title: [BK virus infections in pediatric kidney transplant recipients].
abstract: Primary BK virus (BKV) infections acquired mainly during childhood are usually asymptomatic. Several studies revealed its seroprevalence in adult population as high as 90% worldwide. Following primary infection, virus persists as latent infection in the urogenital tract. In renal transplant recipients, primary infection and reactivations affect 10% of patients and without treatment, more than half of these patients lose their grafts. The only way of preventing graft loss due to BKV nephropathy (BKVN), seems to monitor BKV infection after transplantation and to diagnose patients developing BKVN during the early period and treat them accordingly. In this study, we analyzed BKV presence in plasma and urine samples with real-time PCR method and evaluated the renal biopsies of pediatric renal transplant recipients after transplantation, retrospectively. A total of 142 children (63 female, 79 male; mean age: 11.7 ± 3.9 years) who had renal transplantation in Akdeniz University Medical Faculty, Antalya, Turkey, between February 2006 and April 2011 were enrolled in the study. After transplantation, peripheral blood and urine samples were collected bi-weekly for the first three months, monthly till the sixth month and every three months thereafter. BKV DNA was additionally screened in patients with unexplained rise in serum creatinine or in patients receiving anti-rejection therapy. In any plasma positivity or during the BKVN therapy, BKV DNA analysis was done bi-weekly. After DNA extraction by automated system, an 83 base pair fragment in VP1 region was amplified. Signal detection for the target region was performed with a TaqMan probe dual-labelled at the 5' end with 6-carboxyfluorescein (FAM) and the 3' end with 6-carboxytetramethylrhodamine (TAMRA). Histopathological examinations of renal biopsies were done with routine histological stains and immunohistochemical staining with monoclonal antibodies directed to SV40 antigen. From 2171 plasma and 1995 urine samples without PCR inhibitors, 442 (20%) (range: 300-4.5 x 10(7) copies/ml; mean: 2.0 x 10(5) ± 2.2 x 10(6) copies/ml) and 800 (40.1%) (range: 300-3 x 10(12) copies/ml; mean: 5.9 x 10(9) ± 1.1 x 10(11) copies/ml) were found positive for BKV DNA, respectively. For 114 (80.3%) patients, at least one urine sample was positive and more than half of those patients (68/114, 59.6%) had viremia. Of the patients, 19.7% (28/142) had viral DNA above 10(4) copies/ml, which was choosen as a cut-off value for its high positive predictive value for BKVN. For all these 28 patients, prior to renal biopsy, immunosupressive treatment was decreased. Cidofovir and/or leflunomid were initiated to nine patients who did not respond to lowered immunosupressive therapy and eight of them had renal biopsy for the confirmation of BKVN. All renal biopsy results were compatible with BKVN. From these nine patients who were receiving cidofovir and/or leflunomid, two lost their grafts because of BKVN. Since viruria is frequently encountered and the viral load is usually in low quantities and transient, it is more appropriate to use blood samples for screening programmes after renal transplantation. The efficacy of antiviral treatment in BKVN could not be evaluated since it was only applied in patients non-responding to lowered immunosuppressive therapy and had decreased renal functions. Multicenter prospective studies are required to enlighten this important issue. Early diagnosis with close monitoring of renal function and viremia, seems to be the most effective way for controlling BKVN.
authors: Akdeniz University Medical School Hospital, Department of Medical Microbiology, Antalya, Turkey. dcolak@akdeniz.edu.tr.
authors: Derya
authors: D
authors: Mutlu
authors: Imran
authors: I
authors: Sağlık
authors: Mustafa
authors: M
authors: Koyun
authors: Elif
authors: E
authors: Comak
authors: Esvet
authors: E
authors: Mutlu
authors: Arife
authors: A
authors: Uslu Gökçeoğlu
authors: Serpil
authors: S
authors: Cağla Doğan
authors: Ayhan
authors: A
authors: Dinçkan
authors: Sakine Halide
authors: SH
authors: Akbaş
authors: Bahar
authors: B
authors: Akkaya
authors: Sema
authors: S
authors: Akman
authors: Gültekin
authors: G
authors: Süleymanlar
authors: Dilek
authors: D
authors: Colak
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000627:therapeutic use; D001739:BK Virus / Q000235:genetics / Q000302:isolation & purification; D002648:Child; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007555:Isoxazoles / Q000627:therapeutic use; D007674:Kidney Diseases / Q000453:epidemiology* / Q000209:etiology / Q000628:therapy; D016030:Kidney Transplantation / Q000009:adverse effects; D000077339:Leflunomide; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use; D027601:Polyomavirus Infections / Q000453:epidemiology* / Q000209:etiology / Q000628:therapy; D014412:Tumor Virus Infections / Q000453:epidemiology* / Q000209:etiology / Q000628:therapy; D014421:Turkey / Q000453:epidemiology
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D063065:Organophosphonates; D003596:Cytosine; D000077339:Leflunomide; D000077404:Cidofovir