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45 Cards in this Set
- Front
- Back
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ESRD |
projected to contrinue to rise incidence with the increasing prevalance of diabetes in US most common form of mgmt is hemodiaylsis, with transplants as the least common but increasing slowly in prevalance |
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Incident counts by race |
Counts are increasing for black and americans but the rates are starting to decline |
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Causes of ESRD |
diabetes is the most common in prevalance and incidence then hypertension, then GN, then PCKD, other and unkown |
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Mgmt of CKD |
either hemodiaylsis then renal transplant peritoneal dialysis then transplant or transplant |
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Relative risk of renal transplant vs diaylsis |
relative risk of death goes from 2.84 to .32 after 2 years post transplant transplant patients have a greater number of quality years of life line to get transplant is continuing to grow and the age of that population is growing as well |
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Elderly patients |
only after about 1.8 yrs post transplant does the transplant survival curve equal the wait list dialysis, due to complications from surgery and decreased healing in elderly |
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trends in transplantation |
incidence rate is increasing but the transplant rate is decreasing given the rate of ESRD due to its faster growth than transplant can maintain incidence of waitlist is growing as wells as transplant counts from both deceased and living donors |
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History of renal transplants |
first long term success were identical twins in 1954, recipient survived over 1 year by 1966 using direct cross match between donor lymphocytes and reicipent serum |
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Deceased vs living donor |
deceased donors are less probable to result in survival compared to living donors |
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Blod typing |
donor and recipient must be ABO compatible endothelial cells have A or B antigens most people have antibodies to the antigens they lack O is the most common waitlisted blood type |
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HLA typing |
donor and recipient HLA alleles, HLA A B and DR are the most impt each person has two alleles for each constituting 6 antigens to compare importance of other antigens increasing especaillay in relationship to antibodies developing late post Tx |
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PRA |
panel reactive antibody reflected as a percentage which relates to presence of Abs to HLA molecules the higher the PRA the more sensitized the recipient is ie more like to have rejection |
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High PRA |
pregnancy, blood tranfusions, prior transplant, essentially you are high risk for rejection |
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Attempts to increase the donor pool |
use of organs from expanded donor pool, older age 50-59 pluse two of the collowing creatinine about 1.5 HTN or CVA, non heart beatinf donors systematic targeted educational campaigns |
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efficacy of ECD kidneys |
should be offered to principally to candidates older than 40 years in OPOs with long wait time in OPOs with shorter waiting times, in which non ECD kidney transplant availability is higher candidates should be counseled that ECD survival benefit is observed only for patients with beetus |
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Kidney wait list |
Kidney Donor Patient Index KDPI desides who would get the kdiney variables are age, height, weight, ethnicit, HTN, DM, cause of death, HCV status, DCD status |
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Why is living donation so much more successful |
defies the importance of HLA matchin, testament to new drug therapies, raises the issue of increased Ag presenation in death |
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Alloantigen dependent mechanisms |
HLA matching, acute rejection, ongoging subclinical immune injury which causes B cell and T cell development to trigger atack of endothelium of new kdiney and leads to chronic rejection |
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Alloantigen independent mechanism |
brain death, ichemic injury, inadequate reanl mass, hypertension and hyperlipidemia, drug nephrotoxicity CMV and other infections can exacebate the immune response and cause direct injury to the tissue |
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Pre transplant eval |
target risks for infection, Cv disease, malignancies includes a comprehensive physical and history as well as serologic studies |
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Surgical procedue for living donors |
open surgery with large incision to flank or laproscopic removal of kidney can be used with good results |
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Cross matchin |
B and T cell cross match donor lymphocytes are incubated against recipient serum, determines if recipient has circulating Abs to MHC antigens of the donor, can eliminate the chance of hyperacute rejection |
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Types of rejection |
hyperacute, occurs within minutes to hourse of release of clamps accelerated = occurs within 24 hrs to 4 days after transplant acute, days to weeks chronic months to years |
