New NephSAP issue - "Transplantation"

By ASN Staff

NephSAP Volume 16, Number 4, November 2017

Find the full issue here.

Transplantation

The total number of kidney transplant recipients alive with a functioning graft is now greater than 200,000 in the United States.  Graft failure rates are slowly but significantly improving; however, death with intact function rates remain constant. Analysis of the major changes to kidney allocation implemented in December 2014 reveal improvements in net quality-associated life-years at lower cost than the prior system. There have also been improvements in access for minorities, younger candidates, and those who are highly sensitized, at the expense of reduced access for older patients and higher delayed graft function rates. Deceased donor kidneys procured from individuals who meet the US Public Health Service definitions of increased risk now comprise 20% of the donor pool. Unfortunately, the number of living donors has declined in the United States despite increasing Kidney Paired Donation efforts. Post- nephrectomy surgical complications occur in approximately 17% of donors, and are more common in blacks, the obese, and those with hematologic or psychiatric conditions. Fortunately, the risk of higher grade complications is lower at 2.5%. Gestational hypertension and preeclampsia are more common in living donors than non-donors. Live kidney donors experience a small but higher incidence of ESRD compared with nondonors. Donor, peritransplant, and recipient factors are implicated in the pathogenesis of delayed graft function, which impacts patient and graft survival adversely. The requirement for midodrine pre-transplant has been recently identified as a risk factor for delayed graft function.

Most patients receive antibody induction therapy at transplantation and maintenance therapy with tacrolimus, mycophenolate, and steroid. Tacrolimus remains the single, most effective maintenance immunosuppressive agent available to prevent acute allograft rejection. Prospective, elimination studies in low risk kidney allograft recipients have yielded unacceptable results. Maintenance of therapeutic levels remains of critical importance for all transplant recipients. Mycophenolate dose reductions post-transplant are associated with increased risk  of graft loss. Steroid avoidance and withdrawal are associated with increased risk of allograft rejection. The use of the mTOR inhibitors, sirolimus and everolimus, continues to decline due to unfavorable efficacy and adverse event and outcome measures compared with calcineurin inhibition

Post-transplant transfusion is associated with risk of donor-specific antibody development and antibody-mediated rejection. The development of donor-specific antibody and antibody-mediated rejection, whether clinical or subclinical, impacts graft survival adversely. Non-adherence is associated with increased risk of rejection as HLA mismatches increase. Patient and graft survival rates for ABO-compatible and preconditioned ABO-incompatible transplants are generally equivalent. Desensitization to permit HLA=incompatible transplant associates with antibody-mediated rejection and inferior outcomes. Experimental tolerance induction utilizing transient or persistent donor chimerism have led to durable engraftment for a limited number of human transplant recipients.

Transplant recipients who are seronegative for BK virus and receive seropositive grafts (D+/R-) are at increased risk of BK viremia. Transplant recipients co-infected with HIV and HCV have markedly inferior graft survival rates compared to mono-infected or non-infected individuals. The incidence of bone fracture post-transplantation has declined over time, concurrent with increasing use of bisphosphonate prophylaxis. Bisphosphonate use is associated with improvements in bone density, although not directly linked to reducing fracture risk.

Learning Objectives:

  1. Describe current transplant outcomes, including delayed graft function, rejection, graft, and patient survival, and living donor outcomes
  2. Discuss early outcomes associated with the 2014 changes to the Kidney Allocation System
  3. Examine the spectrum of complications that occur after transplantation, including infection, malignancy, and cardiovascular disease, and accompanying individual diagnostic and therapeutic strategies
  4. Review the status of immunosuppression, incompatible transplantation, and efforts to achieve immunologic tolerance
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NephSAP Volume 16, Number 4, November 2017

Find the full issue here.

Transplantation

The total number of kidney transplant recipients alive with a functioning graft is now greater than 200,000 in the United States.  Graft failure rates are slowly but significantly improving; however, death with intact function rates remain constant. Analysis of the major changes to kidney allocation implemented in December 2014 reveal improvements in net quality-associated life-years at lower cost than the prior system. There have also been improvements in access for minorities, younger candidates, and those who are highly sensitized, at the expense of reduced access for older patients and higher delayed graft function rates. Deceased donor kidneys procured from individuals who meet the US Public Health Service definitions of increased risk now comprise 20% of the donor pool. Unfortunately, the number of living donors has declined in the United States despite increasing Kidney Paired Donation efforts. Post- nephrectomy surgical complications occur in approximately 17% of donors, and are more common in blacks, the obese, and those with hematologic or psychiatric conditions. Fortunately, the risk of higher grade complications is lower at 2.5%. Gestational hypertension and preeclampsia are more common in living donors than non-donors. Live kidney donors experience a small but higher incidence of ESRD compared with nondonors. Donor, peritransplant, and recipient factors are implicated in the pathogenesis of delayed graft function, which impacts patient and graft survival adversely. The requirement for midodrine pre-transplant has been recently identified as a risk factor for delayed graft function.

Most patients receive antibody induction therapy at transplantation and maintenance therapy with tacrolimus, mycophenolate, and steroid. Tacrolimus remains the single, most effective maintenance immunosuppressive agent available to prevent acute allograft rejection. Prospective, elimination studies in low risk kidney allograft recipients have yielded unacceptable results. Maintenance of therapeutic levels remains of critical importance for all transplant recipients. Mycophenolate dose reductions post-transplant are associated with increased risk  of graft loss. Steroid avoidance and withdrawal are associated with increased risk of allograft rejection. The use of the mTOR inhibitors, sirolimus and everolimus, continues to decline due to unfavorable efficacy and adverse event and outcome measures compared with calcineurin inhibition

Post-transplant transfusion is associated with risk of donor-specific antibody development and antibody-mediated rejection. The development of donor-specific antibody and antibody-mediated rejection, whether clinical or subclinical, impacts graft survival adversely. Non-adherence is associated with increased risk of rejection as HLA mismatches increase. Patient and graft survival rates for ABO-compatible and preconditioned ABO-incompatible transplants are generally equivalent. Desensitization to permit HLA=incompatible transplant associates with antibody-mediated rejection and inferior outcomes. Experimental tolerance induction utilizing transient or persistent donor chimerism have led to durable engraftment for a limited number of human transplant recipients.

Transplant recipients who are seronegative for BK virus and receive seropositive grafts (D+/R-) are at increased risk of BK viremia. Transplant recipients co-infected with HIV and HCV have markedly inferior graft survival rates compared to mono-infected or non-infected individuals. The incidence of bone fracture post-transplantation has declined over time, concurrent with increasing use of bisphosphonate prophylaxis. Bisphosphonate use is associated with improvements in bone density, although not directly linked to reducing fracture risk.

Learning Objectives:

  1. Describe current transplant outcomes, including delayed graft function, rejection, graft, and patient survival, and living donor outcomes
  2. Discuss early outcomes associated with the 2014 changes to the Kidney Allocation System
  3. Examine the spectrum of complications that occur after transplantation, including infection, malignancy, and cardiovascular disease, and accompanying individual diagnostic and therapeutic strategies
  4. Review the status of immunosuppression, incompatible transplantation, and efforts to achieve immunologic tolerance
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Date:
Wednesday, November 15, 2017