Gastrointestinal complications of renal transplantation

Gastrointestinal Complications of Renal Transplantation William

M. Thompson,

William

Meyers,

complications ocASTROINTESTINAL cur with distressing frequency in patients who have undergone renal transplantation. Virtually every segment of the gastrointestinal tract can be a site of complication. The more serious of these complications, such as bowel perforation, bowel necrosis, and hemorrhage, are common causes of death in patients who have undergone successful renal transplantation ~3,12,13.16.17,21),25.29,3~~

G

The immunosuppressive therapy that is necessary in the transplantation regimen can be a major contributing factor to many of these complications. Steroids can mask the clinical presentation of some complications and thereby delay accurate diagnosis. The dangers inherent in the common complications that occur in patients who have undergone renal transplantation justify a vigorous diagnostic approach that may include plain films, various contrast examinations, ultrasound, angiography, or whatever other modality seems appropriate in a given clinical setting. This article will review the experience of others collected from the medical literature and will present an overview of our own experience with gastrointestinal complications that have been encountered in patients who have undergone renal transplantation at the Duke University Medical Center and the Durham Veterans Administration Hospital between February, 1965 and February, 1978. A detailed statistical review of all of the gastrointestinal complications in our series is in progress and will be published in the near future.

William M. Thompson, M.D.: Associate Professor oj Radiology, Duke University Medical Center, Durham, N.C. Picker Scholar, James Picker Foundation. William Meyers, M.D.: Surgical Resident, Department of Surgery, Duke University Medical Center, Durham, N.C. Hilliard F. Seigler, M.D.: Professor oJ Surgery, Duke University Medical Center, Durham, N.C. Reed P. Rice, M.D.: Professor of Radiology, Duke University Medical Center. Durham, N.C. Reprint requests should be addressed to Dr. William M. Thompson, Department of Radiology, Duke University Medical Center, Durham, N.C. 27710.
Seminars in Roentgenology, Vol. XIII. No 4 (October). 1978

Hilliard

F. Seigler.

and Reed P. Rice

We have had 343 patients who have received 368 kidney allographs, 194 of which came from living related donors. Since 1965, azathioprine and prednisone have been used as immunosuppressive agents, and since 1968 many cadaver kidney recipients have received in addition antilymphocyte globulin on a randomized basis. Rejection episodes have been treated by highdosage steroids and irradiation. Many serious complications have occurred soon after transplantation and during episodes of rejection. A number of fatal complications also have occurred many months after successful renal transplantation. ESOPHAGITIS

Peptic Esophagitis

Posttransplantation reflux esophagitis has been encountered both with and without a pretransplantation history of peptic esophagitis. Esophagitis usually does not constitute a fatal complication, but the symptoms may be incapacitating.Z5,‘Y A barium esophagogram may demonstrate very little evidence of esophagitis unless the involvement has progressed to the point of stricture formation or there is grossly demonstrable gastroesophageal reflux (Fig. 1). Esophagoscopy is a much more reliable way of documenting peptic esophagitis. Monilial

Esophagitis

Monilial esophagitis is a common complication of many debilitating diseases, and patients with renal failure before and after renal transplantation are no exception.‘x Generally patients with monilial esophagitis will experience painful swallowing, with fairly rapid progression of symptoms. Clinical inspection of the pharynx and esophagoscopy usually will reveal the characteristic mucosal changes. Radiographic evaluation of the esophagus usually is diagnostic. Typically there is gross irregularity of the mucosal fold pattern of the esophagus, with loss of normal peristaltic activity. Occasionally areas of mucosal irregularity may be localized (Fig. 2). The esophagus may be either slightly dilated or narrowed. The 319

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Fig. 1. esophagus.

THOMPSON

Peptic

esophagus

in a 33-year-old

man

3 weeks

posttransplantation.

Arrows

mark

ulcerations

ET AL

in the distal

Fig. 2. Monilial esophagitls in a 23-year-old man who had recently undergone cadaver renal transplantation. (A) Routine esophagogram shows minimal irregularity in the midesophagus (arrow). (6) Double contrast study shows the area to better advantage (arrows). There is diffuse irregularity of the esophageal mucosa that was not apparent in (A).

