Solid Organ Transplant: The Basics PDF

Solid Organ Transplant: The Basics Chelsea Wernsdorfer, CRNP [email protected] Important Data Points ► Over 42,000 people in the US received some form of transplant in 2022. ► Survival rates of transplanted grafts continue to improve. ► There are over 104,0...

Solid Organ Transplant: The Basics Chelsea Wernsdorfer, CRNP [email protected] Important Data Points ► Over 42,000 people in the US received some form of transplant in 2022. ► Survival rates of transplanted grafts continue to improve. ► There are over 104,000 people currently on the waitlist for transplants. ► 90% of US adults say they support organ donation, but only 60% are registered. HRSA organ donor.gov Retrieved from HRSA organdonor.gov Definitions ► Organ transplantation is the removal of organs from one person(donor) and the surgical implantation of those organs into another person (recipient). ► Immunosuppression of the recipient is required to continue the healthy function of the donor organs, otherwise the recipient risks rejection. ► Rejection is the activation of the recipient’s immune system, and targeting of the donor organ History ► 1954 - 1st successful renal transplant in North America ► 1963 – first lung transplant, first liver transplant ► 1967 – first successful heart transplant, first successful liver transplant ► 1983 – first successful lung transplant ► In September of 2022, the total number of organ transplants performed in the US (since 1988, the first year national transplant data was collected ) reached one million. What Gets Transplanted Vascular Composite Allografts Organs and other Tissues Hands Heart Face Lungs Penis Liver Uterus Pancreas Kidney Intestine Bone Marrow, blood products, corneas  Graft Survival Organ Type 1 Year 5 year Heart 91% 78% Lung 87.75% 52.5% Liver 93.27% 72% Living Donor Kidney 98.46% 85% Deceased Donor Kidney 97.5% 80% Pancreas 95% 74.5 This column based on 2011-2015 data Data from https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/ VCA – face, uterus, penis, limbs ► Data is still limited as not many have been done ► 18 total cranio-facial performed 2008-2020, 39 uterine, 19 Bilateral upper extremity, 18 unilateral, 2 penile https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/ Waitlist Stats Waitlist additions = 21,000 But also Waitlist mortality increased in 2020 for kidney, lung and liver From: https://insights.unos.org/OPTN-metrics/ Who Gets Transplanted? Eligibility: Contraindications: ► End-stage organ disease ► Active substance use despite best medical ► Active infection management ► Active CA ► Otherwise healthy ► Psycho-social ► Social support in place ► Medical instability ► Medical need ► Obesity/cachexia ► Geography https://optn.transplant.hrsa.gov/professionals/by-topic/ethical-considerations/general-considerations-in-assessment-for-transplant-candidacy/ A Quick Surgical Overview Kidney Transplant https://www.mayoclinic.org/tests-procedures/kidney-transplant/about/pac-20384777 Deceased Donor- Traditional Liver Transplant https://www.mayoclinic.org/departments-centers/transplant-center Living Donor- Split Graft https://www.mayoclinic.org/departments-centers/transplant-center Pancreas Transplant From Mayo Clinic https://www.mayoclinic.org/tests-procedures/pancreas-transplant/about/pac-20384783  Heart Transplant https://www.mayoclinic.org/tests-procedures/heart-transplant/about/pac-20384750  Bilateral Lung Transplant From https://med.emory.edu/education/vme/pages/gallery/pf-transplant-textbook.html and https://www.mayoclinic.org/tests-procedures/lung-transplant/about/pac-20384754  Face Transplant https://people.com/human-interest/patrick-hardison-first-extensive-face-transplant-life-year-after-surgery/  Hand/Arm From JHU! Uterus Will still need to undergo in vitro fertilization Uterus removed after birth of child From https://www.nytimes.com/2015/11/13/health/uterus-transplants-may-soon-help-some-infertile-women-in-the-us-become-pregnant.html Penile Transplant Goal is return of full function, urinary and sexual Too few performed for good data on long-term outcomes Lake, et al 2022 Post-surgical Support General – ICU vs. IMC Organ Specific ► Pain management – lungs ► Heart – hemodynamic