Can hemodialysis (HD) cause diarrhea?

Can Hemodialysis Cause Diarrhea?

Hemodialysis itself does not directly cause diarrhea, but hemodialysis patients experience diarrhea frequently due to multiple indirect factors including medications (especially antibiotics causing C. difficile), phosphate binders, opioid-induced constipation with overflow diarrhea, and electrolyte disturbances related to dialysis treatment. 1

Primary Mechanisms of Diarrhea in HD Patients

Medication-Related Causes (Most Common)

• C. difficile infection is the most common enteric cause of fever and diarrhea in dialysis patients, particularly those who received antibiotics or chemotherapy within 60 days before diarrhea onset, accounting for 10-25% of all antibiotic-associated diarrhea cases. 1

• Testing for C. difficile toxin should be performed in any dialysis patient with diarrhea who has recent antibiotic exposure, as some patients may present with ileus, toxic megacolon, or leukocytosis without diarrhea. 1

• Medications requiring renal dose adjustment, such as acyclovir and gabapentin, are frequently prescribed at inappropriately high doses in dialysis patients, leading to adverse effects including gastrointestinal symptoms. 1

• Imipenem and other antibiotics can directly trigger C. difficile-associated diarrhea in hemodialysis patients, with temporal relationship between drug exposure and symptom onset. 2

Phosphate Binders and Constipation-Related Overflow

• Phosphate binders can cause both constipation and diarrhea, and when combined with opioids for pain management, they compound the risk of severe constipation with paradoxical overflow diarrhea. 1

• Dialysis patients frequently receive opioids for pain management, which commonly cause severe constipation, and when bowel regimens are discontinued, severe constipation can develop with paradoxical overflow diarrhea. 1

Dialysis-Specific Metabolic Factors

Electrolyte Disturbances

• Hypokalemia is a usual complication observed among hospitalized patients, with prevalence ranging from 12 to 20%, with reported values increasing up to around 25% in patients with kidney failure started on prolonged modalities of kidney replacement therapy. 3

• The risk of hypokalemia is proportional to the delivered dialysis dose and may be further augmented by the use of low-concentration potassium dialysis or replacement solutions, as well as by the coexistence of inadequate potassium intake or patients' comorbidities (e.g., diarrhea, metabolic alkalosis, diuretic therapy). 3

Nutritional and Metabolic Alterations

• Metabolic alterations associated with hemodialysis include loss of nutrients (amino acids, vitamins and carnitine), the induction of dialysis-related catabolism, and an increase in susceptibility to intercurrent acute conditions (infections). 3

• Anorexia is a major cause for the development of undernutrition in HD patients, and most HD patients eat much less than they should, with other "treatable" causes including acidosis, hyperparathyroidism and gastroparesis. 3

Prevalence and Clinical Impact

• Gastrointestinal symptoms are highly prevalent in people on dialysis, with constipation, indigestion, abdominal pain and reflux being the most commonly reported symptoms across both HD and PD modalities. 4

• Constipation was more common in HD patients than PD patients, while indigestion, abdominal pain and reflux were commonly reported in both dialysis modalities. 4

Critical Clinical Pitfalls to Avoid

• Volume depletion is a frequently identified risk factor for diarrhea-related deaths in all age groups, and diarrhea combined with excessive ultrafiltration from dialysis exchanges can rapidly cause hypovolemic shock, electrolyte imbalance, and metabolic acidosis. 1

• Other infectious causes, such as Salmonella, Shigella, Campylobacter, and STEC, are uncommon in dialysis patients unless present on admission or in outbreak settings, and sending stool cultures for routine bacterial pathogens or ova and parasites should generally be avoided unless the patient was admitted with diarrhea or is HIV-infected. 1

• Patients with end-stage kidney disease have a greater risk of developing C. difficile-associated diarrhea and ischemic colitis, which have clinical features that sometimes overlap with those of ulcerative colitis, emphasizing the importance of correctly diagnosing the etiology of intractable diarrhea. 5

Diagnostic Approach for Persistent Diarrhea

When evaluating diarrhea in HD patients, prioritize:

1. Review all medications for recent antibiotic exposure (within 60 days) and inappropriately dosed renally-cleared drugs. 1

2. Test for C. difficile toxin in any patient with recent antibiotic exposure or healthcare contact. 1

3. Assess for constipation-related overflow by reviewing opioid and phosphate binder use. 1

4. Consider colonoscopy with biopsy for intractable cases to rule out inflammatory bowel disease, ischemic colitis, or other structural causes. 5

Potential Therapeutic Interventions

• Synbiotic supplementation may promote improvement of chronic diarrhea of unknown etiology in hemodialysis patients, with one case report showing cessation of diarrhea episodes after three months of daily supplementation along with improved biochemical and nutritional parameters. 6

• Dialysis solutions containing potassium, phosphate, and magnesium should be used to prevent electrolyte disorders during kidney replacement therapy, which may indirectly reduce gastrointestinal complications. 3