scholarly journals BK Polyomavirus Micro-RNAs: Time Course and Clinical Relevance in Kidney Transplant Recipients

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 351
Author(s):  
Baptiste Demey ◽  
Véronique Descamps ◽  
Claire Presne ◽  
Francois Helle ◽  
Catherine Francois ◽  
...  
Keyword(s):  
Viral Replication ◽  
Kidney Transplant ◽  
Clinical Relevance ◽  
Graft Loss ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Bk Polyomavirus ◽  
Micro Rnas

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.

Stabilization of renal function after the first year of follow-up in kidney transplant recipients treated for significant BK polyomavirus infection or BK polyomavirus-associated nephropathy

2017 ◽  
Vol 19 (3) ◽  
pp. e12681 ◽  
Author(s):  
Marie-Christine Simard-Meilleur ◽  
Paule Bodson-Clermont ◽  
Gilles St-Louis ◽  
Michel R. Pâquet ◽  
Catherine Girardin ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Transplant ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Bk Polyomavirus

scholarly journals Non-permissive human conventional CD1c+ dendritic cells enable trans-infection of human primary renal tubular epithelial cells and protect BK polyomavirus from neutralization

2021 ◽  
Vol 17 (2) ◽  
pp. e1009042
Author(s):  
Mathieu Sikorski ◽  
Flora Coulon ◽  
Cécile Peltier ◽  
Cécile Braudeau ◽  
Alexandra Garcia ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Graft Loss ◽  
Endocytic Pathway ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Human Virus ◽  
Bk Polyomavirus

The BK polyomavirus (BKPyV) is a ubiquitous human virus that persists in the renourinary epithelium. Immunosuppression can lead to BKPyV reactivation in the first year post-transplantation in kidney transplant recipients (KTRs) and hematopoietic stem cell transplant recipients. In KTRs, persistent DNAemia has been correlated to the occurrence of polyomavirus-associated nephropathy (PVAN) that can lead to graft loss if not properly controlled. Based on recent observations that conventional dendritic cells (cDCs) specifically infiltrate PVAN lesions, we hypothesized that those cells could play a role in BKPyV infection. We first demonstrated that monocyte-derived dendritic cells (MDDCs), an in vitro model for mDCs, captured BKPyV particles through an unconventional GRAF-1 endocytic pathway. Neither BKPyV particles nor BKPyV-infected cells were shown to activate MDDCs. Endocytosed virions were efficiently transmitted to permissive cells and protected from the antibody-mediated neutralization. Finally, we demonstrated that freshly isolated CD1c+ mDCs from the blood and kidney parenchyma behaved similarly to MDDCs thus extending our results to cells of clinical relevance. This study sheds light on a potential unprecedented CD1c+ mDC involvement in the BKPyV infection as a promoter of viral spreading.

Comparison of Alemtuzumab Versus Basiliximab Induction Therapy in Elderly Kidney Transplant Recipients: A Single-Center Experience

2019 ◽  
pp. 089719001985093
Author(s):  
Idris Yakubu ◽  
Bharath Ravichandran ◽  
Tracy Sparkes ◽  
Rolf N. Barth ◽  
Abdolreza Haririan ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Loss ◽  
Survival Rates ◽  
Optimal Choice ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Risk Of Death ◽  
Single Center Experience

Background: The optimal choice of induction immunosuppression for elderly kidney transplant recipients remains unclear. Although alemtuzumab has been associated with escalating risk of death and graft loss in this population, this risk has not been adequately explored. The purpose of this study was to compare the safety and efficacy of alemtuzumab with basiliximab induction in this population. Methods: This is a retrospective matched cohort study of kidney transplant recipients aged ≥65 years. Patients who received alemtuzumab induction were matched (1:2) to a basiliximab control. The primary outcome was allograft survival. The incidence of acute rejection, infection, and all-cause mortality was measured. Results: Fifty-one and 102 patients were included in the alemtuzumab and basiliximab groups, respectively. Baseline demographics were similar between groups, except for more living donor transplant recipients in the alemtuzumab group (26/51 [51%] vs 31/102 [30.4%], P = .02). Acute cellular rejection occurred more frequently within the first year in the basiliximab group ( P = .02). There was no difference in rates of infection within the first year. Graft and patient survival rates were similar over the follow-up period. Patients receiving basiliximab had a higher glomerular filtration rate at 2 years posttransplant (59 mL/min/1.73 m2 vs 49 mL/min/1.73 m2, P = .03). Conclusions: Alemtuzumab induction is associated with similar outcomes to basiliximab in elderly kidney transplant recipients.

