BK Nephropathy in the Modern Era: What Have We Learned?

BK polyomavirus (BKPyV) remains a significant cause of graft dysfunction and failure in kidney transplant recipients, with DNAemia affecting up to 30% and nephropathy contributing to approximately 7% of graft losses. This review synthesizes current understanding of BKPyV pathogenesis, risk factors, and management strategies. Screening protocols and immunosuppression reduction remain the cornerstone of care, though emerging therapies-including monoclonal antibodies and virus-specific T-cell therapies-offer promise.

dd-cfDNA Significantly Improves Rejection Yield in Kidney Transplant Biopsies.

Donor-derived cell-free DNA (dd-cfDNA) is a biomarker that enables the early detection of immune-mediated graft injury. This study evaluated the clinical utility of dd-cfDNA in predicting the presence of biopsy-proven rejection (BPAR). We analyzed 1,070 biopsies from 1,743 kidney transplant recipients enrolled in the prospective, multicenter Kidney Allograft Outcomes AlloSure Registry (KOAR).

Inflammation among kidney transplant donors with and without HIV: Multicenter HOPE in Action Consortium.

Kidney transplantation from donors with HIV has recently become standard clinical practice, but the plasma inflammatory profile is not well characterized. Thirty-two cytokines and chemokines were evaluated among donors with HIV (n = 63) and without HIV (n = 41). Wilcoxon rank sum test was used to compare cytokines between groups.

A systematic literature review and meta-analysis evaluated modifiable risk factors for the development of BK polyoma virus-associated complications.

Background: BK polyomavirus-associated nephropathy (BKPyVAN) remains a significant cause of kidney graft injury. Several risk factors are suggested, mostly based on monocentric or retrospective studies. By performing a systematic literature review and comprehensive meta-analysis we sought to provide solid assumptions and test the reproducibility of known modifiable clinical risk factors for BKPyV.

Being Waitlisted is not Enough-Identification of Pseudo-access to Kidney Transplantation in the United States.

Objective: We sought to determine how kidney transplant center volume impacts waitlisted candidate access to transplant.

Summary Background Data: Over 90,000 candidates await a kidney transplant, of which we hypothesized that waitlist access is subject to significant program-level variation, potentially resulting in pseudo-access: a state where the waitlisted candidate does not achieve expected transplantation.

Methods: Center-level data on all U.

Kaposi Sarcoma-Associated Herpesvirus Risk and Disease in Kidney Donors and Transplant Recipients with HIV in the United States.

Background: Due to high prevalence of Kaposi Sarcoma (KS)-Associated Herpesvirus (KSHV) among people with HIV, KSHV-associated disease (KAD) may be increased after kidney transplantation from donors with HIV (HIV D+) to recipients with HIV (HIV R+).

Methods: Anti-KSHV antibodies were measured in HIV R+ and donors with and without HIV (HIV D-) using a 30-antigen multiplex assay within three multicenter kidney transplantation studies. KSHV seropositivity was defined as reactivity to conventional KSHV antigens (≥1 ORF73 or K8.

genotype and patient outcomes in US and South African transplant recipients with HIV who received kidneys from donors with HIV.

Importance: Lower kidney allograft survival has been demonstrated in kidney transplant recipients (KTR) without HIV whose donors have two apolipoprotein L1 () renal risk variants (RRV). The effects of RRV on kidney transplant outcomes in people with HIV (PWH) have not been fully assessed.

Objective: To determine whether renal risk variants (G1/G2) in donors or recipients are associated with outcomes of kidney transplantation in people with HIV (PWH)?

Design: Comparative analysis of kidney allograft outcomes in two of the largest longitudinal clinical studies examining transplantation outcomes in PWH.

Phase 2, Randomized, Double-blind, Placebo-controlled Study of Fiztasovimab (NPC-21) for Kidney Transplant Recipients at High Risk of Cytomegalovirus Infection (LionHeart21).

Background: Kidney transplantation (KT) has dramatically improved the quality of life of patients with end-stage kidney disease. However, the incidence of opportunistic infections has also increased because of immunosuppression. A common infection after KT is cytomegalovirus (CMV).

Long-term Safety in Epstein-Barr Virus-Seropositive Kidney-only Transplant Recipients Treated With Belatacept in Clinical Practice: Final Study Results From the ENLiST Registry.

Background: Belatacept, a selective T-cell costimulation blocker, was associated with improved survival and renal function but also with a risk of posttransplant lymphoproliferative disorder (PTLD) in adult kidney transplant recipients in phase 3 trials. This registry examined long-term safety in Epstein-Barr virus (EBV)-seropositive kidney transplant recipients treated with belatacept.

Methods: This US-based, prospective, voluntary, multicenter registry (Evaluating Nulojix Long-Term Safety in Transplant [ENLiST]) included adult EBV-seropositive kidney-only transplant recipients treated de novo (within 14 d of transplantation) with belatacept.

A Contemporary Analysis of Mental Well-being Among Living Donor Kidney Applicants.

