most patients are treated conservatively. Few patients may need to undergo surgical exploration. Mortality from pancreatitis is higher when compared with non-ESRD patients. Diagnosis can be delayed because of the assumption that the abdominal symptoms are from peritonitis.

Ischemic Colitis and Necrotizing Enteritis

Ischemic colitis can occur rarely in PD patients. The most likely cause is hypotension and subsequent hypoperfusion of the bowel. (39,40) Severe gastrointestinal bleeding from dilated submucosal vessels has been seen in CAPD patients using hypertonic dextrose solutions. The bleeding stopped when the patient switched to hemodialysis. (41)

Pneumoperitoneum

It is not unusual to see free air under the diaphragm in peritoneal dialysis patients. Air can be infused with the dialysis fluid especially with flush before fill technique. In asymptomatic CAPD patients, this condition is benign and the air should gradually reabsorb. However, if the patient presents with abdominal pain, perforation of viscus should be ruled out. (42)

Gastroesophageal Reflux Disease

Upper gastrointestinal symptoms are frequently observed in CAPD patients. Eighteen percent of patients present with nausea and a sensation of fullness and 14% present with vomiting. (43) CAPD patients with persistent nausea and vomiting should be evaluated with esophageal manometry and 24 hours pH monitoring to establish a diagnosis of GERD. (44)

Treatment: In addition to treatment with proton pump inhibitors, low volume dialysis can be tried. If adequate clearance cannot be achieved, the patient should be switched to hemodialysis.

Subcapsular Steatosis

This is a unique hepatic lesion seen in CAPD patients receiving IP insulin. A layer of fat is deposited under the hepatic capsule exposed to the peritoneal cavity. Thickness of fatty tissue correlates with the degree of obesity as well as the dose of IP insulin. Pathologically, there may be steatonecrosis but the liver function remains normal. When evaluated by CT scan, the abnormality is seen primarily under the liver capsule in CAPD-induced steatonecrosis whereas in obesity, it is seen throughout the liver. Nonalcoholic steatonecrosis is also seen in Type 2 diabetes and after jejunoileal bypass. (45,46)

Hypokalemia

Hypokalemia is the most common electrolyte abnormality seen in PD patients. It results from ongoing loss in the dialysate and the absence of potassium in the PD solutions. It can be treated with oral supplements and a potassium-liberal diet. In rare cases, potassium may need to be added to PD fluid. In asymptomatic patients, the level can be maintained above 3 mmol/L. In patients taking digoxin or with a history of cardiac arrhythmias, the potassium level should be maintained above 3.5 mmol/L. (47)

References

1. Popovich RP, Moncrief JW, Nolph KD, et al. Continuous ambulatory peritoneal dialysis. Ann Intern Med 1978;88:449-456.

2. Twardowski ZJ, Khanna R, Nolph KD, et al. Intraabdominal pressures during natural activities in patients treated with continuous ambulatory peritoneal dialysis. Nephron 1986;44:129-135.

3. Spence PA, Mathews RE, Khanna R, et al. Improved results with a paramedian technique for the insertion of peritoneal dialysis catheters. Surg Gynecol Obstet 1985;161:585-587.

4. Digenis GE, Khanna R, Mathews R, et al. Abdominal hernias in patients undergoing continuous ambulatory peritoneal dialysis. Perit Dial Int 1982;2:115-117.

5. O'Connor J, Rigby R, Hardie I. Abdominal hernias complicating continuous ambulatory peritoneal dialysis. Am J Nephrol 1986;6:271-274.

6. Morris-Stiff G, Coles G, Moore R, et al. Abdominal wall hernia in autosomal dominant polycystic kidney disease. Br J Surg 1997;84:615-617.

7. Rocco M, Stone W. Abdominal Hernias in chronic peritoneal dialysis patients: A review. Perit Dial Int 1985;5:171-174.

8. Wise M, Manos J, Gokal R. Small umbilical hernias in patient on CAPD (letter). Perit Dial Int 1984;4:270-271.

9. Grossi C, Faiolo S, Tettamanzi F, et al. Obturator hernia a rare complication in a CAPD patient: a report of a case. Perit Dial Int 1993;13:S11.

