Prediction of <scp>BK</scp> viremia by urine viral load in renal transplant patients: An analysis of <scp>BK</scp> viral load results in paired urine and plasma samples

Madden, Kathleen; Janitell, Charles; Sower, Daniel; Yang, Shangxin

doi:10.1111/tid.12952

Cited by 15 publications

(9 citation statements)

References 15 publications

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“…The rationale for performing biopsy only in the most severe cases with the highest BKV viral load and/or allograft dysfunction is clinically relevant (4), but a consistent pitfall in BKV-related studies is that this approach does not provide an accurate view of the whole spectrum of BKV replication. Our study confirms that urine and blood viral loads are correlated with each other, as previously described (17) and most importantly, with uCXCL10. Here, our systematic approach demonstrates for the first time two key points: isolated viruria does not increase uCXCL10, and BKV-DNAemia increases uCXCL10 similarly whether or not BKVN is diagnosed in the concurrent biopsy.…”

Section: A B D Csupporting

confidence: 91%

“…Similarly, the median BKV-DNAemia was higher in the BKVN group than in the BKV-DNAemia group (3.96 vs 2.68 Log 10 copies/ml, P < 0.001) and also correlated with uCXCL10/cr to a lesser extent (P < 0.05, Pearson r = 0.28, Figure 2B, right Panel). As previously reported (17), BKV loads in the urine and blood were correlated (P < 0.01, Supplemental Figure 1A).…”

Section: Urine Levels Of Cxcl10 Are Significantly Correlated With Urisupporting

confidence: 86%

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Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation

et al. 2020

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BK virus (BKV) replication increases urinary chemokine C-X-C motif ligand 10 (uCXCL10) levels in kidney transplant recipients (KTRs). Here, we investigated uCXCL10 levels across different stages of BKV replication as a prognostic and predictive marker for functional decline in KTRs after BKV-DNAemia. uCXCL10 was assessed in a cross-sectional study (474 paired urine/blood/biopsy samples and a longitudinal study (1,184 samples from 60 KTRs with BKV-DNAemia). uCXCL10 levels gradually increased with urine (P-value < 0.0001) and blood BKV viral load (P < 0.05) but were similar in the viruria and no BKV groups (P > 0.99). In viremic patients, uCXCL10 at biopsy was associated with graft functional decline [HR = 1.65, 95% CI (1.08–2.51), P = 0.02], irrespective of baseline eGFR, blood viral load, or BKVN diagnosis. uCXL10/cr (threshold: 12.86 ng/mmol) discriminated patients with a low risk of graft function decline from high-risk patients (P = 0.01). In the longitudinal study, the uCXCL10 and BKV-DNAemia trajectories were superimposable. Stratification using the same uCXCL10/cr threshold at first viremia predicted the subsequent inflammatory response, assessed by time-adjusted uCXCL10/cr AUC (P < 0.001), and graft functional decline (P = 0.03). In KTRs, uCXCL10 increases in BKV-DNAemia but not in isolated viruria. uCXCL10/cr is a prognostic biomarker of eGFR decrease, and a 12.86 ng/ml threshold predicts higher inflammatory burdens and poor renal outcomes.

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Section: A B D Csupporting

confidence: 91%

Section: Urine Levels Of Cxcl10 Are Significantly Correlated With Urisupporting

confidence: 86%

Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation

et al. 2020

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“…Plasma qPCR has a higher specificity and negative predictive value, 97.4% and 54.5%, respectively, as compared to urine qPCR values of 91.7% and 27.3%, respectively 17 . Urine BK of >10 7 copies/ml and plasma BK of >10 4 copies/ml have been suggested as a surrogate marker of BKVN, but a positive immunohistochemistry for SV40T of kidney biopsy remains the gold standard test for diagnosis of BKVN 14,18 . Most adult and pediatric studies report the use of both urine and plasma qPCR for diagnosis and monitoring of BK infection 10,19 .…”

