Comparing Urine and Blood Screening Methods to Detect BK Virus After Renal Transplant.

OBJECTIVES: BK polyomavirus can infect healthy individuals; however, in renal transplant recipients, it can cause nephropathy, which can lead to renal allograftfailure. There are currently no effective antiviral agents against BK polyomavirus. Surveillance after kidney transplant for BK polyomavirus is the only means to prevent allograft failure. Transplant centers routinely screen for BK polyomavirus in either urine or blood. If BK polyomavirus replication occurs, itis usually detected first in urine, which is followed by detection in blood in a subset of cases. Screening for BK polyomavirus in urine has the potential for earlier detection of viralreactivation.However, not all patients with BK polyomavirus in urine will progress to BK viremia. Therefore, adding urine screening could increase the cost oftests without a clear clinical benefit. MATERIALS AND METHODS: We conducted an analysis of BK polyomavirus screening methods at 2 different centers and compared their clinical outcomes and efficiency of testing. RESULTS: We analyzed 209 patientswith BK polyomavirus reactivation after kidney transplant at 2 different institutions from 2008 to 2018. BK polyomavirus reactivation in blood was detected earlierifthe patient was screened by urine screening protocol. However, measurable clinical outcomes were similarin all groups with different screening methods. CONCLUSIONS: Although screening for BK polyomavirus in urine did detect viralreactivation earlier,there were no differences in graft or clinical outcomes when either the urine or blood screening method was used.

NK Cells Contribute to the Immune Risk Profile in Kidney Transplant Candidates.

Background: A previously proposed immune risk profile (IRP), based on T cell phenotype and CMV serotype, is associated with mortality in the elderly and increased infections post-kidney transplant. To evaluate if NK cells contribute to the IRP and if the IRP can be predicted by a clinical T cell functional assays, we conducted a cross sectional study in renal transplant candidates to determine the incidence of IRP and its association with specific NK cell characteristics and ImmuKnow® value. Material and Methods: Sixty five subjects were enrolled in 5 cohorts designated by age and dialysis status. We determined T and NK cell phenotypes by flow cytometry and analyzed multiple factors contributing to IRP. Results: We identified 14 IRP+ [CMV seropositivity and CD4/CD8 ratio < 1 or being in the highest quintile of CD8+ senescent (28CD-/CD57+) T cells] individuals equally divided amongst the cohorts. Multivariable linear regression revealed a distinct IRP+ group. Age and dialysis status did not predict immune senescence in kidney transplant candidates. NK cell features alone could discriminate IRP- and IRP+ patients, suggesting that NK cells significantly contribute to the overall immune status in kidney transplant candidates and that a combined T and NK cell phenotyping can provide a more detailed IRP definition. ImmuKnow® value was negatively correlated to age and significantly lower in IRP+ patients and predicts IRP when used alone or in combination with NK cell features. Conclusion: NK cells contribute to overall immune senescence in kidney transplant candidates.

Pre-transplant immune factors may be associated with BK polyomavirus reactivation in kidney transplant recipients.

BK polyomavirus (BKPyV) reactivation in kidney transplant recipients can lead to allograft damage and loss. The elements of the adaptive immune system that are permissive of reactivation and responsible for viral control remain incompletely described. We performed a prospective study evaluating BKPyV-specific T-cell response, humoral response and overall T-cell phenotype beginning pre-transplant through one year post-transplant in 28 patients at two centers. We performed an exploratory analysis of risk factors for the development of viremia and viruria as well as compared the immune response to BKPyV in these groups and those who remained BK negative. 6 patients developed viruria and 3 developed viremia. BKPyV-specific CD8+ T-cells increased post-transplant in viremic and viruric but not BK negative patients. BKPyV-specific CD4+ T-cells increased in viremic, but not viruric or BK negative patients. Anti-BKPyV IgG antibodies increased in viruric and viremic patients but remained unchanged in BK negative patients. Viremic patients had a greater proportion of CD8+ effector cells pre-transplant and at 12 months post-transplant. Viremic patients had fewer CD4+ effector memory cells at 3 months post-transplant. Exploratory analysis demonstrated lower CD4 and higher total CD8 proportions, higher anti-BKPyV antibody titers and the cause of renal failure were associated BKPyV reactivation. In conclusion, low CD4, high CD8 and increased effector CD8 cells were found pre-transplant in patients who became viremic, a phenotype associated with immune senescence. This pre-transplant T-cell senescence phenotype could potentially be used to identify patients at increased risk of BKPyV reactivation.