scholarly journals Clinical Relevance of Absolute BK Polyoma Viral Load Kinetics in Patients With Biopsy Proven BK Polyomavirus Associated Nephropathy

2022 ◽  
Vol 8 ◽  
Author(s):  
Haris Omić ◽  
Johannes Phillip Kläger ◽  
Harald Herkner ◽  
Stephan W. Aberle ◽  
Heinz Regele ◽  
...  

Introduction: The absolute BK viral load is an important diagnostic surrogate for BK polyomavirus associated nephropathy (PyVAN) after renal transplant (KTX) and serial assessment of BK viremia is recommended. However, there is no data indicating which particular viral load change, i.e., absolute vs. relative viral load changes (copies/ml; percentage of the preceding viremia) is associated with worse renal graft outcomes.Materials and Methods: In this retrospective study of 91 biopsy proven PyVAN, we analyzed the interplay of exposure time, absolute and relative viral load kinetics, baseline risk, and treatment strategies as risk factors for graft loss after 2 years using a multivariable Poisson-model.Results: We compared two major treatment strategies: standardized immunosuppression (IS) reduction (n = 53) and leflunomide (n = 30). The median viral load at the index biopsy was 2.15E+04 copies/ml (interquartile range [IQR] 1.70E+03–1.77E+05) and median peak viremia was 3.6E+04 copies/ml (IQR 2.7E+03–3.3E+05). Treatment strategies and IS-levels were not related to graft loss. After correction for baseline viral load and estimated glomerular filtration rate (eGFR), absolute viral load decrease/unit remained an independent risk factor for graft loss [incidence rate ratios [IRR] = 0.77, (95% CI 0.61–0.96), p = 0.02].Conclusion: This study provides evidence for the prognostic importance of absolute BK viremia kinetics as a dynamic parameter indicating short-term graft survival independently of other established risk factors.

2006 ◽  
Vol 6 ◽  
pp. 412-528 ◽  
Author(s):  
Christine Wu ◽  
Parmjeet Randhawa ◽  
Jerry McCauley

BK virus is ubiquitously present in the latent state in humans, and awareness of the importance of BK polyomavirus is emerging among the kidney transplant community. First discovered in 1971 in the urine of a renal transplant recipient, BK virus nephropathy (BKVN) has come to be recognized as a significant cause of genitourinary disease and potential graft loss in the kidney transplant patient. In this review, we discuss the risk factors, available methods of diagnosis and therapeutic monitoring, and current approaches to therapy of BKVN.


2013 ◽  
Vol 94 (6) ◽  
pp. 1259-1265 ◽  
Author(s):  
Cristina Bucci ◽  
Annette von Delft ◽  
Annabel Christian ◽  
Vicki M. Flemming ◽  
Abby Harrison ◽  
...  

IL28B host genetic make-up is known to play a critical role in the outcome of genotype 1 hepatitis C virus (HCV) infection in the context of both primary infection and therapy. However, the role of IL28B in subtype 3a infection remains unclear, and has not yet been assessed in the UK population where subtype 3a is dominant. In this study, we evaluated the role of the IL28B single-nucleotide polymorphism rs8099917 in 201 patients recruited from two well-defined cohorts (from Nottingham and Oxford), treated with the standard-of-care therapy of pegylated interferon and ribavirin for 24 weeks. We showed that the ‘favourable’ IL28B gene was associated with a rapid virological response to therapy at 4 weeks (P<0.0001), but not with a sustained virological response to therapy. The median viral load at baseline, before therapy, was markedly increased in people with the ‘favourable’ IL28B genotype [median viral load for the TT allele, 925 961 IU ml−1 (range 2200–21 116 965 IU ml−1), and for the GT or GG allele, 260 284 IU ml−1 (range 740–7 560 000 IU ml−1); P = 0.0010]. Our results suggest that the host genetic response plays an important role in early viral clearance of subtype 3a virus from the blood. However, significant reservoirs of infection must persist, as viral relapse is common, even in those with the favourable host genotype.


2020 ◽  
Author(s):  
Chloe A Teasdale ◽  
Cecilia Hernandez ◽  
Allison Zerbe ◽  
Duncan Chege ◽  
Mark Hawken ◽  
...  

