INTRODUCTION — Gastrointestinal (GI) symptoms are reported in up to 80 percent of dialysis patients [1-3]. This topic reviews GI disorders that occur with a higher prevalence or have clinical features that are unique dialysis patients. We also discuss management considerations that are specific to GI diseases in patients on dialysis.
ESOPHAGUS AND STOMACH
Angiodysplasia — Angiodysplasias are the most common vascular anomalies encountered in the gastrointestinal (GI) tract. While their presentation and management are in most respects similar to those of the non-end-stage kidney disease (ESKD) population, patients with ESKD and chronic GI bleeding may benefit from estrogen therapy.
●Prevalence – Angiodysplasias account for approximately 20 and 30 percent of episodes of upper and lower GI bleeding, respectively, and for approximately one-half of recurrent episodes of upper GI bleeding in patients with ESKD [4]. It is unclear if the prevalence of angiodysplasia is higher among patients with ESKD as compared with the general population or if angiodysplastic lesions are detected more frequently in patients on hemodialysis due to exposure to anticoagulants and uremia-induced platelet dysfunction. (See "Angiodysplasia of the gastrointestinal tract" and "Angiodysplasia of the gastrointestinal tract", section on 'End-stage kidney disease'.)
●Clinical presentation and diagnosis – Patients usually present with chronic GI bleeding, although severe acute bleeding may also occur. Angiodysplastic lesions may also be found incidentally during endoscopic evaluation performed for other indications. The clinical presentation and diagnosis of angiodysplasia of the GI tract are discussed elsewhere. (See "Angiodysplasia of the gastrointestinal tract", section on 'Clinical manifestations' and "Angiodysplasia of the gastrointestinal tract", section on 'Diagnosis'.)
●Management – Patients on dialysis with chronic GI bleeding can benefit from administration of conjugated estrogens. Small case series have suggested that estrogens may prevent recurrent bleeding from angiodysplasia and reduce transfusion requirements [5,6]. The management of GI bleeding in patients on dialysis is otherwise similar to that for patients not on dialysis and is discussed in detail separately. (See "Approach to acute upper gastrointestinal bleeding in adults" and "Uremic platelet dysfunction".)
Esophageal varices — Patients on hemodialysis can rarely develop varices in the upper esophagus. These "downhill" esophageal varices, named after their downward direction of blood flow, result from superior vena cava (SVC) obstruction due to upper-extremity hemodialysis access [7-9]. Patients may be asymptomatic and discovered incidentally or present with upper GI bleeding. Definitive management involves treatment of the underlying SVC obstruction. However, in patients with severe upper GI bleeding, endoscopic therapy with variceal band ligation or sclerotherapy at the proximal end of the varix to temporize bleeding may be required prior to definitive treatment. (See "Overview of iliocaval venous obstruction" and "Malignancy-related superior vena cava syndrome" and "Central vein obstruction associated with upper extremity hemodialysis access".)
Gastroesophageal reflux — Patients on peritoneal dialysis have a higher incidence of symptomatic gastroesophageal reflux disease compared with patients on hemodialysis [10-13]. This higher incidence is due in part to increased intra-abdominal pressure from the presence of the dialysate in the peritoneal cavity, which may be further exacerbated by rapid accumulation of ultrafiltrate. In addition, most patients perform peritoneal dialysis while supine, which can contribute to reflux. This is often a challenging issue to resolve. Decreasing the fill volumes and lowering ultrafiltration goals may mitigate the rise in intra-abdominal pressure, but it would be at the cost of peritoneal dialysis adequacy.
Gastroparesis — Patients with ESKD are more likely to have gastroparesis; symptoms overlap with those of uremia. Typically, dialysis is optimized prior to an extensive work-up and management of gastroparesis.
●Epidemiology – The frequency of gastroparesis (delayed gastric emptying) in ESKD is higher as compared with the general population, possibly due to a higher frequency of diabetes mellitus and the use of medications that can affect gastric emptying [3,14-16]. In peritoneal dialysis patients, mechanical or neurogenic mechanisms triggered by the presence of intra-abdominal fluid have been implicated in delayed gastric emptying. (See "Noninfectious complications of continuous peritoneal dialysis".)