support, pacer & pancreas ► Lungs – pulmonary support, ► Restore function – organ pulmonary toilet system, rehabilitation ► Kidney – fluids and ► Initiate electrolytes, bladder drainage ► Pancreas – blood glucose, immunosuppression bowel function ► Liver – LFTs, “other” LFTs, biliary drainage Possible Post-Surgical Complications ► Bleeding vs Thrombosis ► Vascular stenosis - renal, pulmonary ► Wound infection ► Interrupted lymphatics – lymphocele, seromas ► Luminal disruption - ureter, small bowel, bile duct, bronchus, ► Nerve injuries / denervation - vagus, phrenic, ► Ischemia – Reperfusion ► Aspiration Medical Management: Immunosuppression Immunosuppression: a snapshot of the immune system Immunosuppression ► Three phases 1st: Induction 2nd: Maintenance 3rd: Rescue Immunosuppression ►Useful for demonstrating the different areas that IS agents target. ►APC is antigen presenting cell (i.e. cell of new organ) Induction ► Given in the peri-procedural timeframe – often started during and continued in divided doses afterwards. ► The goal is to massively suppress the immune system and delay recognition of new organ as foreign – and so delay Rejection Diaz, Duncan  Induction ► Some common induction agents: Thymoglobulin ( T-Cell Ab) Campath (T cell Ab) Basiliximab (IL 2 interceptor) High dose IV steroids ► Uncommon agents (disease specific and rare): Rituximab Eculizumab Diaz, Duncan Induction: Adverse Effects and Possible Side Effects ► Cytokine release syndrome*** ► Anaphylaxis ► Serum sickness – high temps, arthralgias, rash ► Pancytopenia ► Profound TCP and leukopenia ► Flash pulmonary edema ► Seizures ► Increased long-term risk infections and malignancy Pic from https://www.rch.org.au/serum_sickness/ Maintenance ► Triple therapy, at least at outset – goal is long-term graft survival Calcineurin inhibitors: most common are tacrolimus and cyclosporin o Trough levels required Mycophenolate mofetil, sometimes azathioprine o Also will sometimes see rapamune and everolimus (mTOR inhibitors) Steroids Diaz, Duncan, Liver Transplantation Maintenance: Monitoring Calcineurin Inhibitors Tacrolimus Cyclosporine ► Trough levels ► Trough levels ► Nephrotoxic ► Nephrotoxic ► Tremor/Headache ► Tremors ► Change in MS ► Hepatotoxic ► Alopecia ► Hirsutism ► Hyperglycemia ► Gingival hyperplasia ► Hypertension ► Hypertension ► Hypomagnesemia ► hypomagensemia Hussain 2022 Maintenance: Monitoring MMF and Rapamune MMF Rapamune ► No troughs ► Trough level ► GI distress ► Pancytopenia ► Neutropenia ► Delayed wound healing ► Goal is 1 gram BID, ► Black box warning for weaned down per center liver transplant (still gets preference used) Hussain 2022  Maintenance: Monitoring ► Everolimus Nephrotoxicity Delayed wound healing Hyperglycemia Diarrhea ► BUT, interestingly enough HAT reduced May reverse immunosenescence (does in mice) Hussain 2022  Maintenance: Monitoring Steroids ► Prednisone Appetite stimulation Hypertension Hyperglycemia Delayed wound healing Myopathy Osteoporosis Aseptic necrosis of hip/ shoulder joints Peptic ulcers Skin thins, more acne Irritability Hussain 2022 A Delicate Balance Prophylaxis: common infections post- transplant Galliford, J., & Game, D. S. (2009). Journal of Postgraduate Medicine, 85, 91-101  Common Prophylactic agents ► PCP Pneumonia Bactrim DS Dapsone Pentamidine ► Fungal Prophylaxis Nystatin swish and spit Fluconazole Clotrimazole Amphotericin B Nebs ► CMV Valganciclovir vs. acyclovir Fishman, 2007 New and Coming Soon to a Transplant Near You! ► Hepatitis C positive donors Previously discarded organs Often in good shape DAA starting about 3-6 weeks post-transplant ► HIV positive donors Given to HIV positive recipients HAART given continuously Zahid, 2022; OPTN Hope Act Rejection All transplanted patients will have some episode of rejection, be it mild or more serious Takemoto, 2007 HLA ► HLA or human leukocyte antigen ► There are multiple alleles – but three of importance – A, B and DR ► Tracked prior to transplant – most important to kidney, and heart ► HLA mismatch per-disposes to B- cell humoral or Antibody-mediated rejection (AMR) Choo, 2007  Signs and Symptoms of Rejection ► Signs are graft dependent Pain over graft site Lab abnormalities Sometimes a “failure to thrive” picture Biopsy is the gold standard for diagnosis Takemoto,2007  Treatment of Rejection ► Two Mechanisms: 1) Cellular – T cell mediated and inflammatory in nature, organ recognized as foreign – treated with steroids 2) Humoral – B cell mediated, harder to squash. Treated with Thymoglobulin, or if very stubborn with Plasmapheresis and gamunex as well. Choo, 2007  Other Complications ► Malignancy 3-4x increase in all types CA – but most commonly seen is skin CA ► PTLD: Post-Transplant Lymphoproliferative Disorder Over production of EBV infected B cells Treated with reduction of IS Fishman, 2007 Other Complications ►Graft vs. Host The graft co-opts the host immune cells and attacks the host tissue ►Common in stem cell transplant ►Rare in other organ transplant and quite deadly ►Treatment: varies, steroids, MABs, or reducing IS https://www.cancer.gov/news-events/cancer-currents-blog/2017/ibrutinib-fda-gvhd Non-Compliance ► Risks for non-compliance Youth Visual or other sensory impairment Low literacy SES Mental illness Gandolfini, 2022 References Choo, S. Y. (2007). The HLA system: genetics, immunology, clinical testing, and clinical implications. Yonsei Medical Journal, 48(1), 11–23. https://doi.org/10.3349/ymj.2007.48.1.11 Diaz, J.F. (2009). Survival Guide: A quick access guide to the care of kidney transplant recipients. Internal Report. Comprehensive Transplant Center, Johns Hopkins Hospital. Unpublished. Duncan, M. D., & Wilkes, D. S. (2005). Transplant-related immunosuppression: A review of immunosuppression and pulmonary infections. Proceedings of the American Thoracic Society, 2(5), 449–455. https://doi.org/10.1513/pats.200507-073JS Fishman, J. A. (2007). Infection in solid-organ transplant recipients. New England Journal of Medicine, 357(25), 2601-2614. 10.1056/NEJMra064928 Galliford, J., & Game, D. S. (2009, February). Modern renal transplantation: Present challenges and future prospects. Postgraduate Medical Journal. DOI: 10.1136/pgmj.2008.070862 Gandolfini, I., Palmisano, A., Fiaccadori, E., Cravedi, P., & Maggiore, U. (2022). Detecting, preventing and treating non-adherence to immunosuppression after kidney transplantation. Clinical Kidney Journal, 15(7), 1253–1274. https://doi.org/10.1093/ckj/sfac017 Grim S. A., Clark, N. M. (2011). Management of infectious complications in solid-organ transplant recipients. Clinical Pharmacology and Therapeutics, 90(2), 333-342. doi: 10.1038/clpt.2011.90. Epub 2011 Jun 29. Hussain, Y., & Khan, H. (2022). Immunosuppressive drugs. Encyclopedia of Infection and Immunity, 726–740. https://doi.org/10.1016/B978-0-12-818731-9.00068-9 Lake, I. V., Girard, A. O., Lopez, C. D., Cooney, D. S., Burnett, A. L., Brandacher, G., Oh, B. C., & Redett, R. J. (2022). Penile transplantation: Lessons learned and technical considerations. The Journal of Urology, 27(5), 960-968. https://doi.org/10.1097/JU.0000000000002504 Liver transplantation: Vol 26, No 1. (n.d.). Retrieved from https://aasldpubs.onlinelibrary.wiley.com/toc/15276473/2020/26/1 Nci, NCI Staff, & Nci. (n.d.). Ibrutinib approved for graft-versus-host disease. Retrieved from https://www.cancer.gov/news-events/cancer-currents-blog/2017/ibrutinib-fda-gvhd Organ Donation Statistics. (2023, March). Retrieved from https://www.organdonor.gov/statistics-stories/statistics.html Organ Procurement and Transplantation Network. (n.d.). Retrieved from https://optn.transplant.hrsa.gov/data/organ-datasource/ Takemoto, S. K., Zeevi, A., Feng, S., Colvin, R. B., Jordan, S., Kobashigawa, J., Kupiec-Weglinski, J., Matas, A., Montgomery, R. A., Nickerson, P., Platt, J. L., Rabb, H., Thistlethwaite, R., Tyan, D., & Delmonico, F. L. (2004). National Conference to Assess Antibody-Mediated Rejection in Solid Organ Transplantation. American Journal of Transplantation, 4(7), 1033- 1041. 10.1111/j.1600-6143.2004.00500.x Transplant Center. (2019, October 10). Retrieved March 25, 2023, from https://www.mayoclinic.org/departments-centers/critical-care/sections/tests-procedures/orc-20399607 Zahid, M. N. (2022). Transplantation of organs from Hepatitis C virus-positive donors under direct-acting antiviral regimens. Journal of Clinical Medicine, 11(3), 770. https://doi.org/10.3390/jcm11030770