Abstract Background: Increased coagulation biomarkers are associated with poor outcomes among people living with HIV(PLHIV). There are few data available from African cohorts demonstrating the effect of antiretroviral therapy (ART) on coagulation biomarkers. Methods: From March 2014 to October 2014, ART-naïve PLHIV initiating non-nucleoside reverse transcriptase inhibitor-based ART were recruited from seven clinics in western Kenya and followed for up to 12 months. Demographics, clinical history and blood specimens were collected. Logistic regression models adjusted for intrasite clustering examined associations between viral load and D-Dimer at baseline. Mixed linear effects models were used to estimate mean change from baseline to six months overall, and by baseline viral load, sex and TB status at enrollment. Mean change in D-dimer at six months is reported on the log10 scale and as percentage change from baseline. Results: Among 611 PLHIV enrolled, 66% were female, median age was 34 years (interquartile range (IQR) 29-43 years), 31 (5%) participants had tuberculosis and median viral load was 113,500 copies/mL (IQR: 23,600-399,000). At baseline, 311 (50.9%) PLHIV had elevated D-dimer (>500 ng/mL) and median D-dimer was 516.4 ng/mL (IQR: 302.7-926.6) (log baseline D-dimer: 2.7, IQR: 2.5-3.0). Higher baseline D-dimer was significantly associated with higher viral load (p<0.0001), female sex (p=0.02) and tuberculosis (p=-0.02). After six months on ART, 518 (84.8%) PLHIV had achieved viral load <1,000 copies/mL and median D-dimer was 390.0 (IQR: 236.6-656.9) (log D-dimer: 2.6, IQR: 2.4-2.8). Mean change in log D-dimer from baseline to six months was -0.12 (95%CI -0.15, - 0.09) (p<0.0001) indicating at 31.3% decline (95%CI -40.0, -23.0) in D-dimer levels over the first six months on ART. D-dimer decline after ART initiation was significantly greater among PLHIV with tuberculosis at treatment initiation (-172.1%, 95%CI -259.0, -106.3; p<0.0001) and those with log viral load >6.0 copies/mL (-91.1%, 95%CI -136.7, -54.2; p<0.01). Conclusions: In this large Kenyan cohort of PLHIV, women, those with tuberculosis and higher viral load had elevated baseline D-dimer. ART initiation and viral load suppression among ART-naïve PLHIV in Kenya were associated with significant decrease in D-dimer at six months in this large African cohort.


2019 ◽  
Vol 74 (4) ◽  
pp. 331-338 ◽  
Author(s):  
Min Zhang ◽  
Yong Han ◽  
Yonghua Yuan ◽  
Jie Cai ◽  
Jing Zhang ◽  
...  

Background: New-onset diabetes after transplantation ­(NODAT) is a frequent complication after heart transplantation (HT) and is associated with graft loss and patient survival. Objectives: The aim of this study was to identify the incidence and associated factors contributing to NODAT in Chinese heart transplant recipients. Methods: Adult patients without diabetes mellitus before HT were enrolled in this study. NODAT was diagnosed according to the criteria recommended by the American Diabetes Association. The cumulative incidence was determined at 3, 6, and 12 months, respectively. The risk factors of NODAT were estimated by logistic regression analysis. Results: A total of 154 adults who first received HT were included. Among them, 50 (32.5%) recipients were diagnosed with NODAT after a median follow-up time of 611 days. The cumulative incidence of NODAT was 27.3% at 3 months, 29.9% at 6 months, and 30.5% at 12 months, respectively. Independent risk factors for NODAT included age ≥45 years (OR 3.82, 95% CI 1.57–9.31; p = 0.003), hypertension (OR 3.28, 95% CI 1.17–9.20; p= 0.024), and transient hyperglycemia (OR 12.13, 95% CI 3.35–43.92; p < 0.001). Moreover, recipients treated with both acarbose and insulin for transient hyperglycemia had a significantly higher prevalence of NODAT than those without any anti-diabetic agents (OR 5.35, 95% CI 1.21–23.64; p = 0.027). Conclusions: Age ≥45 years, hypertension, transient hyperglycemia, and associated treatment strategies are imperative to identify recipients at high risk of developing ­NODAT.


2020 ◽  
Author(s):  
Chloe A Teasdale ◽  
Cecilia Hernandez ◽  
Allison Zerbe ◽  
Duncan Chege ◽  
Mark Hawken ◽  
...  