●Clinical presentation – Undiagnosed gastroparesis is an important cause of malnutrition in patients with ESKD [17]. Similar to nondialysis patients, patients with ESKD and gastroparesis can present with nausea, vomiting, abdominal pain, early satiety, postprandial fullness, bloating, and, in severe cases, weight loss. (See "Gastroparesis: Etiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
●Diagnosis – Because symptoms of gastroparesis, particularly early satiety, nausea, and vomiting, are similar to those of uremia, the dialysis prescription and delivered dialysis dose should be assessed prior to performing an extensive evaluation for gastroparesis. In addition, all medications should be carefully reviewed, and culprit medications discontinued, when possible. As an example, iron supplements frequently cause abdominal pain. Phosphate binders, alkali replacement in the form of sodium citrate or sodium bicarbonate, and some antihypertensive medications (eg, calcium channel blockers, clonidine) may cause nausea. The diagnostic evaluation for gastroparesis is the same as in the nondialysis population and is discussed separately. (See "Gastroparesis: Etiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Indications for initiation of dialysis in chronic kidney disease", section on 'Common indications'.)
●Management – The management of gastroparesis is presented elsewhere. (See "Treatment of gastroparesis".)
PANCREAS
Acute pancreatitis
●Epidemiology and risk factors – The risk of acute pancreatitis is higher among patients on dialysis as compared with the general population [18-24]. In a retrospective cohort study of 67,078 patients with end-stage kidney disease (ESKD), the cumulative incidence of acute pancreatitis at one, three, five, seven, and nine years after initiating dialysis was 0.6, 1.7, 2.6, 3.4, and 4 percent, respectively [18]. The risk of acute pancreatitis was higher among patients undergoing peritoneal dialysis as compared with hemodialysis (5.11 and 5.86 per 1000 person-years).
The etiology of acute pancreatitis in patients on dialysis is similar to that for patients not on dialysis. However, some risk factors may be more prevalent in patients on dialysis (eg, hypercalcemia due to hyperparathyroidism) [19,22,25-28] (see "Etiology of acute pancreatitis"). The risk of acute pancreatitis may be increased among patients on peritoneal dialysis by chronic exposure to specific dialysate solutions, such as high dextrose-containing dialysate (ie, 4.25 percent) [20-22]. By contrast, icodextrin was associated with a lower risk of acute pancreatitis in one study [29]. (See "Peritoneal dialysis solutions", section on 'Constituents'.)
Although dyslipidemia is highly prevalent in patients with kidney disease, triglyceride concentrations that are high enough to cause acute pancreatitis (>1000 mg/dL) are rare. (See "Etiology of acute pancreatitis" and "Hypertriglyceridemia-induced acute pancreatitis" and "Overview of the management of chronic kidney disease in adults" and "Overview of the management of chronic kidney disease in adults", section on 'Dyslipidemia'.)
●Clinical presentation and diagnosis – The symptoms of acute pancreatitis in patients on hemodialysis are similar to those in patients without kidney failure. Serum concentrations of pancreatic amylase and lipase are elevated in patients with ESKD in the absence of acute pancreatitis [24]. However, the absolute values generally do not exceed three times the upper limit of normal.
In patients on peritoneal dialysis, icodextrin-containing dialysate solutions interfere with the serum amylase assay, falsely lowering it [30]. For this reason, we use serum lipase rather than amylase for diagnosis of acute pancreatitis among such patients. It is also important to differentiate acute pancreatitis from microbial peritonitis in patients on peritoneal dialysis. The clinical presentation and diagnosis of acute pancreatitis and microbial peritonitis are discussed elsewhere. (See "Serum enzymes in patients with kidney failure", section on 'Pancreatic enzymes' and "Clinical manifestations and diagnosis of acute pancreatitis", section on 'Diagnosis' and "Approach to the patient with elevated serum amylase or lipase" and "Clinical manifestations and diagnosis of peritonitis in peritoneal dialysis", section on 'Differential diagnosis'.)
●Management – We use minimal heparin among patients on hemodialysis with acute pancreatitis to reduce the theoretical risk of hemorrhagic pancreatitis.
Peritoneal dialysis should not routinely be discontinued in all patients with acute pancreatitis and should only be halted if there is a high suspicion that the dialysate itself is the culprit. We suspect the dialysate is a cause of acute pancreatitis if the dialysis prescription had been recently changed preceding the onset of symptoms, particularly if the new prescription includes exchanges with high dextrose-containing dialysate (ie, 4.25 percent dextrose) or icodextrin. In such patients, we discontinue the 4.25 percent dextrose or icodextrin dialysate and continue peritoneal dialysis using a lower concentration of dextrose (ie, 1.25 or 2.5 percent dextrose). Peritoneal lavage can be helpful in removing inflammatory mediators. In addition, studies suggest that discontinuation of peritoneal dialysis does not improve outcomes in patients with acute pancreatitis [31].
