Quantitative Analysis of the Correlation of Human Polyomavirus and Hematuria in Patients after Stem Cell Transplantation.

Objective: quantitative evaluation of viruria (DNA-uria) and hematuria in patients with SCT and analyze both relationship clinically.

Methods and Materials: two PCR assays for detecting viruses in clinical specimens are established: quantifying virus load by real-time PCR and distinguishing BKV and JCV by seminested PCR. Intensity of hematuria, that is the dominant sign of hemorrhagic cystitis, was assessed by urinestick and classified into 6 grades: negative (−), trace or 1–10 (+), 11–25 (++), 26–80 (+++), 81–200 (++++) erythrocytes in 1 milliliter urine, and macrohematuria (+++++). 531 urine specimens were collected from 41 patients with SCT. Data were analyzed through SPSS software package.

Results: Prevalence rate of polyoma viruria and hematuria following SCT were 80% and 73% in this study cohort and 45% and 20 % in urine specimens. No viral genomes were detected in DNA extracted from blood cells and plasma. BK, BK integrating with JC, JC and non-identified virus-variants, respectively, were shed in 15, 11, 3, 4 patients in urine and were detected in 99, 21, 32, 11 urine samples. Data of 25 patients with specimens collected before SCT showed that only 5 cases sheded polyoma virus in urine, comparing with 21 cases with polyoma viruria post-SCT, demonstrates significant difference (P<0.0001). Risk factors of polyoma viruria were not found. The median of maximal virus load was higher in male than female (2.1x10⁹ vs. 9.1x10⁶, P=0.031, Mann Whithney), and in patients with hemorrhagic cystitis than without (2.5 x10¹⁰ vs. 4.7x10⁷, P=0.043). There were no documents of hematuria pre-SCT. Recipients with stem cells originating from bone marrow underwent more frequently hematuria than from peripheral blood cells. This is likely due to more patients with standard conditioning therapy in BMT group (90% vs. 57%, P=0.032). The application of anti-thymocyte glolubin impacted likely on incidence of hematuria (88% vs. 47%, P=0.008). This is identical with the results of the study reported by Rabenau HF. The significant statistic relationship between polyoma viruria and hematuria is not available by defining entities as positive and negative. Indeed BK-viruria prevalence in 35% urine specimens containing erythrocytes >= ++ and in 17% urine specimens with negative and only trace red blood cells, while hematuria with amount of erythrocytes >=++ presented in 21% BK-viruria, nevertheless in 9% urine specimens with negative or non-amplifying virus-variants, 7% JC-viruria and 6% BK integrating with JC-viruria (P=0.016). Time conformability was observed in onset of most viruria and hematuria within 2^nd-3^rd weeks post SCT.

Conclusions: the course of SCT exerts explicitly impact on the reactivation of polyomavirus in urinary tract and BK-virus attribute likely to the onset of severer hematuria. Co-factors and pathogenesis are needed to continue exploring.