Polyoma BK Virus in Kidney Transplant Recipients: Screening, Monitoring, and Management

Myint, Thida; Chong, Chanel H.; Wyld, Melanie; Nankivell, Brian J.; Kable, Kathy; Wong, Germaine

doi:10.1097/tp.0000000000003801

Cited by 22 publications

(15 citation statements)

References 202 publications

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“…For instance, BK nephropathy is complicit for up to 80% of kidney transplant failures within 2 years, especially if untimely diagnosed ( Ambalathingal et al., 2017 ). Due to its severe consequences, the timely and accurate detection of BK polyomavirus is critical ( Reploeg et al., 2001 ; Myint et al., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Advantage of precision metagenomics for urinary tract infection diagnostics

Almas¹,

Carpenter

Rowan³

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundUrinary tract infections (UTIs) remain a diagnostic challenge and often promote antibiotic overuse. Despite urine culture being the gold standard for UTI diagnosis, some uropathogens may lead to false-negative or inconclusive results. Although PCR testing is fast and highly sensitive, its diagnostic yield is limited to targeted microorganisms. Metagenomic next-generation sequencing (mNGS) is a hypothesis-free approach with potential of deciphering the urobiome. However, clinically relevant information is often buried in the enormous amount of sequencing data.MethodsPrecision metagenomics (PM) is a hybridization capture-based method with potential of enhanced discovery power and better diagnostic yield without diluting clinically relevant information. We collected 47 urine samples of clinically suspected UTI and in parallel tested each sample by microbial culture, PCR, and PM; then, we comparatively analyzed the results. Next, we phenotypically classified the cumulative microbial population using the Explify® data analysis platform for potential pathogenicity.ResultsResults revealed 100% positive predictive agreement (PPA) with culture results, which identified only 13 different microorganisms, compared to 19 and 62 organisms identified by PCR and PM, respectively. All identified organisms were classified into phenotypic groups (0–3) with increasing pathogenic potential and clinical relevance. This PM can simultaneously quantify and phenotypically classify the organisms readily through bioinformatic platforms like Explify®, essentially providing dissected and quantitative results for timely and accurate empiric UTI treatment.ConclusionPM offers potential for building effective diagnostic models beyond usual care testing in complex UTI diseases. Future studies should assess the impact of PM-guided UTI management on clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Advantage of precision metagenomics for urinary tract infection diagnostics

Almas¹,

Carpenter

Rowan³

et al. 2023

Front. Cell. Infect. Microbiol.

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“…The reactivation of the virus may occur with the use of immunosuppression. Polyomavirus BK virus reactivation in kidney transplant recipients can lead to BK polyoma virus-associated nephropathy (BKPyVAN), which is associated with graft dysfunction in >90% and graft loss in over 50% of the affected individuals [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Risk factors for graft loss and death among kidney transplant recipients: A competing risk analysis

et al. 2022

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Introduction Kidney transplantation is the best therapeutical option for CKD patients. Graft loss risk factors are usually estimated with the cox method. Competing risk analysis could be useful to determine the impact of different events affecting graft survival, the occurrence of an outcome of interest can be precluded by another. We aimed to determine the risk factors for graft loss in the presence of mortality as a competing event. Methods A retrospective cohort of 1454 kidney transplant recipients who were transplanted between July 1, 2008, to May 31, 2019, in Colombiana de Trasplantes, were analyzed to determine risk factors of graft loss and mortality at 5 years post-transplantation. Kidney and patient survival probabilities were estimated by the competing risk analysis. The Fine and Gray method was used to fit a multivariable model for each outcome. Three variable selection methods were compared, and the bootstrapping technique was used for internal validation as split method for resample. The performance of the final model was assessed calculating the prediction error, brier score, c-index and calibration plot. Results Graft loss occurred in 169 patients (11.6%) and death in 137 (9.4%). Cumulative incidence for graft loss and death was 15.8% and 13.8% respectively. In a multivariable analysis, we found that BKV nephropathy, serum creatinine and increased number of renal biopsies were significant risk factors for graft loss. On the other hand, recipient age, acute cellular rejection, CMV disease were risk factors for death, and recipients with living donor had better survival compared to deceased-donor transplant and coronary stent. The c-index were 0.6 and 0.72 for graft loss and death model respectively. Conclusion We developed two prediction models for graft loss and death 5 years post-transplantation by a unique transplant program in Colombia. Using a competing risk multivariable analysis, we were able to identify 3 significant risk factors for graft loss and 5 significant risk factors for death. This contributes to have a better understanding of risk factors for graft loss in a Latin-American population. The predictive performance of the models was mild.

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“…31 Patients with risk factors such as use of T cell–depleting agents as induction therapy, prior acute rejection episodes, and human antigen leukocyte incompatibility may benefit from more frequent screening to increase the probability of detecting viremia early. 32 In this model, we did not assess whether these additional risk factors combined with screening frequency influence cost-effectiveness. The present analysis also assumed that immunosuppression reduction strategies, cessation of antimetabolites, and the use of adjuvant therapies such as intravenous immunoglobulins are effective management strategies for BKPyV-DNAemia and PyVAN.…”

Section: Discussionmentioning

confidence: 99%

Economic Evaluation of Screening for Polyomavirus Infection in Kidney Transplant Recipients: A Cost-Utility Analysis

Wong

Myint

Lee

et al. 2022

Transplantation Direct

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Background: Screening for polyomavirus infection after kidney transplantation is recommended by clinical practice guidelines, but cost-effectiveness of this strategy is uncertain. The aim of this study was to estimate the incremental costs and benefits of routine screening for polyomavirus infection compared with no screening in kidney transplant recipients. Methods: Probabilistic Markov models were constructed to compare the health and economic benefits of routine screening for polyomavirus infection using real-time polymerase chain reaction assay. A series of 1-way and probabilistic sensitivity analyses were conducted to define the most influential variables in the model. Results: Monthly screening for 6 mo followed by 3 monthly screenings until 12 mo after transplant was dominant (lower costs and improved outcomes). Compared with no screening, the incremental benefits of screening were 0.294 life-years saved and 0.232 quality-adjusted life-years saved. Total savings from screening were $6986 Australian dollars ($5057 US dollars). The cost-effectiveness ratios were most sensitive to the costs of transplantation and dialysis, age of transplantation, prevalence of viremia, and probability of death in patients with a history of polyomavirus-associated nephropathy. Probabilistic sensitivity analysis indicated that screening (compared with no screening) was the dominant strategy across all plausible ranges of transition probabilities. Conclusions: Screening for polyomavirus infections 1 year following transplantation appears to save money, improves survival, and improves quality of life in kidney transplant recipients.

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Polyoma BK Virus in Kidney Transplant Recipients: Screening, Monitoring, and Management

Cited by 22 publications

References 202 publications

Advantage of precision metagenomics for urinary tract infection diagnostics

Advantage of precision metagenomics for urinary tract infection diagnostics

Risk factors for graft loss and death among kidney transplant recipients: A competing risk analysis

Economic Evaluation of Screening for Polyomavirus Infection in Kidney Transplant Recipients: A Cost-Utility Analysis

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