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

Tags:
Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Cytomegalovirus Nephritis

Full access? Get Clinical Tree
Get Clinical Tree app for offline access