●Prognosis – Some reports suggest that patients on dialysis with acute pancreatitis have a worse prognosis as compared with those without kidney disease [20,25,31].
As an example, in a study that compared outcomes among over 26,000 patients with acute pancreatitis, those receiving dialysis had a higher in-hospital mortality compared with those without chronic kidney disease (adjusted odds ratio 2.72, 95% CI 2.22-3.33) [32]. However, morbidity and mortality due to acute pancreatitis appear to be similar in patients undergoing hemodialysis or peritoneal dialysis [33].
Exocrine pancreatic insufficiency/chronic pancreatitis — ESKD has been implicated as a risk for chronic pancreatitis, possibly due to direct uremic toxicity. It is unclear if the prevalence of chronic pancreatitis is increased in hemodialysis patients; however, exocrine pancreatic insufficiency appears to be frequent in patients on hemodialysis [34]. In one study that included 50 patients with ESKD and no history of acute or chronic pancreatitis, mild-to-moderate exocrine pancreatic insufficiency was reported in 10 percent. (See "Exocrine pancreatic insufficiency".)
SMALL INTESTINE AND COLON
Intestinal ischemia — Mesenteric and colonic ischemia in the setting of hemodialysis is typically nonocclusive [35]. Risk factors in patients with end-stage kidney disease (ESKD) include older age, peripheral vascular disease, hypotension during hemodialysis, and prolonged hypotension following a hemodialysis session. (See "Nonocclusive mesenteric ischemia", section on 'Epidemiology and risk factors'.)
Patients with nonocclusive mesenteric ischemia may be asymptomatic or present with mild abdominal pain, bloating, nausea, or vomiting [36-38]. Patients with acute colonic ischemia usually present with the rapid onset of mild cramping abdominal pain. Rectal bleeding or bloody diarrhea usually develops within 24 hours. Patients on dialysis have more severe ischemic colitis and right-sided colitis as compared with nondialysis patients [39]. (See "Nonocclusive mesenteric ischemia", section on 'Clinical features' and "Colonic ischemia", section on 'Acute colonic ischemia'.)
Among patients undergoing peritoneal dialysis, the symptoms of ischemia may mimic those of peritonitis, resulting in a delay in diagnosis and a high mortality rate [40,41]. The diagnostic evaluation and treatment of patients with ischemic colitis and mesenteric ischemia are similar to those for the nondialysis population and are discussed in detail separately. (See "Colonic ischemia", section on 'Diagnosis'.)
Constipation/fecal impaction — Constipation and fecal impaction can occur secondary to the use of phosphate binders, analgesics, and iron in patients on dialysis. Patients on dialysis with a history of constipation should be advised to avoid aluminum-containing antacids and analgesics. In such patients, these medications can increase the risk of recurrent fecal impaction and aluminum toxicity. (See "Aluminum toxicity in chronic kidney disease", section on 'Aluminum-containing phosphate binders and antacids'.)
The management of constipation in dialysis patients is similar to that for the general population, with the exception that phosphate-containing laxatives are contraindicated in patients with kidney failure. Magnesium-containing antacids, such as milk of magnesia, should only be used if monitoring of the blood magnesium concentration is feasible. Lactulose may be the preferred laxative for chronic use in peritoneal dialysis patients [42]. The management of fecal impaction and constipation are discussed separately. (See "Constipation in the older adult", section on 'Management'.)
Acute diverticulitis — The frequency of diverticulosis is not increased in dialysis patients, except for those with underlying polycystic kidney disease [43-45]. However, the risk of acute diverticulitis may be increased in patients with ESKD [46]. The clinical presentation, diagnosis, and management of acute diverticulitis are the same as for non-ESKD patients. However, operative resection for diverticulitis is associated with a high mortality rate in older patients with ESKD [47]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations" and "Clinical manifestations and diagnosis of acute diverticulitis in adults" and "Acute colonic diverticulitis: Medical management".)
