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Allograft
transplant with non-identical individuals
failure, 10, lower, higher, dialysis, lower
Kidney Donor Profile Index (KDPI)
Estimates the potential risk of graft ________ after kidney transplant based on __ donor factors
The _______ the score, the higher the rate of survival
Ranges from 0-100%
Donated kidneys with score <20% → patients with _______ potential for survival
Donated kidneys with score >85% → patients who will fare worse on _________ and need the benefit of transplant earlier, despite receiving potentially _____ quality organ
Hope Act
allows for organ donation from HIV (+) donors
yes
Can kidneys be used from donors after a cardiac death?
pericarditis, seizures, bleeding, diuretics, HTN, metabolic, malnutrition
Indications for Renal Replacement Therapy (transplant and/or dialysis)
______________ or pleuritis (urgent indication)
Progressive uremic encephalopathy or neuropathy
_________ (urgent indication)
Clinically significant _________ diathesis attributable to uremia (urgent indication)
Fluid overload refractory to __________
___ poorly responsive to meds
Persistent __________ disturbances refractory to medical therapy
Persistent nausea and vomiting
Evidence of _________
irreversible, CKD, dialysis, living, 30
Indications for Renal Transplant
_____________ ESRD requiring renal replacement therapy
Late ___ approaching need for renal replacement therapy
Ideally the transplant should take place before ________ is required (pre-emptive transplant, requires _______ donor)
Refer for initial eval with GFR < __ mL/min
2, malignancy, psychosocial, substance, immunologic, age
Absolute Contraindications for Renal Transplant
Chronic illness that limits predicted survival < _ years
Active glomerulonephritis
Active ___________
Active infection
_____________ issues affecting adherence to medical care
Active _________ abuse
_____________ causes
___ is not an contraindication, majority on waitlist > 65 years old
psychiatric, non-compliance, myeloma
Relative Contraindications for Renal Transplant
Severe ____________ disease
Moderately severe degrees of comorbidity
___-__________ with dialysis or other medical therapy
Primary renal diseases
Primary focal sclerosis with prior recurrence in transplant
Multiple ________
Amyloidosis
Oxalosis
antibodies, hyperacute, ABO, HLA, removal
Immunologic Contraindications
presence of preformed __________ against the donor kidney at the time of anticipated transplant → __________ rejection
Natural antibodies against ___ blood group antigens
Natural antibodies against ___ class I or II
Screening for this occurs routinely early in process
________ of antibodies directed at donor tissue now routinely performed with varying success
single, 6, target, polymorphic
Organ Selection - HLA Compatibility
Match HLA major histocompatibility
Each mammalian species has a _______ chromosomal region that encodes the major histocompatibility antigens, this region on human chromosome _ codes the HLA genes
HLA can be immunologic _______ of organ rejection due to its highly ____________ properties
etiology, recurrence, familial, transplants, immunosuppressive, hypercoagulable
Recipient Evaluation → History: thorough medical and surgical history
_________ of original kidney disease and risk of __________ with the transplanted kidney
History of __________ or hereditary kidney disease, particularly if living, related donation is an option
Potential sensitization risks, including history of blood or platelet transfusion, pregnancies, and previous ___________
History of prior ________________ therapy
History of _______________ state
Medical co-morbidities: DM, CAD, CV disease, HTN
abdominal, P450, immunization, cause, complications
Recipient Evaluation → History: thorough medical and surgical history
History of prior surgery, especially _____________
Review of meds, especially those metabolized by cytochrome ____ system
___________ history
Physical activity history to assess functional status
In retra-transplantation candidates, prior transplantation courses and _____ of graft loss, medication adherence, and previous transplant ________________
BMI, infection, carotid, femoral, pedal, masses, dialysis
Recipient Evaluation → Physical: detailed physical exam
Assessment of ___ and central adiposity
Oral exam looking for advanced dental decay and signs of _________
Auscultation for ________ bruits
Assessment of bilateral _________ and ______ pulses and lower extremity integrity
Palpation for abdominal ______ and assessment of prior abdominal procedure that may affect placement of the kidney transplant
___________ access location (in those receiving it)
CMV, simplex, varicella, EBV, B, C, syphilis
Recipient Evaluation → Serologic Tests
Cytomegalovirus (___)
Herpes ________ virus
___________-zoster virus
Epstein Barr virus (___)
HIV
Hep _ and _ viruses
Treponemia pallidum (__________)
MMR
PPD, gamma, TB
Recipient Evaluation → Non-serologic Tests
___ or interferon-_____ release assay for __
CXR
stress, CT, carotid
Recipient Evaluation → Cardiovascular Testing
EKG
Echocardiogram
_______ Test
__ abdomen/pelvis: evaluate vasculature
_______ dopplers
smoking, lung
Recipient Evaluation → Pulmonary Function Testing
If significant __________ history
If chronic ____ disease
adherence, social worker, neuropsychiatric
Recipient Evaluation → Psychosocial Assessment
Identify behavioral, social, and/or financial issues that may influence ________ and outcomes after transplant
Performed by ________ _______ or psychologist trained in evaluation of transplant candidates
Potential further eval with referral for ______________ assessment
immunosuppressive, cognitive, psychiatry, substance
Recipient Evaluation → Psychosocial Assessment
Understanding of potential risks and benefits of transplant need for lifelong ________________ therapy, and need for adherence to medication regimen
___________ evaluation for decision-making capacity and ability to give informed consent
Patients with mental health issues need to establish care with _____________ to improve access and success after surgery
Patients with __________ abuse disorders