GASTROINTESTINAL

COMPLICATIONS

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use of high-density barium and a double contrast technique makes it possible to demonstrate even subtle and patchy areas of monilial esophagitis (Fig. 2B). It is important to repeat the esophagogram until the esophagus has returned to normal, regardless of good clinical response. Severe strictures of the esophagus from monilial esophagitis may develop even though the symptoms resolve rapidly after initiation of therapy.” GASTRODUODENAL

ULCERATION

Ulcer disease is a common problem that frequently is serious and may even be fatal in patients who have undergone renal transplantation.‘.“,‘2.24.35 Exsanguinating gastrointestinal

Fig. woman

3. Active antral ulcer (arrows) 3 weeks after renal transplantation.

in a 30-year-old

321

hemorrhage and perforated ulcer are the most common serious complications, and they are significant causes of death in patients who have undergone renal transplantation. The problem of perforated ulcer frequently is compounded by delay in diagnosis. Symptoms often are masked by the steroid therapy that is part of the posttransplantation regimen. Awareness that subtle clinical signs may accompany ulcer perforation justifies careful evaluation of routine radiographs and aggressive use of studies employing water-soluble contrast medium. There is disagreement in the literature concerning the cause of recurrent ulcer disease or development of new ulcers in patients following

322

THOMPSON

renal transplantation. There also is disagreement concerning the value of routine screening of patients for peptic ulcer disease prior to renal transplantation. The effects of renal transplantation and the drugs used for immunosuppression on the course of ulcer disease are not known.7.“,21 A high incidence of gastric ulcer as compared with duodenal ulcer has been reported in renal transplantation patients.“.‘“,‘“,‘!’ Our own experience reflects this increase in the number of gastric ulcers relative to duodenal ulcers. Other than distribution, there is nothing distinctive about the radiographic pattern of ulcer disease in patients who have undergone renal transplantation (Fig. 3). Many of the ulcers are superficial, and endoscopy is more accurate than routine upper GI series for their diagnosis.“” When perforation is suspected, careful selection of the appropriate study with watersoluble contrast medium must be made. In our series, we have had 12 patients with lower intestinal perforation, compared with 6 patients with perforation of the stomach or duodenum. Therefore we usually perform an enema with water-soluble contrast medium before an upper GI series. We reverse this routine in the patient with a previous history of peptic ulcer disease. MASSIVE

GASTROINTESTINAL HEMORRHAGE

Peptic ulcer disease is the most common cause of massive and frequently fatal gastrointestinal hemorrhage in patients following renal transplantation.“‘~‘“~“” However, gastritis as well as superficial ulcerations in the small and large bowel, particularly the cecum, are other sources of major hemorrhage that have been demonstrated.“6 A vigorous diagnostic approach is warranted in any patient with lifethreatening gastrointestinal hemorrhage, and renal transplantation patients are no exception. When the clinical evidence suggests an upper gastrointestinal bleeding site, gastroduodenoscopy usually is the diagnostic modality that offers the best chance for accurate diagnosis. Emergency angiography also is highly accurate, and it offers the added potential for therapy with either vasopressive agents or catheter embolization. A barium upper GI series is not as accurate as endoscopy and

ET AL

angiography in the emergency work-up of patients with gastrointestinal hemorrhage.“:’ When the nasogastric aspirate is negative for blood and there is clinical evidence to suggest a small bowel or colon bleeding site, angiography is unquestionably the procedure of first choice for evaluation of the severely bleeding patient.23.3Ci Colonoscopy and emergency barium enema examination are not likely to be helpful; furthermore, barium will interfere with a subsequent arteriogram. As with bleeding lesions of the upper gastrointestinal tract, arteriography offers both diagnostic and therapeutic potential. Approximately two-thirds of lower intestinal bleeding lesions can be diagnosed accurately with arteriographic techniques, and in up to 90% of the demonstrable lesions bleeding can be controlled effectively with catheter techniques.‘:‘,:j” BOWEL

PERFORATION

Bowel perforation is a relatively common and frequently fatal complication in patients who have undergone renal transplantation. Our own experience, coupled with that in the literature, documents the fact that there is an unusually high incidence of ileal and colon perforation in renal transplantation patients.‘~‘~X~“‘,“~“i. ‘L1,4L’.~,i.:ll,..~l.:i; Many colon perforations have been associated with diverticular disease. In patients on steroid therapy, the increased incidence of diverticulitis may be caused by atrophy of the intestinal lymphoid collections and resultant decreased resistance to bacterial invasion.“.“’ It is also probable that when diverticulitis does occur there is less likely to be a walled-off perforation, so that generalized peritonitis frequently supervenes. Ileocolonic perforations also have been associated with fecal impaction related to nonabsorbable antacids, sodium polystyrene sulfonate (Kayexalate) enemas, incorrect trochar placement for dialysis, ischemia, and infectious coliti~~2,1.~.!‘.1~1.II.I~i.~l.~~.Y6.~X,~l~~.~~~.~~i Whatever the reason for the perforation, the symptoms frequently are masked by the maintenance steroid therapy. It is important that there be an aggressive approach to diagnosis, since mortality increases with delay. In our own series of 12 patients, the interval from onset of symptoms to diagnosis ranged from 1 to 13 days, with a mean of 4 days. In our series,

GASTROINTESTINAL

Fig. right perforz of the month’

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323

4. Extraluminal gas (arrows) in the upper abdomen secondary to a lted sigmoid diverticulum. Supine film abdomen in a 45year-old man 9 s after renal transplantation.

