Induction therapy in organ transplant procedures, consists of biologic agents to block early immune system activation.
Transplantation of allogeneic solid organs for the management of end-stage organ failure is an established modality, with more than 39,000 transplants performed annually in the United States and an overall prevalence exceeding 270,000 patients with functioning solid organ allografts.
There are more than 124,000 patients on a waiting list for organs in the United States.
Approximately 40,000 transplantations are performed yearly in the US.
In 2021 pre than 12,000 patients died or developed complications that preluded a transplant while awaiting an organ.
The number of patients on a organ waiting list increases annually despite attrition from 10,500 who die or become too sick for such transplantation.
Every 10 minutes and your name is into the national transplant waiting list.
Per patient cost of organ transplants range from $300,000 for pancreas and kidney transplants to 11/2 million dollars for intestinal transplants.
Mean survival benefit from organ transplants spans from 2.4 years in pancreas recipients to 4.9 years in heart recipients.
Prolonged exposure of transplant recipients to immunosuppressive agents can lead to long-term medical complications, including chronic kidney disease: up to 18% of liver transplant recipients developed renal failure within five years after transplant, and those that require dialysis have good poor survival of 27% at six years (Gonwa TA et al, Diederich D et al).
Organ recovery occurs from three sources: neurologic deaths, controlled circulatory death, and live donors for kidneys and partial livers.
For most transplants, a negative final crossmatch by flow cytometry is the single best clinical indicator of a successful transplant.
Cancer is the leading cause of morbidity and mortality in solid organ transplant recipients, with a greater than twofold higher cancer incidents compared with the US general population.
This cancer burden is expected to increase in association with increasing the number of transplants performed, longer graft survival, older recipient age, and a decline in the competing risk of cardiovascular
A recent US retrospective study documented that skin cancers are the most common cancer affecting 8% of transplant recipients: cutaneous squamous cell carcinoma is the dominant histology with 91% of skin cancer diagnoses, followed by melanoma, 8%, and Merkel cell carcinoma less than 1%.
the incidence rate of 100,000 person-years for cutaneous squamous cell carcinoma was 36 times higher than for the US general adult population.
The great majority of post-transplant lymphomas are non-Hodgkin’s lymphomas.
Lymphomas account for 22% of all posttransplant cancers are according to other studies.
Much of the increased risk of cancer associated with organ transplantation is a consequence of chronic immunosuppressive agents targeting T-cell alloimmunity required for graft survival.
Chronic immune suppression blunts T- cell recipient responses specific for viral and non-viral antigens, including mutation associated antigens contributing to impaired immune surveillance against transformed cells.
The brain accounts for 26% of non-Hodgkin’s lymphomas in the transplant population.
Cardiovascular disease common after hepatic and renal allograft, and contributes to morbidity and death in these patients.
Renal and hepatic transplant patients develop cardiovascular disease at an earlier age than non-transplant recipients.
Spectrum of infections after organ transplantation has changed with number of opportunistic infections caused by Cytomegalovirus and Pneumocystis decreasing and those caused by antimicrobial resistant bacteria having increased.
Opportunistic infections that occur early after solid organ transplantation can be de novo or reactivation of a latent infection.
Common solid organ post transplant opportunistic infections include cytomegalovirus, fungal pathogens, including Aspergillus and Candida, and bacterial agents such as Pneumocystitis jiroveci and Mycobacteria tuberculosis.
Donor derived infections have been described but are uncommon in allotransplantation.
Unexpected donor-derived infections occur in approximately 0.2% of transplantation in the US and include infections due to organisms that area undetected in current donor screening.
Pre-and post transplantation surveillance for HIV, HBV, and HCV in organ recipients is required
Chronic kidney disease is a common complication of nonrenal solid organ transplantation.
Potency of new immunosuppressive agents have increased and have the ability to prevent or treat acute T cell mediated cellular rejection rates to less than 15%.
Cumulative incidence of chronic kidney disease highest among those with intestine allografts at 21.3% followed by liver recipients at 181%, lung transplants at 15.8%, heart at 10.9% and heart-lung at 6.9%.
The risk of developing chronic renal disease increases with the interval since transplantation.
Approximately 29% of patients with chronic renal disease after nonrenal solid organ transplantation require renal replacement therapy.
Diabetes is a complication of solid organ transplantation and contributes to chronic renal disease.
Following solid organ transplantation there is a significantly high risk of osteoporosis and bone fracture during long-term follow-up:pre-existing underlying diseases and immunosuppressive therapy for important factors in the development of bone disease in such patients.
Weight gain after solid organ transplantation is an important predisposing factor for the development of diabetes after transplantation, and the risk is further increased by exposure to corticosteroids and the calcineurin inhibitor agents tacrolimus and cyclosporine.
The development of chronic renal disease after nonrenal solid organ transplant increases the risk of death by a factor of 4.
Hypertension occurs in 80% of transplant recipients related to calcineurin inhibitors and corticosteroids.
Chronic renal disease after solid nonrenal transplant increases with older age, female gender, use of immunosuppressive treatment with calcineurin inhibitors, impaired glomerular filtration rate, the presence of hypertension, diabetes, the presence of acute renal failure before or at the time of transplantation and the need for dialysis.
The incidence of chronic renal disease in nonrenal solid organ transplant patients has decreased related to more judicious use of immunosuppressive agents in recent years.
The use of induction therapy in organ transplant recipients attemps to intensify immunosuppression durung the peritransplantation period contributing to a reduction in early rejection rates and graft loss in the first year after iransplantation.
As of 2008 82% of renal, 57% of lung and 26% of liver transplant recipients received such induction agents.
Induction therpay increasingly utilized in patients with repeat transplantations, sensitized patients and in patients with high frequency of donor specific T cell precursors, and in patients needing to minimize toxic maintenance therapy of calcineurin inhibitors or corticosteroids.
Treatment protocols for ABO incompatibility include combinations of B cell depletion, removal of isohemagglutinins through plasmapheresis or immunoadsorption and augmented immunosuppression.
Smoking in solid organ transplant donors and recipients is associated with increase in graft loss, cardiovascular events, malignancy, and mortality.