What are the causes of fever in a patient with end-stage renal disease (ESRD) undergoing hemodialysis?

Causes of Fever During Hemodialysis

Fever during hemodialysis most commonly results from catheter-related bloodstream infection (CRBSI), particularly in patients with central venous catheters, followed by dialysis-related complications including myocardial ischemia, pericarditis, and less commonly, graft intolerance syndrome in transplant patients or cryoglobulinemic vasculitis. 1, 2, 3

Primary Infectious Causes

Catheter-Related Bloodstream Infection (CRBSI)

• CRBSI is the leading cause of fever in hemodialysis patients, with bacteremia rates reaching 31.7% in febrile dialysis patients presenting to emergency departments. 3
• Patients using dialysis catheters have 6.55 times higher odds of bacteremia compared to those with arteriovenous fistulas or grafts (OR 6.55,95% CI 3.96-10.8). 3
• The most common organisms isolated include non-MRSA Staphylococcus aureus (40.7%), MRSA (13.3%), Pseudomonas aeruginosa (11.5%), and Enterobacter species (11.5%). 3
• In failed kidney transplant patients with catheters, 38% of fevers are due to dialysis catheter-associated infections. 1

Other Infection Sources

• Pneumonia and other pulmonary infections represent significant causes requiring chest imaging and appropriate antimicrobial therapy. 1, 4
• Infective endocarditis should be considered in high-risk patients, particularly those with prior cardiac procedures, prosthetic valves, or recurrent bacteremia, requiring transesophageal echocardiography for diagnosis. 4
• Uncommon pathogens including Cutibacterium acnes, Corynebacterium accolens, and viral pathogens like Epstein-Barr virus may be identified through metagenomic next-generation sequencing when conventional cultures remain negative. 4

Cardiovascular and Dialysis-Related Causes

Myocardial Ischemia

• Acute myocardial infarction or ischemia induced by intradialytic hypotension or tachyarrhythmias is a frequent serious cause of fever and chest pain during dialysis. 1
• Hypotension during dialysis can precipitate myocardial ischemia in patients with underlying coronary artery disease. 1
• A 12-lead ECG should be obtained immediately, and patients with acute unremitting chest pain during dialysis require transfer by EMS to an acute care setting. 1

Pericarditis

• Uremic pericarditis occurs in approximately 5% of patients starting dialysis, while dialysis pericarditis affects 2-21% of established dialysis patients. 1
• Up to 30% of patients with uremic pericarditis are asymptomatic, and ECG abnormalities are often absent due to lack of myocardial inflammation. 1
• Fever may be present alongside chest pain, though typical pleuritic pain occurs less frequently than in non-uremic pericarditis. 1

Hemolysis and Equipment-Related Issues

• Hemolysis from dialysis equipment malfunction can present with fever, chest pain, and acute symptoms during treatment. 1
• Pulmonary embolism, though less common, must be considered in the differential diagnosis of fever with dyspnea during dialysis. 1

Immunologic and Inflammatory Causes

Graft Intolerance Syndrome (in Transplant Patients)

• In patients with failed kidney transplants undergoing dialysis, graft intolerance syndrome causes fever in 30-50% within 1 year of allograft failure and dialysis initiation. 1
• Fever occurs alongside graft tenderness, enlargement, gross hematuria, and elevated inflammatory markers (CRP, ESR, ferritin). 1
• Patients with failed grafts have a 7-fold higher risk of hospital admissions for febrile illnesses without identified infection within 6 months of immunosuppression withdrawal. 1
• Among failed allograft patients presenting with fever, 62% have rejection as the source, while 38% have infection (most commonly dialysis catheter-associated). 1

Cryoglobulinemic Vasculitis

• Cryoglobulin sensitization by cold dialysate temperature can cause recurrent fever specifically after hemodialysis sessions. 5
• This diagnosis should be considered when fever occurs exclusively post-dialysis and can be managed by increasing dialysate temperature to 37.5°C and plasma exchange. 5
• Associated manifestations may include alveolar hemorrhage mimicking pneumonia. 5

Risk Stratification for Bacteremia

High-Risk Features

• Presence of central venous catheter for dialysis access (OR 6.55). 3
• Prior history of bacteremia (OR 8.87). 3
• Greater than 5% neutrophilic band cells (OR 3.32). 3
• Fever during or after dialysis (OR 1.6 for bacteremia). 6
• Chills during hemodialysis indicate 60.2% rate of infection and 33.5% rate of bacteremia. 6

Lower-Risk Features

• Patients with arteriovenous fistula or graft (not catheter) as access, without fever, normal leukocyte count, and normal albumin have only 6% risk of bacteremia. 6
• These lower-risk patients may be investigated without immediate empirical antibiotics. 6

Critical Diagnostic Pitfalls

• Not all fevers in dialysis patients are infectious—infections, malignancies, and rejection must all be ruled out systematically. 1
• Patients with end-stage renal disease may be euthermic or hypothermic despite life-threatening infection, particularly elderly patients, those with open wounds, burns, or receiving continuous renal replacement therapy. 1
• Other signs of infection in afebrile patients include unexplained hypotension, tachycardia, confusion, rigors, leukocytosis, leukopenia, >10% band forms, or thrombocytopenia. 1
• Conventional blood cultures may remain negative despite true infection, requiring advanced diagnostics like metagenomic next-generation sequencing. 4

Immediate Management Approach

• Obtain blood cultures from both catheter lumens and peripheral sites before initiating antibiotics. 3, 6
• Perform 12-lead ECG to evaluate for myocardial ischemia. 1
• Initiate empirical broad-spectrum antibiotics immediately in high-risk patients (catheter access, prior bacteremia, fever with leukocytosis, or chills) following culture collection. 3, 6
• Consider transesophageal echocardiography in patients with recurrent bacteremia, prior cardiac procedures, or persistent fever despite appropriate antibiotics. 4
• Rule out graft intolerance syndrome in transplant patients before attributing fever to infection. 1