Fig. 5. Perforated colon diverticulum 3 years after cadaver renal transplantation. (Al Supine film of the abdomen shows an abnormal collection of gas (arrow). (B) Enema with water-soluble contrast medium demonstrates extravasation (arrows) from a diverticulum in the left colon. Colostomy was performed, and the patient is alive 3 years later. (Reproduced by permission from Thompson et al: Am J Roentgen01 125:723-730.1975.)

324

THOMPSON

ET AL

Fig. 6. Rectal perforation in a 33-year-old man who had received his second cadaveric renal transplant 4 days earlier. Kayexalate enemas were being given for hyperkalemia. (A) The free air under the right hemidiaphragm was not present on a film the day before. (9) Enema with water-soluble contrast medium demonstrates extravasation into the peritoneal cavity. At operation, a 3-cm area of necrosis was demonstrated in the anterior rectal wall. Sigmoid colostomy and oversewing of the perforation were performed. but the patient died on the 27th postoperative day. (Reproduced by permission from Thompson et al. Am J Roentgen01 125:723-730.1976.)

80% of patients died as a result of bowel perforation. In most of these patients the diagnosis was suggested by the radiologic findings prior to significant clinical evidence of perforation and peritonitis.“7 Critical evaluation of the plain film, including upright and decubitus views, in search of free peritoneal gas or extraluminal gas associated with an abscess is essential (Figs. 4--8). We encourage the prompt use of an enema with watersoluble contrast medium when there is undiagnosed abdominal pain in a patient who has undergone renal transplantation. The bowel perforation may occur soon after the operation or months or years after successful renal transplantation.

As was mentioned previously, we have had significantly more perforations of the ileum and colon than perforations of the stomach and duodenum.“7 Hadjiyannakis et al.‘:’ have reported a similar experience. Thus, when confronted with plain abdominal film evidence of extraluminal gas in the posttransplantation patient, we usually perform an enema with water-soluble contrast medium as the first procedure. However, if there is a strong history of ulcer disease, we sometimes perform the upper GI series first (Fig. 8). FECAL

IMPACTION

Several case reports in the literature have documented gross fecal impaction resulting

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OF RENAL

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Fig. 7. Fecal antacid colon impaction. (Al Supine film of the abdomen in a 43-year-old man 7 days after renal transplantation shows a large amount of feces and radiopaque material retained in the colon. No free air was demonstrated on the upright film. (B) Upright film obtained during an upper GI series 6 hr later shows a large amount of free air. At laparotomy, a fecal impaction was found in the right colon, with perforation secondary to pressure necrosis. The patient died 14 days later. (Reproduced by permission from Thompson et al: Am J Roentgen01 125:723-730.1975.)

from the use of nonabsorbable antacids in patients who have undergone renal transplantation (Fig. 7).2.5*2’*37In some cases, the fecal impaction has resulted in bowel necrosis. The impactions frequently occur in the right colon or small bowel. Most authors now recommend

avoiding the use of nonabsorbable antacid gels, such as aluminum hydroxide, in these patients.” OBSTRUCTION

AND

ILEUS

Postoperative ileus is, of course, common in patients who have undergone renal transplanta-

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THOMPSON

ET AL

Fig. 8. Perforated duodenal ulcer in a 35-year-old man 8 months following renal transplantation. (A) Extraluminal gas is seen over the liver (arrows) on the upright film. (8) Upper GI series with water-soluble contrast medium demonstrates free perforation of a duodenal ulcer (arrows). The patient died following surgical closure of the perforated ulcer.

tion. It may be difficult to differentiate ileus from bowel obstruction in the early postoperative period. As in other postoperative situations, adhesions are the most common cause of mechanical bowel obstruction. As was mentioned in the preceding section, nonabsorbable antacid gels also can cause mechanical obstruction. PANCREATITIS

Pancreatitis has been reported in 2% to 6% of all renal transplantation patients. A 50% mortality

has

been

reported~!~~l5.lfi,~~l~~~,~~i~~~~,:~X

The cause may be related to steroid therapy, but there is also a known association between hyperparathyroidism and pancreatitis, and patients with chronic renal disease often have evidence of secondary hyperparathyroidism. There may be immunologic factors as well; cytomegalovirus has been found in the pancreas of patients with pancreatitis after renal transSome of the patients with plantation.“,‘“,:”

Fig. 9. Pancreatitis. PA film from an upper 01 series showing widening of the duodenal loop with edematous mucosa. Clinical findings of pancreatftis appeared in this 35year-old man a month after renal transplantation.