The incidence of fecal peritonitis is increased in all adult patients undergoing chronic peritoneal dialysis. Recurrent diverticulitis is a relative contraindication to peritoneal dialysis. However, if peritoneal dialysis is a preferred option for other reasons (ie, distance to hemodialysis center, poor vascular access, severe heart failure), then the risk/benefit discussion should include a discussion of fecal peritonitis. (See "Dialysis modality and patient outcome", section on 'Selection of dialysis modality' and "Patient survival and maintenance dialysis", section on 'Peritoneal dialysis'.)
A history of acute diverticulitis is an important consideration in transplant candidates since colonic perforation due to diverticulitis is associated with a high mortality rate [44]. In patients with indications for surgery (eg, extensive and/or recurrent symptomatic diverticular disease), resection is often performed electively prior to transplant.
Rare gastrointestinal diseases
●Dialysis-related gastrointestinal amyloidosis – Dialysis-related amyloidosis is rare and is related to the length of time on dialysis [48]. GI manifestations include GI bleeding, ischemic bowel perforation, and colonic pseudo-obstruction. (See "Dialysis-related amyloidosis" and "Gastrointestinal amyloidosis: Clinical manifestations, diagnosis, and management".)
●Intestinal necrosis – Sodium polystyrene sulfonate (SPSS), a cation exchange resin commonly used for the treatment of hyperkalemia in patients with kidney failure, has been associated with intestinal necrosis, ulceration, perforation, and mesenteric vascular thrombosis [49]. SPSS-associated intestinal necrosis is discussed in detail separately. This adverse effect does not appear to be associated with the newer intestinal potassium binders, patiromer and sodium-zirconium cyclosilicate. (See "Treatment and prevention of hyperkalemia in adults", section on 'Do not use sodium polystyrene sulfonate (SPS) or other resins'.)
●Spontaneous colonic perforation – Among ESKD patients, spontaneous colonic perforation can occur in association with aluminum-containing antacids, barium contrast, fecal impaction, or dehydration [50,51]. However, the etiology is unknown in many dialysis patients. The diagnosis must be considered in patients presenting with acute abdominal pain. (See "Overview of gastrointestinal tract perforation", section on 'Risk factors'.)
●Uremic colitis – Prior to the availability of maintenance dialysis, autopsy studies of patients with untreated uremia revealed extensive colonic ulcerations and pseudomembranes [50,52]. These findings, which were termed uremic colitis, are now rarely observed among hemodialysis patients.
Bowel preparation for lower gastrointestinal endoscopy — Bowel preparation with hyperosmotic laxative regimens (eg, sodium phosphate or magnesium citrate) should be avoided in dialysis patients. Such preparations can raise serum levels of phosphate or magnesium and provoke further loss of residual kidney function. Recommended preparations in patients with kidney function impairment (eg, polyethylene glycol-electrolyte lavage solution) are discussed in detail separately. (See "Bowel preparation before colonoscopy in adults", section on 'Patients with heart failure, renal insufficiency, end-stage liver disease, or electrolyte imbalances'.)
LIVER
Hemodialysis-associated ascites — Patients on maintenance hemodialysis can develop ascites in the absence of any other clear underlying cause.
●Epidemiology – The incidence of hemodialysis-associated ascites is not well established but appears to have declined due to improvement in hemodialysis technology, better control of volume overload, enhanced dialysis dose, and better nutrition.
●Pathogenesis and risk factors – Although the pathogenesis of hemodialysis-associated ascites is unclear, possible mechanisms include chronic volume overload with hepatic congestion and increased hepatic vein hydrostatic pressure, changes in the permeability of the peritoneal membrane in patients previously on peritoneal dialysis, and impaired lymphatic peritoneal resorption. Other contributing factors include hypoalbuminemia, congestive heart failure, and hyperparathyroidism [53-57].
●Clinical features and diagnosis – Clinical features include abdominal distension, cachexia, and symptoms of volume overload (eg, weight gain, shortness of breath, early satiety, and dyspnea) and malnutrition.
Ascitic fluid in patients with hemodialysis-associated ascites is clear and has a high protein content (3 to 6 g/dL) with a low serum ascites albumin gradient (<1.1) and neutrophil count. The diagnosis of hemodialysis-associated ascites is one of exclusion and requires an evaluation to rule out other causes of ascites. This evaluation is discussed in detail separately. (See "Evaluation of adults with ascites".)