#77: Impact of Targeted Tacrolimus Levels on BK Polyomavirus DNAemia Among Pediatric Kidney Transplant Recipients

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S4-S4
Author(s):  
I Yildirim ◽  
R Liverman ◽  
S Serluco ◽  
R George ◽  
R Garro ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Early Onset ◽  
Bk Virus ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Intervention ◽  
Post Transplant ◽  
Bk Polyomavirus ◽  
The Impact

Abstract Background Uncontrolled BK Polyomavirus (BK) DNAemia in kidney transplant recipients is a significant cause of allograft dysfunction that can lead to BK Polyomavirus-associated nephropathy with permanent damage and graft loss. BK virus DNAemia can occur early (within the first year) or late (after the first year) following a kidney transplant in children. Prospective monitoring for BK viremia with pre-emptive lowering of immunosuppression has been suggested as an effective approach to prevent BK nephropathy. We evaluated the impact of changes in targeted tacrolimus levels on the incidence of BK DNAemia early post-transplant. Methods In response to a cluster of early-onset BK virus DNAemia cases in the first quarter of 2015, we pursued a quality improvement study to determine whether changes to tacrolimus trough targets for the first 100 days post-transplant would reduce the incidence and severity of BK DNAemia. Targeted tacrolimus levels were decreased by approximately 25% (see Table) and patients receiving transplant from March 20, 2015, and December 31, 2018, were prospectively monitored. The incidence rates of BK DNAemia detected on monthly surveillance testing in the first-year post-transplant were compared for patients transplanted between January 1, 2013, and March 14, 2015 (pre-intervention) and March 15, 2015, to December 31, 2018 (post-intervention). Results Of 148 children who received kidney transplants during the study period, 52 (35%) were transplanted in the pre-intervention era and 96(65%) were transplanted during the post-intervention era. The median age at transplant was 13.9 years [interquartile range (IQR) 8.0–16.7 years]. Age at transplant, gender (overall 55% male), and race (overall 54% White, 35% Black) was not significantly different between the cohorts. The risk of early-onset BK DNAemia within the first 100 days post-transplant was 19 per 100 patients in the pre-intervention cohort and 13 per 100 patients in the post-intervention cohort, corresponding to a 35% reduction after lowering targeted tacrolimus levels. The median time to first detected BK DNAemia increased from 77 days (IQR 45–90 days) in pre-intervention to 104 days (IQR 47–174 days) in the post-intervention cohort. Conclusions BK DNAemia heralds a serious complication of kidney transplantation and may represent over immunosuppression and increased risk for other infectious complications. We were able to reduce the rate of early-onset BK DNAemia by reducing tacrolimus target levels in the first 12 weeks post-transplant. Preventing early uncontrolled viremia may decrease the need for immunosuppression reduction which increases the risk for rejection.

Immunosuppressive Management of Pediatric Kidney Transplant Recipients

2020 ◽  
Vol 26 (28) ◽  
pp. 3451-3459
Author(s):  
Tomáš Seeman
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Graft Loss ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Therapeutic Drug ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

scholarly journals Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aziza Ajlan ◽  
Hassan Aleid ◽  
Tariq Zulfiquar Ali ◽  
Hala Joharji ◽  
Khalid Almeshari ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Controlled Trial ◽  
Controlled Clinical Trial ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Double Blind ◽  
Donor Specific Antibodies

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

Human BK Polyomavirus Nephropathy (BKVN) In Non- Kidney-Transplant Patients

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S118-S118
Author(s):  
Y Chen Wongworawat ◽  
C Zuppan
Keyword(s):  
Renal Transplant ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Transplant Patients ◽  
Bk Polyomavirus ◽  
Pathologic Features ◽  
Renal Biopsies ◽  
Renal Transplant Patients

Abstract Introduction/Objective Human BK polyomavirus nephropathy (BKVN) occurs in up to 10% of renal transplant recipients, and can result in graft loss. Transplant biopsy is the gold standard to diagnose BKVN, and SV40 immunohistochemical (IHC) staining is helpful in confirming the diagnosis. BKVN is uncommon outside the setting of renal transplantation. To understand more about its occurrence in other contexts, we reviewed our renal biopsies files for cases of BKVN. Methods Our renal biopsy files for the past 20 years were reviewed for all cases with a diagnosis of BKVN or polyoma virus infection, and the clinical characteristics of the affected patients noted. Results Evidence of BKVN was found in 44 renal biopsies, of which 39 (86%) were renal transplant patients. Of the remaining five patients (14%), two had undergone heart transplantation, one lung transplantation, one was undergoing chemotherapy for acute lymphoblastic leukemia, and one patient had active HIV infection. All patients had elevated serum creatinine, and four out of five patients had documented BK viremia. Four of the five biopsies showed typical tubular injury with viral nuclear cytopathic changes (inclusions). In the lung transplant patient, the biopsy showed advanced chronic tubulointerstitial injury without distinct viral inclusions, but SV40 staining confirmed the presence of BK virus antigen. Conclusion The BKVN is distinctly uncommon outside the context of kidney transplantation. In our series, 14% of patients with BKVN were not kidney transplant recipients, but all were immune compromised in some fashion. The pathologic features of BKVN appear similar, regardless of whether the host is a renal transplant recipient or not. Although uncommon, it is important to consider the possibility of BKVN in non-renal transplant patients with persistent or progressive renal dysfunction.

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