including alcohol, tobacco, recreational drugs
different centers have different contraindications but patient needs to be substance-free for certain period of time
contraindication, financial, insurance
Recipient Evaluation → Psychosocial Assessment
Social support system in place, lack can be considered a _________________
____________ support given the high costs of immunosuppressive therapy and potential ____________ issues; make sure transplant and follow-up care is feasible
0, 3
Frailty Evaluation
Assesses fatigue, resistance, ambulation, illness, and loss of weight
Score _+ = frail
Score _ = healthy
laparoscopic, living, robotic
The Surgery Process → Donor Kidney
________________ or open abdominal surgery
Laparoscopic most common in ________ donors
_________ becoming more common
hemodialysis, 48, potassium, arrhythmias
The Surgery Process → Kidney Recipient
Adequate ______________ should be performed within __ hours prior to surgery as needed to control serum ___________ to prevent cardiac _________
open, iliac fossa, renal, external iliac, renal, external iliac, mucosa, 2
The Surgery Process
Recipient: _____ abdominal surgery
Kidney allograft is placed in recipient’s ________ ______ using retroperitoneal approach
Anastomosis is made between donor ______ artery and recipient __________ ________ artery and donor ______ vein to recipient ________ _______ vein
Anastomosis of donor ureter to the recipient bladder ________
The kidney allograft starts to produce urine immediately after anastomosis
Serum Cr should start to fall as allograft starts functioning, typically within _ weeks (can be as longa s 6 weeks though)
ischemia, diuresis, sodium, potassium, water, biopsy
The Surgery Process → Initial Issues
Some degree of acute tubular injury due to ________ → Post-operative _________
Large amounts of ________, ___________, and ______ may be lost post-op, requires close monitoring
If slow urine recovery → allograft ________
immunosuppressive, steroids, antimetabolites
The Surgery Process
_____________________ therapy, maintenance _________, and _____________ start on day of surgery
corticosteroids, thymoglobulins, IL2
The Surgery Process → Induction Meds
_______________
_______________
___ receptor antagonists (Basilizimab, Daclizumab)
corticosteroids, calcineurin, metabolites, mTOR
The Surgery Process → Maintenance Meds
______________
________________ inhibitors (cyclosporine, tacrolimus)
Anti____________ (Azathioprine, MMF)
____ inhibitors (sirolimus, everolimus)
function, irreversible, swelling, creatinine, volume
Management of Rejection
Early diagnosis of rejection → preserving allograft _________ and preventing lasting _____________ damage
Rarely shown in patient with fever, _________, and tenderness over surgery site
Frequently shows as a bump in serum __________ ± reduction in urine _______
ultrasound, vascular, obstruction, biopsy, T, antibody
Management of Rejection
Doppler __________: shows allograft vascular changes, urinary ___________, or presence of perirenal urine collections, blood or lymph
Allograft ________: gold standard for diagnosis of _ cell mediated and __________ mediated rejection
T, infiltration, steroids, antibody
Management of Rejection
_ cell mediated rejection
Presence of immune cell ___________ in the interstitial, tubular, or vascular compartments
Treatment: IV high-dose _________
If inadequate response to steroid → need to start __________ therapy
antibody, endothelial, complement, antibody, plasmapheresis, B, plasma
Management of Rejection
____________ mediated rejection
____________ injury and deposition of ___________ component C4d is detected in peritubular capillaries
Detection of circulating donor-specific _________ in recipient’s blood
Treatment
_____________
IVIG
Anti-CD20 monoclonal antibody to target _ lymphocytes (rituximab)
Bortezomib to target antibody-producing _______ cells
MI, steroid, CAD, age
Complications
Increased incidence of death from __ and stroke
Worse risk in DM patients, high _______ use in immunosuppression
High prevalence of ___ and PVD
Worsening with increased numbers of DM patients and increased average ___ of recipients
hypertension, native, stenosis, CCB, 120-130, 70-80
Complications
_____________:
________ kidney disease
Rejection of transplant
Renal artery _________
Renal CNI toxicity
Treatment: ___ have been shown to reduce long-term mortality
Goal Range: ___-___/__-__ mmHg
cultures, viral, US, reduction
Complications
Opportunistic Infections
Blood, urine, drain fluid __________
______ load in plasma
Imaging: __ and CT
Goals
Adequate source control
Anti-microorganism therapy
_________ of immunosuppression
immunosuppressive, skin, lips, lymphoproliferative, EBV, reduction, chemotherapy, rejection
Complications → Malignancy
5-6% increase in incidence to tumors due to ___________ therapy
Cancer of ____ and ____ are most common
Post-transplant __________________ disease within first year or around years 7-10 has increased risk with solid organ transplants
Associated with ___, poor prognosis
Treatment
_________ of immunosuppression
Surgery
Conventional _____________
Radiotherapy
Cancer immunotherapy → 30-40% increased risk of allograft __________
1, antibody, HTN, CCB
Complications → Chronic lesions of transplanted kidney
Chronic renal transplant dysfunction, typically starting _ year post-transplant
Chronic active _________-mediated rejection
Recurrent glomerular disease
___
CNI nephrotoxicity
Secondary focal glomerulosclerosis
Combination of these pathophysiologies
Control of systemic and intrarenal hypertension with ___ has been shown to slow rate of progression of dysfunction
parathyroid, parathyroidectomy, phosphorus
Complications → Hypercalcemia
Potential indication of failure of hyperplastic __________ glands to regress
May require subtotal _______________
Incidence has improved with better management of calcium and __________ metabolism during chronic dialysis
bone marrow, steroids, B, B, HCV
Complications
Anemia
____ _______-suppressant meds
GI bleeding from long-term high dose ________
Chronic Hepatitis
Hep _, higher risk if previously Hep _ surface antigen (+)
Due to immunosuppression
Direct-acting ___ antiviral meds have reduced this risk