#3822 POLYOMAVIRUS INFECTION MONITORING BY QUANTITATIVE PCR IN KIDNEY RECIPIENTS AS AN INSTRUMENT FOR PREVENTING POSTTRANSPLANT COMPLICATIONS

Abstract

Abstract Background and Aims Polyomaviruses (PyV) are ubiquitous human viral pathogens. BKV and JCV representing this viral family are common causative agents of viral complications among kidney recipients. Viral load higher than 1 × 107 copies/ml in urine (viruria) or 1 × 104 copies/ml in serum (viremia) in posttransplantation period may lead to polyomavirus-associated nephropathy (PVAN), hemorrhagic cystitis (HC) or even kidney transplant failure. The aim of the study was to assess PyV reactivation frequency in patients during 12 months after renal transplantation (RT) and to identify molecular subtypes of BKV and JCV. Method We examined 3207 samples of biological material (serum and urine) of 763 adult (>18 years) patients who underwent renal transplantation (RT) at the State Institution “Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology”, Healthcare institutions “Brest Regional Clinical Hospital”, “Vitebsk Regional Clinical Hospital Belarus”, “Mogilev Regional Clinical Hospital”. These patients were divided into 2 groups: group 1 included 394 patients examined only for BKV infection, group 2 – 356 recipients examined for both BKV and JCV infection. Serum and urine samples for regular monitoring were collected from patients before RT, every 2 weeks first 3 months, then at 6, 9, 12 months after RT. In the case of complication development samples from patients were collected later then 1-year monitoring period. PyV DNA was detected by real-time PCR. Viral DNAs from 17 BKV-positive and 11 JCV-positive patients were molecular typed by partial sequencing of VP1 genome region. Confidence intervals for the proportions were calculated using Wald's method. Results Results showed that BKV detection total frequency in the group 1 was 14.47% [11.32%; 18.3%], almost all patients developed viruria, only 2.54% [1.32%; 4.67%] had viremia. In the group 2 PyV DNA was detected in 46.07% [40.96%; 51.26%] of recipients: 19.10% [15.34%; 23.52%] had BKV infection, 19.94% [16.11%; 24.42%] – JCV, 7.02% [4.76%; 10.2%] – BKV+JCV mixed infection. Frequency of viremia was 6.74% [4.53%; 9.87%] in this group. Maximal BKV viral load levels reached 1.2 × 1012 copies/ml in urine and 5.9 × 107 copies/ml in serum. JCV loads were up to 3 × 109 copies/ml in urine and 1.2 × 108 copies/ml in serum. Then we analyzed frequency of PyV detection before RT and during the first year after RT among the 102 recipients. Results displayed on the Fig. 1 showed that the peak of PyV infection registration and the higher risk for patient had a place on the 1.5-2.5 months after RT. Quantitative monitoring of viral load in posttransplant period was the basis for the correction of the applied immunosuppressive therapy regimens in relation to the recipients with a high viral load (higher than 1 × 107 copies/ml in urine or 1 × 104 copies/ml in serum). The results of molecular typing showed that 17 BKV isolates belonged to subgroups Ib-2 and IVc-2 (12 and 5 isolates, respectively). Within subgroups Ib-2 isolates formed 3 clusters corresponding 3 separate genovariants. JCV isolates belonged to subtype 1A, 1B and 2A (7, 3 and 1 of isolates, respectively). The last one had 99% nucleotide sequence similarity with Greece and South Korea isolates. Conclusion Our data demonstrated an importance of PyV DNA monitoring of kidney recipients in the posttransplant period starting from the first days after RT to predict development of PyV complications as PVAN, HC or others by correcting the immunosuppressive therapy.