Abstract Background: Increased coagulation biomarkers are associated with poor outcomes among people living with HIV(PLHIV). There are few data available from African cohorts demonstrating the effect of antiretroviral therapy (ART) on coagulation biomarkers.Methods: From March 2014 to October 2014, ART-naïve PLHIV initiating non-nucleoside reverse transcriptase inhibitor-based ART were recruited from seven clinics in western Kenya and followed for up to 12 months. Demographics, clinical history and blood specimens were collected. Logistic regression models adjusted for intrasite clustering examined associations between HIV viral load and D-Dimer at baseline. Mixed linear effects models were used to estimate mean change from baseline to six months overall, and by baseline viral load, sex and TB status at enrollment. Mean change in D-dimer at six months is reported on the log10 scale and as percentage change from baseline.Results: Among 611 PLHIV enrolled, 66% were female, median age was 34 years (interquartile range (IQR) 29-43 years), 31 (5%) participants had tuberculosis and median viral load was 113,500 copies/mL (IQR: 23,600-399,000). At baseline, 311 (50.9%) PLHIV had elevated D-dimer (>500 ng/mL) and median D-dimer was 516.4 ng/mL (IQR: 302.7-926.6) (log baseline D-dimer: 2.7, IQR: 2.5-3.0). Higher baseline D-dimer was significantly associated with higher viral load (p<0.0001), female sex (p=0.02) and tuberculosis (p=-0.02). After six months on ART, 518 (84.8%) PLHIV had achieved viral load <1,000 copies/mL and median D-dimer was 390.0 (IQR: 236.6-656.9) (log D-dimer: 2.6, IQR: 2.4-2.8). Mean change in log D-dimer from baseline to six months was -0.12 (95%CI -0.15, - 0.09) (p<0.0001) indicating at 31.3% decline (95%CI -40.0, -23.0) in D-dimer levels over the first six months on ART. D-dimer decline after ART initiation was significantly greater among PLHIV with tuberculosis at treatment initiation (-172.1%, 95%CI -259.0, -106.3; p<0.0001) and those with log viral load >6.0 copies/mL (-91.1%, 95%CI -136.7, -54.2; p<0.01). Conclusions: In this large Kenyan cohort of PLHIV, women, those with tuberculosis and higher viral load had elevated baseline D-dimer. ART initiation and viral load suppression among ART-naïve PLHIV in Kenya were associated with significant decrease in D-dimer at six months in this large African cohort.


2020 ◽  
Author(s):  
Chloe A Teasdale ◽  
Cecilia Hernandez ◽  
Allison Zerbe ◽  
Duncan Chege ◽  
Mark Hawken ◽  
...  

Abstract Background Increased coagulation biomarkers are associated with poor outcomes among people living with HIV(PLHIV). There are few data available from African cohorts demonstrating the effect of antiretroviral therapy (ART) on coagulation biomarkers. Methods From March 2014 to October 2014, ART-naïve PLHIV initiating non-nucleoside reverse transcriptase inhibitor-based ART were recruited from seven clinics in western Kenya and followed for up to 12 months. Demographics, clinical history and blood specimens were collected. Logistic regression models adjusted for intrasite clustering examined associations between viral load and D-Dimer at baseline. Mixed linear effects models were used to estimate mean change from baseline to six months overall, and by baseline viral load, sex and TB status at enrollment. Mean change in D-dimer at six months is reported on the log10 scale and as percentage change from baseline. Results Among 611 PLHIV enrolled, 66% were female, median age was 34 years (interquartile range (IQR) 29–43 years), 31 (5%) participants had tuberculosis and median viral load was 113,500 copies/mL (IQR: 23,600 − 399,000). At baseline, 311 (50.9%) PLHIV had elevated D-dimer (> 500 ng/mL) and median D-dimer was 516.4 ng/mL (IQR: 302.7-926.6) (log baseline D-dimer: 2.7, IQR: 2.5-3.0). Higher baseline D-dimer was significantly associated with higher viral load (p < 0.0001), female sex (p = 0.02) and tuberculosis (p=-0.02). After six months on ART, 518 (84.8%) PLHIV had achieved viral load < 1,000 copies/mL and median D-dimer was 390.0 (IQR: 236.6-656.9) (log D-dimer: 2.6, IQR: 2.4–2.8). Mean change in log D-dimer from baseline to six months was − 0.12 (95%CI -0.15, − 0.09) (p < 0.0001) indicating at 31.3% decline (95%CI -40.0, -23.0) in D-dimer levels over the first six months on ART. D-dimer decline after ART initiation was significantly greater among PLHIV with tuberculosis at treatment initiation


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 351
Author(s):  
Baptiste Demey ◽  
Véronique Descamps ◽  
Claire Presne ◽  
Francois Helle ◽  
Catherine Francois ◽  
...  

Background: Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. Methods: In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Results: Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. Conclusions: After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen.


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