Which type of viral hepatitis is most likely to cause acute kidney injury?

Hepatitis E Virus (HEV) Most Commonly Causes Acute Kidney Injury Among Viral Hepatitis Types

Hepatitis E virus is the viral hepatitis most strongly associated with acute kidney injury, causing glomerulonephritis in both immunocompetent and immunosuppressed patients through immune complex deposition and direct renal injury. 1

Mechanisms of HEV-Associated Renal Injury

HEV causes kidney injury through multiple pathogenic mechanisms:

• Glomerulonephritis patterns include membranoproliferative glomerulonephritis (with or without cryoglobulinemia) and membranous glomerulonephritis, documented primarily with HEV genotypes 1 and 3 1
• Immune complex formation leads to glomerular capillary basement membrane deposition, stimulating cytokine production and complement activation 2
• Direct viral presence has been demonstrated, with HEV RNA isolated from cryoprecipitate in patients with HEV-associated cryoglobulinemic glomerulonephritis 1
• Causality is strongly supported by renal function improvement and proteinuria reduction following HEV clearance, either spontaneously or with antiviral therapy 1

Clinical Presentation and Risk Factors

The renal manifestations of HEV infection have distinct characteristics:

• Renal impairment occurs during acute HEV infection in solid organ transplant recipients and chronically infected immunosuppressed patients 1
• Immunosuppressed patients (particularly those infected with HEV genotype 3) are at highest risk for developing glomerular disease 1
• Immunocompetent individuals can also develop membranoproliferative and membranous glomerulonephritis with HEV genotypes 1 and 3 1

Diagnostic Approach

When evaluating for HEV-associated kidney injury:

• Test for proteinuria in all patients with HEV infection, as recommended by EASL guidelines 1
• Consider renal biopsy in patients with acute or chronic HEV infection who develop new-onset proteinuria 1
• Monitor liver function tests, though notably, many patients with HEV-associated extrahepatic manifestations have only modest liver abnormalities or even normal LFTs 1

Management Recommendations

Treatment strategy should follow this algorithmic approach:

• Antiviral treatment is suggested for patients with chronic HEV infection and associated glomerular disease 1
• Monitor for spontaneous clearance in acute cases, as renal function may improve without intervention 1
• Reduce immunosuppression when feasible in transplant recipients with chronic HEV and renal involvement 1

Other Viral Hepatitis and Kidney Injury

While HEV has the strongest association, other hepatotropic viruses can affect the kidneys:

Hepatitis C Virus (HCV)

• Chronic HCV causes membranoproliferative glomerulonephritis (type I), usually with type II mixed cryoglobulinemia, as the most frequent renal lesion 1
• Dialysis-requiring AKI occurred in 1.12% of HCV hospitalizations, with rates increasing from 0.86% in 2004 to 1.28% in 2012 3
• Mortality impact shows twofold increased odds of in-hospital death when dialysis-requiring AKI complicates HCV hospitalization 3

Hepatitis B Virus (HBV)

• AKI develops in 60% of patients with HBV-related acute-on-chronic liver failure (ACLF) 4
• Risk factors include spontaneous bacterial peritonitis (odds ratio 6.214) and higher MELD scores (odds ratio 1.097 per point) 4
• Survival rates at 90 days are significantly lower in HBV-ACLF patients with AKI (26.7%) versus those without AKI (80.0%) 4

Acute Viral Hepatitis (Unspecified)

• Functional renal failure or acute tubular necrosis can occur in otherwise uncomplicated acute viral hepatitis, though the mechanism remains uncertain 5
• Mortality is substantial, with sepsis being the primary cause of death in these cases 5

Common Pitfalls to Avoid

• Do not overlook HEV testing in patients presenting with unexplained proteinuria or glomerulonephritis, even when liver function tests are normal or only mildly elevated 1
• Avoid assuming chronic HCV is the only hepatitis virus causing glomerular disease; HEV should be considered, particularly in immunosuppressed patients 1
• Do not delay antiviral therapy in chronic HEV with renal involvement, as evidence suggests causal relationship with potential for reversibility 1
• Remember to test for cryoglobulins in patients with HEV and renal disease, as cryoglobulinemia can complicate the clinical picture 1