Acute tubulointerstitial nephritis: possible association with cytomegalovirus infection

Abstract

Sirs, A previously healthy 14-year-old boy presented with mild acute renal dysfunction with proteinuria and glucosuria. His past history and family history were unremarkable. The ophthalmologic examinations were normal. The patient was taking no medicines. Blood urea nitrogen of 18 mg/dl, creatinine of 1.3 mg/dl and creatinine clearance of 107.4 ml/min/1.73 m 2 were all measured. An autoantibody screen was negative. Urinary excretion of N-acetyl-beta-glucosaminidase (NAG) was 63.2 U/l (normal 0.3-11.5 U/l), and b2-microglobulin (b2-MG) was 37,079 g/l (normal 30-340 g/l). Serological tests for Epstein-Barr virus (EBV) showed the following: EBVviral capsid antigen (VCA) IgG 80x (negative <10x); VCA IgM <10x; early antigen-diffuse and restricted antibody (EA-DR) IgG <10x; EBV-nuclear antigen (EBNA) <10x. A cytomegalovirus (CMV)-specific IgM antibody showed a 1.27 index (negative <0.49 index) and a CMVspecific IgG avidity of 152 arbitrary units/ml (AU/ml; negative <14.9 AU/ml). Other serological results for hepatitis B, C, mycoplasmal pneumonia and syphilis were negative. Serial urine cultures showed no pathogens. A renal biopsy specimen showed marked lymphocytic tubulointerstitial nephritis (TIN) with tubular epithelial lesions and intratubular hyaline casts. The 30 glomeruli evaluated were completely normal, as were the blood vessels without granulomas and interstitial fibrosis. Immunofluorescent studies were negative. Immunohistochemical tests for CMV and EBV were negative. Mononuclear infiltration consisted mainly of CD3-positive lymphocytes with some CD8-positive T-cells and in small numbers of B-cells. Electron microscopy showed no evidence of viral inclusions. A CMV polymerase chain reaction (PCR) assay on peripheral blood was negative. Virus isolation from urine was not performed. The patient was given oral prednisolone (40 mg/day, 1 mg/kg/day, daily) with imidapril hydrochloride (5 mg/day) and showed a complete recovery. After rapid improvement of the clinical and laboratory signs of TIN, prednisone was tapered off over a period of 6 months without a flare-up of TIN.Acute TIN is a heterogeneous disorder that is caused by infectious agents, immunological disorders and idiopathic type. The patient had not taken nonsteroidal antiinflammatory drugs or any herbal or alternative medicines. The autoimmune screen and complement concentrations were normal, excluding autoimmune systemic diseases. Congenital and neonatal acute TIN is well known to be associated with CMV [1]. Recently, Kaminska et al. reported a case of CMV-associated TIN in a 15-year-old girl with positive CMV antigens in the kidney biopsy specimen [2]. Direct evidence of renal involvement with CMV infections is rarely seen. At the time of virus detection, CMV might have already disappeared from the targeted organ of the patient because older children and adults can rapidly eradicate CMV. Our case confirms CMV-related TIN only in part because the patient showed no symptoms of systemic CMV infection except for a fever, but the presence of IgM CMV antibo...

Membranous nephritis associated with acquired cytomegalovirus infection in a 19-month-old baby

“…All of the reported cases were treated with ganciclovir, which was discontinued in one patient due to its side effects [19][20][21]. There are also two reports of pediatric patients, a 3-month old baby and a 14-year-old boy, with interstitial nephritis associated with CMV infection [22,23]. Το the best of our knowledge, we report here the first published case of biopsy-proven, CMV-related membranous glomerulonephritis in an immunocompetent child.…”

Analysis of the shedding of three β‐herpesviruses in urine and saliva of children with renal disease

“…CMV has been implicated in nephritis and rejection in renal transplant recipients [De Keyzer et al, 2011]. Additionally, it has been suggested that CMV may be involved in childhood nephritis [Platt et al, 1985;Matsukura et al, 2006;Georgaki-Angelaki et al, 2009] and congenital nephrotic syndrome [Evans and Lyon, 1991;Batisky et al, 1993;Giani et al, 1996;Eddleston et al, 1997;Barbi et al, 1998;Frishberg et al, 2003;Besbas et al, 2006]. Since children with renal disease are treated generally by immunosuppressive drugs, these patients are considered to be at high risk for reactivation of herpesviruses.…”

An unusual renal manifestation of chronic HBV infection

“…TIN is a heterogeneous disorder caused by infection, immunological disorders or drugs. Infection by a wide range of organisms is the most common cause of TIN [ 8 ]. Human immunodeficiency virus, cytomegalovirus, Epstein–Barr virus, Hanta virus, Polyoma and adenovirus are some of the viruses associated with TIN.…”