Background: Living donation is paramount for expanding the donor pool. The aim of this study was to assess changes over time in self-reported mental health of living donor kidney applicants in efforts to inform patient-centered discussions with potential donors.

Methods: Kidney donor applications from 2017 through 2021 were compiled.

The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation.

BK polyomavirus (BKPyV) remains a significant challenge after kidney transplantation. International experts reviewed current evidence and updated recommendations according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Risk factors for BKPyV-DNAemia and biopsy-proven BKPyV-nephropathy include recipient older age, male sex, donor BKPyV-viruria, BKPyV-seropositive donor/-seronegative recipient, tacrolimus, acute rejection, and higher steroid exposure.

Posoleucel in Kidney Transplant Recipients with BK Viremia: Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

Key Points: Posoleucel was generally safe, well tolerated, and associated with a greater reduction of BK viremia compared with placebo. BK viremia reduction occurred coincident with an increase in the circulating frequency of BK virus–specific T cells in posoleucel recipients. The presence and persistence of posoleucel was confirmed by T-cell receptor variable sequencing.

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.

Background: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population.

Methods: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022.

HIV-Positive Liver Transplant Does not Alter the Latent Viral Reservoir in Recipients With Antiretroviral Therapy-Suppressed HIV.

The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10).

An Unusual Presentation of Metastatic BK Virus-Associated Urothelial Carcinoma Arising in the Allograft, Persisting After Transplant Nephrectomy.

We report a 32-year-old male 14 years post-living-related kidney transplant presenting with new-onset hematuria and BK viremia. He was found to have BK virus-associated urothelial carcinoma originating in the renal allograft with locally advanced disease and metastases to multiple sites. He also developed acute T-cell-mediated rejection in the setting of immunosuppression reduction for BK viremia prior to undergoing transplant nephrectomy.

Short-term kidney transplant outcomes from severe acute respiratory syndrome coronavirus 2 lower respiratory tract positive donors.

Objective: In this study, we aim to assess short-term allograft outcomes following deceased donor kidney transplantation from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lower respiratory tract (LRT) nucleic acid testing (NAT) positive donors.

Methods: From September to December 2021, SARS-CoV-2 NAT positive organ donors, whose solid abdominal organs were transplanted at our academic medical center were identified. Donors were stratified into having tested positive for SARS-CoV-2 in an upper respiratory tract (URT) or LRT sample.

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT.

Association of Inflammatory Biomarkers with Immunosuppression Management and Outcomes in Kidney Transplant Recipients with COVID-19.

Background: Kidney transplant recipients with coronavirus disease 2019 (COVID-19) are at increased risk for adverse outcomes, such as acute kidney injury (AKI), intensive care unit (ICU) admission, and death. The association of inflammatory biomarkers with outcomes and the impact of changes in immunosuppression on biomarker levels are unknown.

Methods: We investigated factors associated with a composite of AKI, ICU admission, or death, and whether immunosuppression changes correlated with changes in inflammatory biomarkers and outcomes in kidney transplant recipients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction.

Clinical Rationale for a Routine Testing Schedule Using Donor-Derived Cell-Free DNA After Kidney Transplantation.

Kidney transplant recipients require meticulous clinical and laboratory surveillance to monitor allograft health. Conventional biomarkers, including serum creatinine and proteinuria, are lagging indicators of allograft injury, often rising only after significant and potentially irreversible damage has occurred. Immunosuppressive medication levels can be followed, but their utility is largely limited to guiding dosing changes or assessing adherence.

Assessing accuracy of estimated dry weight in dialysis patients post transplantation: the kidney knows best.

Introduction: Estimated dry weight is used to guide fluid removal during outpatient hemodialysis sessions. Errors in estimated dry weight can result in intradialytic hypotension and interdialytic fluid overload. The goal of this study was to assess the accuracy of estimated dry weight by comparing it to the 2-week post-transplant weight in two cohorts of hemodialysis patients.

Long-Term Immunosuppression Management: Opportunities and Uncertainties.

The long-term management of maintenance immunosuppression in kidney transplant recipients remains complex. The vast majority of patients are treated with the calcineurin inhibitor tacrolimus as the primary agent in combination with mycophenolate, with or without corticosteroids. A tacrolimus trough target 5-8 ng/ml seems to be optimal for rejection prophylaxis, but long-term tacrolimus-related side effects and nephrotoxicity support the ongoing evaluation of noncalcineurin inhibitor-based regimens.

Optimization of de novo belatacept-based immunosuppression administered to renal transplant recipients.

Kidney transplant recipients administered belatacept-based maintenance immunosuppression present with a more favorable metabolic profile, reduced incidence of de novo donor-specific antibodies (DSAs), and improved renal function and long-term patient/graft survival relative to individuals receiving calcineurin inhibitor (CNI)-based immunosuppression. However, the rates and severity of acute rejection (AR) are greater with the approved belatacept-based regimen than with CNI-based immunosuppression. Although these early co-stimulation blockade-resistant rejections are typically steroid sensitive, the higher rate of cellular AR has led many transplant centers to adopt immunosuppressive regimens that differ from the approved label.