6 research outputs found
FP347THE REAL-WORLD WORKLOAD AND HEALTH ECONOMIC CONSIDERATIONS OF INITIATING A TREATMENT FOR ADULT POLYCYSTIC KIDNEY DISEASE
No full textFP146RENAL BIOPSY COMPLICATION RATES AND TRANSFUSION REQUIREMENTS IN A TERTIARY TEACHING HOSPITAL
No full textA transitional B cell cytokine biomarker for risk stratifying renal transplant patients with borderline rejection
No full textBorderline allograft rejection can promote acute rejection and graft loss in some, but not all, patients. In this issue, Cherukuri et al. use a novel test based on peripheral blood transitional T1 B cells producing interleukin-10 and tumor necrosis factor-α, which identifies patients at high risk for poor outcomes. The potential mechanisms by which transitional T1 B cells might modulate alloreactivity need exploration, but following appropriate validation, this biomarker could risk stratify patients in need of early intervention.</p
Activation and regulation of indirect alloresponses in transplanted patients with donor specific antibodies and chronic rejection
No full textFollowing transplantation, human CD4+T cells can respond to alloantigen using three distinct pathways. Direct and semi-direct responses are considered potent, but brief, so contribute mostly to acute rejection. Indirect responses are persistent and prolonged, involve B cells as critical antigen presenting cells, and are an absolute requirement for development of donor specific antibody, so more often mediate chronic rejection. Novel in vitro techniques have furthered our understanding by mimicking in vivo germinal centre processes, including B cell antigen presentation to CD4+ T cells and effector cytokine responses following challenge with donor specific peptides. In this review we outline recent data detailing the contribution of CD4+ T follicular helper cells and antigen presenting B cells to donor specific antibody formation and antibody mediated rejection. Furthermore, multi-parametric flow cytometry analyses have revealed specific endogenous regulatory T and B subsets each capable of suppressing distinct aspects of the indirect response, including CD4+ T cell cytokine production, B cell maturation into plasmablasts and antibody production, and germinal centre maturation. These data underpin novel opportunities to control these aberrant processes either by targeting molecules critical to indirect alloresponses or potentiating suppression via exogenous regulatory cell therapy
Older Kidney Transplant Patients Are Over Immunosuppressed Using Standard Protocols With Differential Sex‐Based Complications
No full textBackgroundIncreasing numbers of older patients are undergoing kidney transplantation. While there is evidence for both sex- and age-related immunological variations increasing the risks of immunosuppression (IS), few centers enforce age- or sex-specific IS adjustments.MethodsWe investigated outcomes of 148 kidney transplants performed in our center between April 2009 and March 2019 in recipients aged > 60 years and compared them to outcomes in 272 younger recipients (divided into age groups 18–34, 35–49, and 50–60 years), matched for degree of human leukocyte antigen (HLA) sensitization (calculated reaction frequency, cRF), number of donor–recipient HLA mismatches, and cytomegalovirus (CMV) serostatus, all treated with the same IS protocol. Outcomes were time to (i) first episode of biopsy-proven acute rejection (BPAR), (ii) first CMV viremia within the first 6 months, (iii) incidence of any new-onset malignancy, and (iv) development of donor-specific anti-HLA antibodies (DSAs).ResultsOverall rates of BPAR were highest in the recipients under the age of 35, but with no evidence of a difference between older age groups. Conversely, the risk of CMV viremia and malignancy was significantly higher in older recipients; in the > 60-year-old group, CMV viremia HR: 2.66 (95% CI: 1.49–4.75), and malignancy HR: 7.3 (95% CI: 1.7–31.10) versus the youngest group with little evidence was confounded by comorbidity or donor factors on multivariate analysis. The risk of CMV infection was most marked in the oldest female group, while the risk of malignancy was greatest in older males. The development of DSA was equal across all age groups.ConclusionOur data indicate that older recipient age is associated with increased risk of CMV viremia and malignancy after transplantation, suggesting an age-associated vulnerability to IS, with the risk occurring mostly in older women and older men, respectively. These data support the need to develop age- and sex-specific protocol adjustments
Older Kidney Transplant Patients Are Over Immunosuppressed Using Standard Protocols With Differential Sex-Based Complications
No full textBACKGROUND:
Increasing numbers of older patients are undergoing kidney transplantation. While there is evidence for both sex‐ and age‐related immunological variations increasing the risks of immunosuppression (IS), few centers enforce age‐ or sex‐specific IS adjustments.
METHODS:
We investigated outcomes of 148 kidney transplants performed in our center between April 2009 and March 2019 in recipients aged > 60 years and compared them to outcomes in 272 younger recipients (divided into age groups 18–34, 35–49, and 50–60 years), matched for degree of human leukocyte antigen (HLA) sensitization (calculated reaction frequency, cRF), number of donor–recipient HLA mismatches, and cytomegalovirus (CMV) serostatus, all treated with the same IS protocol. Outcomes were time to (i) first episode of biopsy‐proven acute rejection (BPAR), (ii) first CMV viremia within the first 6 months, (iii) incidence of any new‐onset malignancy, and (iv) development of donor‐specific anti‐HLA antibodies (DSAs).
RESULTS:
Overall rates of BPAR were highest in the recipients under the age of 35, but with no evidence of a difference between older age groups. Conversely, the risk of CMV viremia and malignancy was significantly higher in older recipients; in the > 60‐year‐old group, CMV viremia HR: 2.66 (95% CI: 1.49–4.75), and malignancy HR: 7.3 (95% CI: 1.7–31.10) versus the youngest group with little evidence was confounded by comorbidity or donor factors on multivariate analysis. The risk of CMV infection was most marked in the oldest female group, while the risk of malignancy was greatest in older males. The development of DSA was equal across all age groups.
CONCLUSION:
Our data indicate that older recipient age is associated with increased risk of CMV viremia and malignancy after transplantation, suggesting an age‐associated vulnerability to IS, with the risk occurring mostly in older women and older men, respectively. These data support the need to develop age‐ and sex‐specific protocol adjustments