10. Ramos J, Burke D, Veitch P. Hernia of Morgagni in patients on continuous ambulatory peritoneal dialysis. Lancet 1982;1:161-162.

11. Griffin PJ, Coles GA. Strangulated hernias through Tenckhoff cannula sites. Br Med J (Clin Res Ed) 1982;284:1837.

12. Power DA, Edward N, Catto GR, et al. Richter's hernia: an unrecognised complication of chronic ambulatory peritoneal dialysis. Br Med J (Clin Res Ed) 1981;283:528.

13. Twardowski ZJ, Tully RJ, Ersoy FF, et al. Computerized tomography with and without intraperitoneal contrast for determination of intraabdominal fluid distribution and diagnosis of complications in peritoneal dialysis patients. ASAIO Trans 1990;36:95-103.

14. Hollett MD, Marn CS, Ellis JH, et al. Complications of continuous ambulatory peritoneal dialysis: evaluation with CT peritoneography. AJR Am J Roentgenol 1992;159:983-989.

15. Juergensen PH, Rizvi H, Caride VJ, et al. Value of scintigraphy in chronic peritoneal dialysis patients. Kidney Int 1999;55:1111-1119.

16. Grefberg N, Danielson BG, Benson L, Pitkanen P. Right-sided hydro-thorax complicating peritoneal dialysis. Report of 2 cases. Nephron 1983;34:130-134.

17. Boeschoten EW, Krediet RT, Roos CM, et al. Leakage of dialysate across the diaphragm: an important complication of continuous ambulatory peritoneal dialysis. Neth J Med 1986;29:242-246.

18. Fletcher S, Turney JH, Brownjohn AM. Increased incidence of hydro-thorax complicating peritoneal dialysis in patients with adult polycystic kidney disease. Nephrol Dial Transplant 1994;9:832-833.

19. Garcia Ramon R, Carrasco AM. Hydrothorax in peritoneal dialysis. Perit Dial Int 1998;18:5-10.

20. Hou CH, Tsai TJ, Hsu KL. Peritoneopericardial communication after pericardiocentesis in a patient on continuous ambulatory peritoneal dialysis with dialysis pericarditis. Nephron 1994;68:125-127.

21. Benz RL, Schleifer CR. Hydrothorax in continuous ambulatory peritoneal dialysis: successful treatment with intrapleural tetracycline and a review of the literature. Am J Kidney Dis 1985;5:136-140.

22. Schleifer CR, Teehan BP, Reichard GA, et al. Acid-base balance in continuous ambulatory peritoneal dialysis. Proc Clin Dial Transplant Forum 1980;10:100-104.

23. Macia M, Gallego E, Garcia-Cobaleda I, et al. Methylene blue as a cause of chemical peritonitis in a patient on peritoneal dialysis. Clin Nephrol 1995;43:136-137.

24. Tang S, Chui WH, Tang AW, et al. Video-assisted thoracoscopic talc pleurodesis is effective for maintenance of peritoneal dialysis in acute hydrothorax complicating peritoneal dialysis. Nephrol Dial Transplant 2003;18:804-808.

25. Catizone L, Zuchelli A, Zucchelli P. Hydrothorax in a PD patient: successful treatment with intrapleural autologous blood instillation. Adv Perit Dial 1991;7:86-90.

26. Mak SK, Chan MW, Tai YP, et al. Thoracoscopic pleurodesis for massive hydrothorax complicating CAPD. Perit Dial Int 1996;16:421-423.

27. Allen SM, Matthews HR. Surgical treatment of massive hydrothorax complicating continuous ambulatory peritoneal dialysis. Clin Nephrol 1991;36:299-301.

28. Nace G, George A Jr, Stone W. Hemoperitoneum: A red flag in CAPD. Perit Dial Int 1985;5:42-44.

29. Blumenkrantz M, Gallagher N, Bashore R. Retrograde menstruation in women undergoing chronic peritoneal dialysis. Obstet Gynecol 1981;57:667-670.