GASTROINTESTINAL

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OF RENAL

Table 1. Gastrointestinal Complications Transplantation Patients

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TRANSPLANTATION

patients who died developed acute pancreatitis more than 3 months following transplantation. Only 1 of 4 patients who developed pancreatitis secondary to surgical trauma died. The critical importance of suspecting pancreatitis in patients receiving immunosuppressive drugs, either soon after or long after transplantation, cannot be overemphasized. The usual abdominal signs of pancreatitis can be masked by steroid therapy. The best chance for survival of these patients rests in early diagnosis and prompt treatment. The reported radiographic features of pancreatitis in the patient who has undergone renal transplantation are no different from those in the nontransplantation patient (Fig. 9). The findings vary from a sentinel 100~“~to those of a pancreatic abscess or pseudocyst.‘”

in Renal

Esophagitis’0.‘3.‘9.~~,~~.~~ Monilial Peptic Ulcer disease7.10.16.20,24,~~.~~,~~ Stomach Duodenum Bowel perforation Upper: stomach and duodenum’3~‘7~25~27~33 Lower: ,leum and ~~,~~1.4.8.10.13.14.~,.~~.~~.~~.~~.~~ Fecal Impaction2~5~2’ Obstruction Perforation Bowel obstruction and ileus16.27,33 Gastrointestinal bleeding3~9~‘0”3~‘8~~~.~~~~~~~~~~~ Gastritis Cecal ulceration Source unknown Pancreatltis’0.‘5.‘6,~~,~,.~,,~~,~~ Miscellaneous Pneumatosis cystoides intestinalisJ6 lntraabdominal abscess-peritonitis without perforation’6,34 Inflammatory bowel disease-pseudomembranous ColltIs~~~~~~~ CholecystitislG Bowel infarction16

MISCELLANEOUS GASTROINTESTINAL COMPLICATIONS

Hepatitjs3.77.20.33

pancreatitis reported in the literature and in our own series were alcohol abusers. Complications of pancreatitis have included hemorrhage from erosion into a major artery, pseudocyst, and pancreatic abscess. Johnson and Nabseth’” reported a survey of 1321 renal transplants in which 23 cases of pancreatitis were documented. Six of the 12

Various other complications have occurred in renal transplantation patients (Table 1); they include acute cholecystitis, appendicitis, infectious colitis, pneumatosis cystoides intestinabs, bowel infarction, unexplained peritonitis, and intraabdominal abscess. Recently, cytomegalovirus has been reported in association with a number of gastrointestinal complications in renal transplantation patients.“‘,‘” Hepatitis and subclinical alterations in liver function studies also are relatively common in this patient population.“~“~““~:‘”

REFERENCES I. Aaron KE, Dailey TH: Survival after colonic perforation of a patient with a transplanted kidney. Report of a case. Dis Colon Rectum 17:103- 105, 1974 2. Aguilo JJ, Zincke H, Woods JE, et al: Intestinal perforation due to fecal impaction after renal transplantation. J Urol 116:153-155, 1976 3. Aldrete JS, Sterling WA, Hathaway BM, et al: Gastrointestinal and hepatic complications affecting patients with renal allografts. Am J Surg 129:115-124, 1975 4. Bernstein WC, Nivatvongs S, Tallent MD: Colonic and rectal complications of kidney transplantation in man. Dis Colon Rectum 16:255-263, 1973 5. Brettschneider L, Monafo W, Osborne DP: Intestinal obstruction due to antacid gels. Complication of medical therapy for gastrointestinal bleeding. Gastroenterology 49~291-294, 1965 6. Canter JW, Shorb PE Jr: Acute perforation of colonic diverticula associated with prolonged adrenocorticosteroid therapy. Am J Surg 121:46-51, 1971

7. Chisholm GD, Mee AD, Williams G, et al: Peptic ulceration, gastric secretion and renal transplantation. Br Med J 1:1630- 1633, 1977 8. Demling PH, Salvatierra 0 Jr, Belzer FO: Intestinal necrosis and perforation after renal transplantation. Arch Surg 110:251 253, 1975 9. Diethelm AC: Surgical management of complications ofsteroid therapy. Ann Surg 185:251 261, 1977 10. Diethelm AC, Gore I, Ch’ien LT, et al: Gastrointestinal hemorrhage secondary to cytomegalovirus after renal transplantation. A case report and review of the problem. Am J Surg 131:371-374, 1976 I I. Doherty CC, McGeown MG: Peptide ulceration, gastric secretion and renal transplantation (correspondence). Br Med J 2:188, 1977 12. Griffiths HJ: Radiology of Renal Failure. WB Saunders, Philadelphia, 1976, pp 156-177 13. Hadjiyannakis EJ, Smellie WA, Evans DB, et al:

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Gastrointestinal complications Lancet 2:781-785, 1971 14. Hognestad J, Flatmark transplant patients. Stand I976

THOMPSON after

renal

transplantation.

