Cytomegalovirus Nephritis

Cytomegalovirus Nephritis
Anthony Chang, MD
Key Facts
Terminology
  • CMV infection in kidneys, usually associated with systemic CMV in immunocompromised patient
Etiology/Pathogenesis
  • Cytomegalovirus
  • Immunocompromised patients at risk
Clinical Issues
  • Presentation
    • Renal dysfunction
    • Flu-like symptoms
  • Antiviral agents
    • Ganciclovir or valganciclovir
    • CMV immune globulin
  • Reduce or alter immunosuppressive agents
Microscopic Pathology
  • Nuclear inclusions
    • Most prominent in tubular epithelium
    • Glomerular capillary &/or peritubular capillary endothelial cells
  • Interstitial inflammation, mononuclear
  • Acute glomerulonephritis (rare)
Top Differential Diagnoses
  • Polyomavirus nephropathy
  • Adenovirus tubulointerstitial nephritis
  • Acute cellular rejection
  • Acute allograft glomerulopathy (form of rejection)
Diagnostic Checklist
  • Coinfection with other fungal or viral organisms may occur
Hematoxylin & eosin shows characteristic intranuclear (“owl’s eye”) inclusions image of CMV infection within the glomerular endothelial cells.
Hematoxylin & eosin shows CMV intranuclear inclusions image in endothelial cells of a peritubular capillary with basophilic cytoplasmic changes image that are also present in a tubular epithelial cell image.
TERMINOLOGY
Abbreviations
  • Cytomegalovirus (CMV) nephritis
Synonyms
  • CMV tubulointerstitial nephritis (TIN)
  • CMV nephropathy
  • CMV glomerulonephritis
Definitions
  • Direct CMV infection of kidneys, usually associated with systemic CMV involvement and immunocompromise
    • CMV may promote indirect effects on kidney, particularly in renal transplants, including acute allograft glomerulopathy
ETIOLOGY/PATHOGENESIS
Infectious Agents
  • Cytomegalovirus (human herpesvirus-5 [HHV-5])
    • Family Herpesviridae
      • β-subfamily
      • Double-stranded DNA virus
Risk Factors
  • Immunocompromised patients at risk for systemic CMV
    • Transplant recipients on immunosuppression
      • Transplant CMV from donor organ or reactivation in recipient
      • Matching CMV serologic status in renal transplant patients has minimized incidence of CMV TIN
    • Infants
      • Neonatal CMV infection from maternal transmission
    • HIV-infected patients
  • Causes benign, self-limited mononucleosis syndrome in normal individuals
Site of Infection
  • Epithelium, endothelium, monocytes
  • Renal involvement almost always associated with systemic infection
    • Lungs, liver, adrenals, retina, GI tract, epididymis, pancreas, bone marrow
Latent Virus
  • Most individuals infected before adulthood
    • Benign self-limited disease in normal individuals
    • Seroprevalence (90%)
    • Virus remains present in latent state for life
Effects on Immune System
  • Increased IL-6 and IL-10, decreased Th1 cytokines (interferon-γ)
  • Decreased expression of HLA antigens
CLINICAL ISSUES
Epidemiology
  • Incidence
    • Neonatal CMV
      • Most common neonatal infection
      • 0.2-2% of live births in USA
      • 9.4 per 100,000 infants ages 1-4 years in Australia
    • Transplant CMV
      • ˜ 20% incidence of CMV disease with ganciclovir prophylaxis
      • ˜ 45% incidence without prophylaxis
      • Frequency of CMV infection in renal transplant biopsies < 1%
  • Age
    • Neonatal, intrauterine
    • Immunocompromised adults
  • Gender
    • Male predilection
  • Ethnicity
    • No ethnic predilection
Presentation
  • Fever
  • Malaise
  • Leukopenia
  • Renal dysfunction
  • Acute renal failure
  • Proteinuria
Laboratory Tests
  • CMV IgM antibodies
    • Suggest recent or active infection
    • False positives due to rheumatoid factor
  • CMV IgG antibodies
    • Suggests chronic/latent infection
  • CMV antigen test
    • Indirect IF test to detect pp65 protein of CMV in peripheral blood leukocytes
  • CMV polymerase chain reaction (PCR)
  • Viral culture
    • Shell vial assay
Treatment
  • Drugs
    • Ganciclovir or valganciclovir
      • Prophylaxis
      • Intravenous therapy
    • Foscarnet
      • Side effects include crystal formation leading to glomerulopathy
      • Multinucleation of tubular epithelial cell nuclei may persist after foscarnet therapy
    • Cidofovir
    • CMV intravenous immune globulin (IVIG)
  • Reduce or alter immunosuppressive agents
  • Vaccination to prevent maternal transmission
Prognosis
  • Neonatal CMV
    • 30% mortality among symptomatic infants
    • Survivors commonly have neurologic deficits
  • CMV disease in transplant recipient
    • Increased graft loss in past (10-20%)
    • Less adverse effect of CMV in patients on current immunosuppressive protocols
MICROSCOPIC PATHOLOGY
Histologic Features
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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Cytomegalovirus Nephritis

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