30. Harnett JD, Gill D, Corbett L, et al. Recurrent hemoperitoneum in women receiving continuous ambulatory peritoneal dialysis. Ann Intern Med 1987;107:341-343.

31. Fraley DS, Johnston JR, Bruns FJ, et al. Rupture of ovarian cyst: massive hemoperitoneum in continuous ambulatory peritoneal dialysis patients: diagnosis and treatment. Am J Kidney Dis 1988;12:69-71.

32. Francis DM, Busmanis I, Becker G. Peritoneal calcification in a peritoneal dialysis patient: a case report. Perit Dial Int 1990;10:237-240.

33. Greenberg A, Bernardini J, Piraino BM, et al. Hemoperitoneum complicating chronic peritoneal dialysis: single-center experience and literature review. Am J Kidney Dis 1992;19:252-256.

34. Twardowski ZJ, Schreiber MJ Jr, Burkart JM. A 55-year-old man with hematuria and blood-tinged dialysate. Perit Dial Int 1992;12:61-71.

35. Goodkin DA, Benning MG. An outpatient maneuver to treat bloody effluent during continuous ambulatory peritoneal dialysis (CAPD). Perit Dial Int 1990;10:227-229.

36. Flynn C, Chandran P, Shadur C. recurrent pancreatitis in a patient on CAPD (letter). Perit Dial Int 1986;6:106.

37. Gupta A, Yuan ZY, Balaskas Ev, et al. CAPD and pancreatitis: no connection. Perit Dial Int 1992;12:309-316.

38. Royse VL, Jensen DM, Corwin HL. Pancreatic enzymes in chronic renal failure. Arch Intern Med 1987;147:537-539.

39. Steiner RW, Halasz NA. Abdominal catastrophes and other unusual events in continuous ambulatory peritoneal dialysis patients. Am J Kidney Dis 1990;15:1-7.

40. Wehling M, Jenni R, Steurer J, et al. Ischaemic colitis in patient undergoing continuous ambulatory peritoneal dialysis. Perit Dial Int 1982;2:123-124.

41. Tomson C, Morgan A. Bleeding from small intestinal telangiectasis complicating CAPD (letter). Perit Dial Int 1985;5:258.

42. Kiefer T, Schenk U, Weber J, et al. Incidence and significance of pneumoperitoneum in continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1993;22:30-35.

43. Bjorvell H, Hylander B. Functional status and personality in patients on chronic dialysis. J Intern Med 1989;226:319-324.

44. Kim MJ, Kwon KH, Lee SW. Gastroesophageal reflux disease in CAPD patients. Adv Perit Dial 1998;14:98-101.

45. Wanless IR, Bargman JM, Oreopoulos DG, et al. Subcapsular steatone-crosis in response to peritoneal insulin delivery: a clue to the pathogenesis of steatonecrosis in obesity. Mod Pathol 1989;2:69-74.

46. Burrows CJ, Jones AW. Hepatic subcapsular steatosis in a patient with insulin dependent diabetes receiving dialysis. J Clin Pathol 1994;47:274-275.

47. Bargman J, Jamison R. Disorders of potassium homeostasis. In: Sutton R, Dirks J, eds. Diuretics: Physiology, Pharmacology and Clinical Use. Philadelphia, W.B. Saunders, 1986, pp 296-319.

Humor is just another defense against the universe.
--Mel Brooks

Tapasi C. Saha, MD, and Harmeet Singh, MD

From the Section of Nephrology, Brody School of Medicine, East Carolina University, Greenville, NC.

Reprint requests to Tapasi C. Saha, MD, Assistant Clinical Professor, Section of Nephrology, Brody School of Medicine, East Carolina University, 2355 West Arlington Boulevard, Greenville, NC 27834. Email: [e-mail]

Accepted June 29, 2006.

RELATED ARTICLE: Key Points

* Since noninfectious complications are much less common than infectious complications, diagnosis might be delayed due to lack of awareness.

* Hernias can present as a painless swelling or a tender lump.

* Hydrothorax commonly presents on the right side.

* Hemoperitoneum is a common benign finding in menstruating females.

* Hypokalemia is the most common electrolyte abnormality seen in peritoneal dialysis patients.