A: Colon perforation in renal J Gastroenterol 11:289-292,

15. Johnson WC, Nabseth DC: Pancreatitis in renal transplantation. Ann Surg 171:309-314, 1970 16. Julien PJ, Goldberg HI, Margulis AR, et al: Gastrointestinal complications following renal transplantation. Radiology 117:37-43, 1975 17. Kuhlback B, Lilius P: Late complications after primarily successful renal transplantation. Acta Med Stand 2002-24, 1976 18. Lewicki AM, Moore JP: Esophageal moniliasis. A review of common and less frequent characteristics. Am J Roentgen01 125:218 -225, 1975 19. Lewicki AM, Saito S, Merrill JP: Gastrointestinal bleeding in the renal transplant patient. Radiology 102:533 -537, 1972 20. Libertino JA, Zinman L, Dowd JB, et al: Gastrointestinal complications related to human renal homotransplantation. Surg Clin North Am 51:733 737, 1971 21. Lipschulz DE, Easterling RE: Spontaneous perforation of the colon in chronic renal failure. Arch Intern Med 132:758 -759, 1973 22. Misra MK, Pinkus GS, Birtch AG. et al: Major coIonic diseases complicating renal transplantation. Surgery 73:9422948, 1973 23. Oddson TA, Johnsrude IS, Jackson DC, et al: The diagnostic evaluation of patients with acute gastrointestinal hemorrhagee with special attention to the changing role of barium examinations. Radio1 Clin North Am 16:1233134, 1978 24. Owens ML, Passaro E Jr, Wilson SE, et al: Treatment of peptic ulcer disease in the renal transplant patient. Ann Surg 186:17 21, 1976 25. Owens ML, Wilson SE, Saltzman R, et al: Gastrointestinal complications after renal transplantation. Predictive factors and morbidity. Arch Surg I I I :467 -47 I, 1976

ET AL.

26. Penn I, Brettschneider L, Simpson K, et al: Major colonic problems in human homotransplant recipients. Arch Surg 100:61 65, 1970 27. Penn I, Groth CG, Brettschneider L, et al: Surgically correctable intra-abdominal complications before and after renal homotransplantation. Ann Surg 168:865 870, 1968 28. Perloff LJ, Chon H, Petrella EJ, et al: Acute colitis in the renal allograft recipient. Ann Surg 183:77 83, 1976 29. Peterson R: Gastrointestinal abnormalities in renal homotransplant patients. J Can Assoc Radio1 27:240-249, 1976 30. Powis SJA, Barnes AD, Dawson-Edwards PD, et al: Ileocolonic problems after cadaveric renal transplantation. Br Med J I:99 101, 1972 31. Renning JA, Warden CD, Stevens LE, et al: Pancreatitis after renal transplantation. Am J Surg 123:293 296, 1912 32. Renshaw TS, Phelps DB: Perforation of colonic diverticula. A life-threatening postoperative complication in patients receiving long-term corticosteroid therapy. J Bone Joint Surg [Am] 54:1070 1072, 1972 33. Rosekrans P: Gastrointestinal complications after renal transplantation. Radiologia Clinica 47:32 43, 1978 34. Sawyerr 01, Garvin PJ. Codd JE, et al: Colorectal complications of renal allograft transplantation. Arch Surg I l3:84 86. 1978 35. Spanos PK, Simmons RL, ulcer disease in the transplant 109:193 197,1974

Rattarzi LC, et al: Peptic recipient. Arch Surg

36. Sutherland D, French RS, Weil R, et al: The bleeding cecal ulcer: Pathogenesis, angiographic diagnosis, and nonoperative control. Surgery 71:290 294, 1972 37. Thompson WM, Seigler HF, perforation: A complication following Am J Roentgen01 125:723-730, 1975 38. Woods JE, Anderson Pancreatitis in renal allografted 47:193 195, 1972

Rice RP: Ileocolonic renal transplantation.

CF. Frohnert patients. Mayo

PP, et al: Clinic Proc