BK Virus Infection, Kidney Transplant; Complications
Conditions
Keywords
Immune Registry, BK in Kidney Transplant Recipients
Brief summary
Kidney transplantation (KT) is the best treatment modality available to date for patients with advanced kidney disease and the success of KT is dependent on maintaining a selective intricate balance between the risk of rejection and infections in KT recipients. BK virus is an important clinical infection affecting the post-transplant outcomes in KT recipients. BK nephropathy can affect 8-15% of patients after KT causing acute kidney injury, increased risk of rejection and fibrosis leading to additional hospital stays, increasing overall health care cost burden, and in some cases graft loss. The exact pathogenesis and treatment options for BK nephropathy are not clearly understood. It is debatable whether BK nephropathy is a full fledge donor-derived infection or reactivation of the recipient's latent infection. Irrespective of etiology, the common consensus is that treatment of BK virus infection depends on the selective restoration of host immune responses and balancing the risk of rejection vs worsening of infection.
Detailed description
As with other viral infections, adaptive immunity plays an essential role in the control of BK virus infection. Previous studies have shown that humoral immunity doesn't prevent viral reactivation and cellular responses including CD4+ and CD8+ T cells play a crucial role in containing viral replication. Researchers have investigated the role of reconstitution of BK-specific T cell immunity KT recipients with overall low immunological risk populations showing that pre and post-transplant BK virus-specific cellular responses can be used as an important tool to identify KT recipients at increased risk of developing BK virus infection in the first year post-transplant. We plan to understand the role of adaptive immunity (cellular and humoral interplay) in a cohort with at least 50% of high immunological KT recipients with predominantly retransplant candidates, highly sensitized recipients with calculated panel reactive antibodies \> 40 %, positive crossmatch or history of prior desensitization therapies. The aim includes the sequential demonstration of immunogenesis processes that are specific to the BK virus in individuals who experience BK viremia and undergo various treatment approaches such as immunosuppression reduction and immune enhancement through intravenous immunoglobulins (IVIG).
Interventions
OTHERBlood samples: Main Study group
the collection of blood samples at specified time points.
OTHERData Collection
Donor and Recipient's clinical information including clinical history, demographic characteristics labs, and imaging.
OTHERUrine Sample- Main Study group
-Post-transplant monthly urine sample collection for 6 months in 10-18% of subjects
OTHERUrine sample- Sub-study group
\- Post-transplant monthly urine sample collection for 6 months in all subjects
OTHERBlood sample: Sub-study group
Monthly blood sample collection for 6 months
Sponsors
Virginia Commonwealth University
Eurofins
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (\>18 years old) male and female, deceased donor KT recipients * Will include single organ transplants. * Each participant must also have recently been diagnosed with BK viremia. * In addition to the aforementioned inclusion criteria, each participant in the sub-study must also have recently been diagnosed with BK viremia or have difficult-to-treat BKV \> 3 logs (BKV log does not decrease by more than 1 log copy/ml drop on second per protocol lab).
Exclusion criteria
* Prisoners will not be included in the study * Multi-organ transplants and pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessing the effect of kidney transplant immunosuppression therapy on the immune response against BK virus | 24 months | Assessing the effect of kidney transplant induction and maintenance triple immunosuppression on humoral and cellular responses against BK virus compared at pre- and post-KT through clinical chart review, abnormal value or result from a clinical or laboratory evaluation, by assessing humoral and cellular responses against BK virus through BK specific T cell response, immunoglobulin G targeting BK levels, urine gene expression test to detect for BK virus and rejection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To identify the frequency risk of BK viremia | 24 month | To identify the frequency risk of BK viremia post-transplant with careful monitoring of cellular and humoral responses against BK measured using BKV T cell immunity panel test, BKV IgG test, uromap(urine gene expression test to detect for BK virus and rejection), clinical chart review and abnormal values or results from a clinical laboratory evaluation including BKV PCR. |
Countries
United States
Contacts
CONTACTAmbreen Azhar
CONTACTGelila Abebe
PRINCIPAL_INVESTIGATORAmbreen Azhar
Virginia Commonwealth University
Outcome results
None listed