Polyomavirus infection in pediatric renal transplant recipients: Evaluation using a quantitative real‐time PCR technique

Abstract

Polyomavirus infection and related nephropathy is being increasingly recognized as an important cause of allograft dysfunction in adult renal transplant recipients. We prospectively monitored pediatric renal transplant recipients for the presence of BK and JC polyomavirus in urine and blood using a quantitative PCR assay to evaluate the prevalence and clinical relevance of polyomavirus infection in the pediatric renal transplant population. Of 46 pediatric renal recipients who were evaluated, nine (20%) demonstrated isolated BKV viruria, while five (11%) had concomitant BKV viremia and viruria. JCV viruria was found in eight (17%) patients. BKV viremia was associated with a significantly higher urinary BKV viral load: median urinary viral load 1.9 x 10(9) copies/mL (range 6.7 x 10(2)-1.8 x 10(11)) for the group with concomitant viremia and viruria vs. 1.8 x 10(3) copies/mL (range 2.5 x 10(2)-4.5 x 10(6)) for the group with isolated viruria (p < 0.0001). In children that were followed prospectively since their transplantation, the BKV urinary viral load increased markedly before viremia became detectable a few weeks later. None of the patients with JCV viruria or isolated BKV viruria had renal dysfunction. Among the five patients with BKV in both urine and blood, two developed biopsy-proven BKV nephropathy associated with deterioration of the renal function. Management of the BKV nephropathy consisted of reduction of immunosuppression alone or in combination with antiviral treatment with cidofovir. This study shows that polyomavirus infection and related interstitial nephritis is a relevant clinical issue in the pediatric renal transplant population. Monitoring the polyomaviral load in the urine and the blood of the patients using a quantitative PCR technique is a useful tool in the diagnosis and subsequent management of this infection. Even before viremia is present, an important rise in the urinary viral load should draw the attention of the transplant clinician and raise the issue of adapting the immunosuppression.

Progressive Multifocal Leukoencephalopathy after Natalizumab Therapy for Crohn's Disease

“…We performed a quantitative real-time polymerase-chainreaction assay using primers specific for JC virus (PEP3 and PEP6), as described previously. 6 No viral DNA was detected in serum obtained at multiple times from April 1999 through February 2003 (Table 1) or in the fresh-frozen intestinal samples obtained at surgery in 2000 while the patient was being treated with several potentially immunosuppressive drugs. However, JC virus DNA was detected in a serum sample obtained two months before admission, while the patient was receiving monthly infusions of 300 mg of natalizumab, and had increased by a factor of 12 by the time the patient was admitted (Table 1).…”

Polyomaviruses KI and WU in Immunocompromised Patients with Respiratory Disease

“…Specimens positive for KIPyV or WUPyV were tested for adenoviruses; human bocavirus; human rhinoviruses; human metapneumovirus; human coronaviruses OC43, 229E, NL63, HKU1; and human PyVs BK and JC by using PCR methods (6)(7)(8)(9)(10)(11). Total nucleic acid was extracted from 200 μL of NA, BAL, or stool specimens by using the EasyMag System (bioMérieux, Marcy l'Etoile, France).…”

Internally Controlled Triplex Quantitative PCR Assay for Human Polyomaviruses JC and BK

“…A number of qPCR assays for human PyV have been reported. However, these assays are typically designed to amplify and quantify either BKPyV (23) or JCPyV (9, 10) alone or to detect both viruses but in separate assays (17,28,29,34). Other assays have combined the detection of JCPyV and BKPyV into a single reaction.…”

“…Furthermore, BKPyV can cause fatal meningoencephalitis in AIDS patients (1) and has been found in the cerebrospinal fluid (CSF) of patients with central nervous system disease (12). In addition, the simultaneous reactivation of JCPyV and BKPyV in patients with renal disease has been reported (17).…”

“…For example, reactivation of BKPyV is associated with hemorrhagic cystitis in bone marrow transplant recipients (22,24,25) and can also cause transplant organ failure in renal transplantation patients receiving immunosuppressive therapy (7,17,23,26,30,33). The reactivation of JCPyV is associated with the development of progressive multifocal leukoencephalopathy, a fatal condition associated with AIDS-related immunosuppression (13,20,35).…”