●Management – The initial management of hemodialysis-associated ascites includes volume control with salt and fluid restriction, aggressive fluid removal by ultrafiltration, intermittent paracentesis, and improved nutritional intake [58]. However, hypotension may be a limiting factor in some patients. (See "Ascites in adults with cirrhosis: Initial therapy".)
If these initial measures fail to provide substantial benefit, switching to continuous ambulatory peritoneal dialysis (CAPD) may reduce the severity of ascites and improve nutritional status. Limited data suggest that placement of a peritoneovenous shunt (Denver or LeVeen shunt) may result in an improvement in hemodynamic stability and nutritional status and a reduction of ascites [59,60]. However, major complications of peritoneovenous shunt include infections and malfunction. (See "Hepatorenal syndrome", section on 'Peritoneovenous shunt'.)
Dialysis-associated ascites has a poor prognosis with a mortality rate of 45 percent within 15 months of diagnosis [61,62]. Kidney transplantation is the only definitive treatment, and complete resolution of ascites has been reported to occur within six weeks of transplantation in almost all patients [63,64]. However, not all transplant centers will perform transplantation in patients with recurrent ascites. (See "Ascites in adults with cirrhosis: Diuretic-resistant ascites".)
Hepatitis — The epidemiology, diagnosis, and treatment of hepatitis B virus and hepatitis C virus infection among patients on dialysis are discussed elsewhere. (See "Hepatitis C virus infection in patients on maintenance dialysis" and "Hepatitis B virus and dialysis patients" and "Treatment of chronic hepatitis C infection in adults with kidney function impairment".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)
SUMMARY AND RECOMMENDATIONS
●Gastrointestinal (GI) angiodysplasias account for approximately 20 and 30 percent of episodes of upper and lower GI bleeding in patients with end-stage kidney disease (ESKD). (See 'Angiodysplasia' above.)
●Hemodialysis patients can develop varices in the upper esophagus from superior vena cava (SVC) obstruction due to upper-extremity hemodialysis access. Patients may be asymptomatic and discovered incidentally or present with upper GI bleeding. Definitive management involves treatment of the underlying SVC obstruction. However, in patients with severe upper GI bleeding, endoscopic therapy with variceal band ligation or sclerotherapy at the proximal end of the varix may be needed to temporize bleeding prior to definitive treatment. (See 'Esophageal varices' above.)
●The prevalence of gastroparesis in ESKD is higher as compared with the general population, possibly due to a higher prevalence of diabetes mellitus and the use of medications that affect gastric emptying. Because symptoms of gastroparesis are similar to those of uremia, the dialysis prescription and delivered dialysis dose should be assessed prior to performing an extensive evaluation for gastroparesis. In addition, all medications should be carefully reviewed and culprit medications discontinued. (See 'Gastroparesis' above.)
●Dialysis patients have a higher risk of acute pancreatitis and a more severe clinical course. Risk factors for acute pancreatitis that are more prevalent in patients with ESKD include hypercalcemia due to hyperparathyroidism. In patients on peritoneal dialysis, risk may be increased by chronic local exposure to specific peritoneal dialysate solutions (eg, 4.25 percent dextrose and icodextrin). (See 'Acute pancreatitis' above.)
●Mesenteric and colonic ischemia in the setting of hemodialysis is typically nonocclusive and is frequently due to underlying hemodialysis-induced hypotension. Patients on dialysis have more severe ischemic colitis and right-sided colitis as compared with nondialysis patients. Among patients undergoing peritoneal dialysis, the symptoms of ischemia may mimic those of peritonitis. (See 'Intestinal ischemia' above.)
●Constipation and fecal impaction can occur secondary to the use of phosphate binders, analgesics, and iron. Magnesium and phosphate-containing laxative are contraindicated in patients with ESKD. (See 'Constipation/fecal impaction' above and 'Bowel preparation for lower gastrointestinal endoscopy' above.)
●Patients on maintenance hemodialysis can develop ascites in the absence of any other clear underlying cause. The diagnosis of hemodialysis-associated ascites is one of exclusion and requires an evaluation to rule out other causes of ascites. The initial management includes volume control with salt and fluid restriction, aggressive fluid removal by ultrafiltration, intermittent paracentesis, and improved nutritional intake. If initial measures fail, options include switching to continuous ambulatory peritoneal dialysis (CAPD) and placement of a peritoneovenous shunt. Kidney transplantation is the only definitive treatment. (See 'Hemodialysis-associated ascites' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Yousri M Barri, MD, who contributed to earlier versions of this topic review.