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hyperacute rejection |
irreversible result of preformed circulating antibodies very rare is cross match is negatice results in complement activation and thrombosis, vascular injury, ischemia and graft loss |
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acceleated acute rejection |
occurs within 1-4 days results of prior sensitixation of the receopient to donor antigets via prior transplant or transfusion mediated by both cellular and humoral immunity difficult to treat |
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acute rejection |
90% are cellular mediated 5-10 are humoral easier to treat constitutional symptoms present due to cytokine release pathology; tubulitis, vasculitits and perivascular infiltration |
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Chronic rejection |
months to years etiology not clearly known but probably multifactorial late developing donor specific antibodies play a key role |
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Ab mediated rejection |
development of donor specific anti HLA abs following tranplant against class II antigens no immunosuppressives approved to treat less reponsive to antirejection therapy late AMR is associated wiht lower long term graft survival than early AMR new therapies on the rise |
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Immunosuppresion mechanisms |
deplete lymphocytes divery lymphocyte traffic block lymphocyte response pathways |
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Common drugs in maintenance |
cyclosporine tacrolimus prenisone azathiiprine mycophenolate sirolumus belatocept |
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Induction of rescue drugs |
basiliximab, daclizumab OKT3 ATGAM and thymglobulin Campath ih |
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Current immunosuppresion |
corticosteroids, inhiito prpduction of interluekins in lymph traficing, many side effects, withdrawal can lead to rejection |
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Inhibitors of purine/pyriminde syn |
azathiprine mycophenolate MMF resulted in less accute rejection than AZA ina randomized trial and may be effective for chronic rejection |
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Antilymphocyte Abs |
bind to lymphoytes and trigger cel death via complement of Fc recepotr mediated lysis polyclonal are ATGAM monoclonal OKT3 Anti IL2 receptor abs are dacilizumad and basilizimad |
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Rapamycin |
sirolimus, attachs to TOR on calineurin decreases the incdience of acute rejection permiets smaller doses of other drugs toxititis to other organs |
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Axioms of immunsuppresion |
three effects: immunosuppressive effect ISE, immunodeficient complications IDT and non immune toxicity NIT NIT is dose limiting combos are used to increase ISE but no NIT ISE and IDT are linked and equal therapeutic index = ISE/NIT |
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Integrated phamacologic model for immunosuprpresion |
patient factors = race, gender, genetic variation, immune funciton, co morbid disease with significant immune responsiveness to the graft immunosuppressive therapy, indidivudal drug pharmacokinetics, drug-drug interactions, and drug-disease interactions can lead to different lcinical outcomes |
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P-glyocprotein CYP3A4/5 |
increased exprssion of the p- glycoprotein results in increased pumping of the drugs into the bile ducts, into the proximal tubule, and into the intestinal lumen resulting in decreased absorption |
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tolerance-chimerism |
tolerance = maintenance of graft with no ongoing immunosuppresion chimerism - host cells are a mixture of donor and recipient microchimerism is chimerism can be demonstrated in a very small percent of host cells more likely to result when donor immune system manipulated prior to tranplant, simultanteous immune cell infection, aggressive early immunosuppresison follow by low dose |
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Tranplant malignancies |
most commmon transplant is kidney and the most common tissue of malignancy orihion is skin then lymphoid |
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Post transplant lymphoproliferative disorder |
PTLD therapeutic immunosuppression lead to B cell hypertropy and eventual dysplasia will cause symtpoms similar to mono, if mutations occur lymphoma may arrise |
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Phases of post transplant infection |
3 phases, first month, next 6 then after than first is related to surgery or hospital stay, second month are more severe microbes, late are long lasying infections |
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CV disease post transplant |
3-5 times greater major causes of morbidity post transplant are hypertension, CV disease, diabetes, osteoporosis mortality, include coronary artery disease, sepsis, neoplasm |
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Transplant patietns with CHF |
unadjusted long-term survival of renal transplant patients hospitalized for CHF in the Us has improved minimally over the past two decades one year mortalirty with CHF is 24% very high risk need evasive action asap |
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Xenortransplantation |
suggested due to the shortage problems are zoonoses, antigenicity particularly carb ags, xenoreactive natural abs activate complement and coagulation pathways |
