Incidence and risk factors of kidney allograft loss due to BK nephropathy in the pediatric population: A retrospective analysis of the UNOS/OPTN database

Patel, Hemant; Rodig, Nancy; Agrawal, Nikhil; Cardarelli, Francesca

doi:10.1111/petr.13927

Cited by 10 publications

(15 citation statements)

References 20 publications

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“…66 In consequence of the kidney damage, BKVN increases the risk of allograft loss in both adult and pediatric kidney recipients (Table 1). 120,121 Higher BKV viral load and donor BKV infection have been associated with an increased risk of BVKN in kidney recipients. 122,123 BKVN occurs predominantly in the context of kidney transplantation.…”

Section: Bk Virusmentioning

confidence: 99%

Infection, Rejection, and the Connection

Higdon

Tan

2022

Transplantation

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Solid organ transplantation is a life-saving treatment for people with end-stage organ disease. Immune-mediated transplant rejection is a common complication that decreases allograft survival. Although immunosuppression is required to prevent rejection, it also increases the risk of infection. Some infections, such as cytomegalovirus and BK virus, can promote inflammatory gene expression that can further tip the balance toward rejection. BK virus and other infections can induce damage that resembles the clinical pathology of rejection, and this complicates accurate diagnosis. Moreover, T cells specific for viral infection can lead to rejection through heterologous immunity to donor antigen directly mediated by antiviral cells. Thus, viral infections and allograft rejection interact in multiple ways that are important to maintain immunologic homeostasis in solid organ transplant recipients. Better insight into this dynamic interplay will help promote long-term transplant survival.

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Section: Bk Virusmentioning

confidence: 99%

Infection, Rejection, and the Connection

Higdon

Tan

2022

Transplantation

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“…BK virus (BKV) is a common childhood virus with an immunoglobulin G (IgG) seroprevalence exceeding 90% among all children aged 5–20 years 1,2 . Following a primary infection in the human host, BKV subsequently remains latent within the renal tubular cells and uroepithelium 1,2 .…”

Section: Introductionmentioning

confidence: 99%

“…Particularly in the case of kidney transplantation, reactivated BKV may shed in the urine (BK viruria) and has the potential to result in both BK viremia and BKV‐associated nephropathy (BKVN), putting kidney transplant recipients (KTRs) at risk for poor graft outcomes. Significant morbidity is associated with BKVN in pediatric KTRs, with studies quoting incidences of greater than 50% for allograft dysfunction and up to 9% for renal allograft loss 2–4 …”

Section: Introductionmentioning

confidence: 99%

Leflunomide as adjunct therapy for BK viremia management in pediatric kidney transplant recipients

Aldieri,

Chandran,

Matossian

et al. 2024

Pediatric Transplantation

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BackgroundBK viremia after kidney transplantation (KT) poses significant risk for BK virus‐associated nephropathy and impacts graft survival. Conventional treatment involves reduction of immunosuppression, which in turn may increase risk for rejection. To address this dilemma, use of anti‐viral therapy with immunosuppressive properties such as leflunomide is an attractive option.MethodsWe performed a multi‐center, retrospective chart review to report tolerability and effectiveness of leflunomide use for the eradication of BK viremia and prevention of BK virus‐associated nephropathy in pediatric KT recipients.ResultsSeventy patients prescribed leflunomide were included and were followed up from initiation until 1 year following leflunomide completion. BK viremia was eradicated in 64 (91.4%) patients including 8 of 11 with nephropathy (BKVN) on initial biopsy. Reduced anti‐proliferative medication (AP) dosing was not associated with increase in biopsy proven rejection (BPAR). However, complete discontinuation of AP during leflunomide therapy was associated with increase in BPAR in uni‐ and multivariate logistic regression, as was targeted reduction in calcineurin inhibitor (CNI) trough goals. One graft was lost to BKVN. There was no significant association found between time to BK eradication and leflunomide trough concentration, mycophenolate dose reduction, or steroid use (univariate logistic regression). Few leflunomide adverse drug reactions (ADR) were reported (most commonly: gastrointestinal, hematologic).ConclusionLeflunomide is a promising adjunctive treatment to immunosuppression reduction for BK virus eradication with minimal ADR. AP reduction, not discontinuation, and judicious reduction in CNI trough goals with close monitoring, is a promising strategy for treatment of BK viremia with concomitant use of leflunomide therapy.

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“…This has been achieved mostly through a dramatic decrease in acute rejection rates 1,2 . However, infection remains a major cause of morbidity and mortality in these patients 3–5 . According to reports of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS), infections have replaced rejection as the leading cause of hospitalization in this population 1 …”

Section: Introductionmentioning

confidence: 99%

“…1,2 However, infection remains a major cause of morbidity and mortality in these patients. [3][4][5] According to reports of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS), infections have replaced rejection as the leading cause of hospitalization in this population. 1 Viral infections, specifically cytomegalovirus (CMV), Epstein-Barr virus (EBV), and polyoma BK virus (BKV), present significant risks to patients following kidney transplantation.…”

Section: Introductionmentioning

confidence: 99%

EBV, CMV, and BK viral infections in pediatric kidney transplantation: Frequency, risk factors, treatment, and outcomes

Levi

Davidovits

Alfandari

et al. 2021

Pediatric Transplantation

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Background Improved short‐ and long‐term outcomes of kidney transplantation have been achieved over the past decades due to improved immunosuppression. This may have increased the risk for infections and, particularly, for the viral infections: cytomegalovirus (CMV), Epstein‐Barr virus (EBV), and polyoma BK virus (BKV). Methods A retrospective review of viremic CMV, EBV, and BKV infections in pediatric renal transplant recipients treated and followed by a national referral center over a 10‐year period. Results Sixty‐seven patients (68% males) received 68 kidney grafts (62% from living donors) during the study period; the mean follow‐up period was 5.2 ± 2.4 years. Twenty‐seven viremic episodes were documented (CMV: 13, EBV: 6, BKV: 8) in 24 patients (35.2%). The median time (interquartile range) to viremia post‐transplant was 11 (4–38) months. The viral infection rate was significantly higher in the years 2014–2015 than in previous years (61% vs. 29%, p = .017). Compared to patients who did not develop viremia, patients with viremias were younger at the time of transplantation, were more likely to receive thymoglobulin induction pre‐transplant and to develop an acute rejection. Multiple logistic regression modeling identified transplant year and recipient's age as significant risk factors for viremia. Graft outcome and eGFR at the last follow‐up was similar between patients who did and did not develop viremia. Conclusions Viral infections continue to be a major cause of morbidity in pediatric kidney transplant recipients. However, with close monitoring and prompt intervention, patient and renal outcomes remain favorable.

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Incidence and risk factors of kidney allograft loss due to BK nephropathy in the pediatric population: A retrospective analysis of the UNOS/OPTN database

Cited by 10 publications

References 20 publications

Infection, Rejection, and the Connection

Infection, Rejection, and the Connection

Leflunomide as adjunct therapy for BK viremia management in pediatric kidney transplant recipients

EBV, CMV, and BK viral infections in pediatric kidney transplantation: Frequency, risk factors, treatment, and outcomes

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