Section: Introductionmentioning

confidence: 99%

“…17 Urine BK of >10 7 copies/ml and plasma BK of >10 4 copies/ml have been suggested as a surrogate marker of BKVN, but a positive immunohistochemistry for SV40T of kidney biopsy remains the gold standard test for diagnosis of BKVN. 14,18 Most adult and pediatric studies report the use of both urine and plasma qPCR for diagnosis and monitoring of BK infection. 10,19 Recently, routine screening of all kidney transplant recipients with plasma BK qPCR for the initial 2 years post-transplant has been recommended by the American Society of Transplantation Infectious Diseases Community.…”

Section: Introductionmentioning

confidence: 99%

Treatment of BK virus with a stepwise immunosuppression reduction and intravenous immunoglobulin in pediatric kidney transplant

Mohammad

Kim

Baracco

et al. 2022

Pediatric Transplantation

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Background: BKV and BKVN are common in pediatric kidney transplant, but there is limited data on treatment approaches. Our objective was to study the prevalence of BKV and BKVN utilizing only plasma qPCR and report treatment outcomes with stepwise IR and IVIG.Methods: A retrospective study of all pediatric kidney transplants from 2013 to 2020.Excluded patients >21 years at transplant and immediate graft failure. Surveillance was conducted using only plasma BK qPCR at 1, 3, 6, 9, 12, 18, and 24 months and annually. BKV defined as ≥250 copies/ml and resolution as <250 copies/ml. Presumed BKVN as >10 000 copies/ml despite IR; and BKVN if confirmed on histology.Results: Fifty-six patients were included in the study; 20 (35.7%) had BKV. BKV was associated with longer duration of stent, 40 vs. 33.5 days (p = .004). Two patients (3.5%) had confirmed, and 2(3.5%) had presumed BKVN. The first-line treatment was IR in 100% of patients. BKVN confirmed and presumed received IVIG every month for six doses. Viral resolution was achieved in 70%, and no difference was noted in estimated glomerular filtration rate between BKV and non-BKV group (p = .438). There were no rejection episodes, and graft survival was 100% over median follow-up of 3 years. Conclusions: Plasma qPCR alone is adequate for screening and monitoring treatment of BKV and BKVN. A stepwise IR and IVIG resulted in BKV resolution in the majority of patients. Larger studies are required to study the role of IVIG in the treatment of BKVN.

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“…43 Quantitative BK viral load in plasma: A BK viral load >10,000 copies/ml detected by polymerase chain reaction (PCR) quantification has a good PPV and 93% specificity for PVAN. 26,44,45 Allograft biopsy: Allograft biopsy should be performed when the BK viral load in plasma is >10,000 copies/ml with or without elevated creatinine because of its high association with PVAN. 3,26 Histopathological findings include interstitial inflammation in early infection that progresses to tubular atrophy and interstitial fibrosis.…”

Section: Diagnosismentioning

confidence: 99%

Common Viral Infections In Children After Kidney Transplantation

Chaiyapak

2021

J. Pediatr. Acad.

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Viral infection is a common complication among pediatric kidney transplant recipients, causing significant morbidity and mortality. Sources of viral infection in pediatric transplant recipients include donor allografts, blood products, and latent virus reactivation. Major risks of viral infection include kidney donor-derived, nosocomial and community-acquired infections as well as the immunosuppressive status of recipients. Clinical presentations are variable, ranging from no symptoms to severe disease. Preventive strategies such as immunization and pretransplant-specific viral screening in both donors and recipients are performed before kidney transplantation to identify high-risk recipients. Posttransplant prophylactic strategies include universal prophylaxis and preemptive therapy. Universal antiviral prophylaxis is required for high-risk cytomegalovirus (CMV)-mismatch pediatric recipients. Preemptive therapy requires the administration of sensitive viral surveillance tests to detect subclinical viral infections to optimize individualized immunosuppressive drugs and initiate antiviral therapy. This review summarizes current knowledge regarding common viral infections in children after kidney transplantation, including CMV, BK polyomavirus, Epstein-Barr virus (EBV), and coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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Prediction of BK viremia by urine viral load in renal transplant patients: An analysis of BK viral load results in paired urine and plasma samples

Cited by 15 publications

References 15 publications

Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation

Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation

Treatment of BK virus with a stepwise immunosuppression reduction and intravenous immunoglobulin in pediatric kidney transplant

Common Viral Infections In Children After Kidney Transplantation

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