Transplant Flashcards
Diseases that can recur post-transplant?
Highest recurrence rates:
- Primary FSGS
- C3GN, DDD
- Atypical HUS
- IgA
- Membranous
- Others:
- Diabetic nephropathy
- Primary Oxalosis if liver not transplanted
Transplant recipient contraindications?
- Recent or metastatic cancer
- Untreated current infection
- Severe irreversible extrarenal disease
- Recalcitrant treatment nonadherence
- Psychiatric illness impairing consent and adherence
- Current recreational drug abuse
- Aggressive recurrent native kidney disease - ???
- Limited, irreversible rehabilitative potential
- Primary oxalosis
- Uncorrectable chronic hypotension
Contraindications to deceased donation?
- Most cancers
- Apart from non-melanoma skin cancer or small RCC that can be resected at time of transplant, most are contraindicated
- Certain infections
- Severe, multifocal, difficult to treat
- Active HIV
- Severe fungal
- Viral - Measles, adenovirus
- Prion disease
Banff criteria for acute antibody-mediated rejection?
Need all of:
- No AMR chronicity criteria met
- AMR activity criteria (any of):
- g >0
- ptc >0
- v >0
- Acute TMA in the absence of other cause
- ATN in the absence of other cause
-
Antibody interaction with tissue (any of):
- +C4d
- g+ptc >=2
- increased expression of validated gene transcripts/classifiers in biopsy tissue strongly correlated with AMR
- +DSA
What is exceptional distribution?
= “increased risk distribution”. NOT about kidney quality and more about social history/med history of donor.
- Unknown travel history, ?TB ?Zika
- Remote history of low risk cancer
- Infection that can be treated
- High risk sexual or substance use behavior
- MSM
- IVDU
- Sex worker
- Jail
- Lived somewhere with high risk of infections
- Neurodegenerative disease
What is expanded criteria (ECD)?
- Age >= 60 or
- Age >= 50 and 2 out of 3 of:
- HTN
- Death from stroke
- Cr >132
Transplant list exceptions/prioritization criteria?
- Pediatric (growth retardation)
- Medical emergency
- Uremic cardiomyopathy
- Lack of vascular access
- 2 organs needed
- HLA 6/6 match (too good of a match)
- PRA>95%
- If a living donor gets ESRD
Treatment of ABMR?
- IVIG
- PLEX if +DSA
- Rituximab
- Steroids
- +/- eculizumab
What features make BKVN more likely (vs. ABMR)?
- BK viremia >10,000 copies
- +SV40
- Intranuclear viral inclusions in renal tubular nuclei
- Decoy cells in urine
- More likely medullary inflammation as opposed to cortex
- Ureteral stenosis
How does BKVN usually present?
Asymptomatic rise in creatinine during the 1st year post-transplant
Biopsy findings for diagnosis of BKVN?
- Allograft biopsy shows BK viral inclusions in renal tubular nuclei and glomerular parietal epithelium. Intersititial mononuclear inflammation (plasma cell-rich), focal tubulitis. SV40 positive.
Treatment algorithm/options for BKVN?
- Reduce CNI
- Reduce anti-metabolite
- Reduce both CNI and anti-metabolite
- Change tac to cyclosporine or sirolimus
- Switch MMF to AZA or leflunomide
- Other alternatives: cidofovir, quinolone, IVIG
Renal allocation system considerations
- Prioritization – multiple organ, children, medical urgency
- Age matching
- Waiting time
- Sharing within national registry
- Seek to avoid wasting organs
- Not be based on patients’ residence
- Testing to prevent the spread of infectious diseases
- Reduce inequalities from SES
CMV prophylaxis - when and how long?
- Donor - / Recipient – No treatment
- Donor + / Recipient – Valganciclovir x 6mos (CMV mismatch)
- Donor - / Recipient + Valganciclovir x 3 months (If induction with thymoglobulin x 6mos)
- Donor + / Recipient + Valganciclovir x 3 months (If induction with thymoglobulin x 6mos)
Immediate and long-term complications of living kidney donation
- Immediate complications
- Surgical complications – Pain, bleeding, infection, risk of laceration to another organ, PE/DVT, hospital-acquired illnesses
- Time away from work, financial loss
- Psychosocial – fear, anxiety, depression
- Longterm complications
- Increased risk of proteinuria
- Increased risk of HTN
- No effect on fertility or outcome of future pregnancies (preterm delivery or low birth weight), but greater incidence of pre-eclampsia (11% in donors compared to 5% in matched no-donors). Therefore, advisable to delay pregnancy for up to at least 6 months to allow for maximal compensatory hypertrophy of the single kidney.
Causes of anemia post-transplant (pharmacological and non-pharmacological)
- Pharmacological
- Immunosuppression: MMF, AZA, sirolimus, everolimus
- Septra
- Dapsone (hemolytic anemia)
- Discontinuation of EPO therapy
- Non-pharmacological
- Post-op bleeding
- Iron deficiency
- Infection eg. parvovirus
- Tertiary hyperparathyroidism
- Occult GIB
Causes of graft loss after 1 year?
- Chronic antibody rejection
- CNI toxicity
- Native disease recurrence
- BK nephropathy
3 antigen-presenting cells
- Macrophages
- Dendritic
- B lymphocytes
Pathologic features of chronic CNI toxicity
- arteriolar hyalinosis, then progresses to obliterative arteriolopathy (suggesting primary endothelial damage) – both afferent and efferent arterioles are affected as compared with diabetes having usually only afferent hyalinosis
- ischemic collapse or scarring of the glomeruli,
- vacuolization of the tubules,
- global and focal segmental glomerulosclerosis,
- focal areas of IFTA (producing a picture of “striped” fibrosis).
How do CNI’s cause nephrotoxicity
- Renal vasoconstriction / afferent arteriole
- Interstitial fibrosis
- TMA
Risk factors for developing diabetes post-transplant
- Obesity (RR 1.7)
- Older age >60 (RR 2.6)
- Black/Hispanic (RR 1.7)
- Hep C (RR 1.3)
- Immunosuppression with steroids, CNI (Tac RR 1.3), sirolimus
MMF in pregnancy?
- Black box warning: number of reports of 1st trimester pregnancy loss and congenital fetal abnormalities (face and ear).
- Stop months before attempting conception. Must be off minimum 6 weeks (washout period), but usually 3 months to ensure new immunosuppressive regimen stable.
What immunosuppression meds are safe and not safe in pregnancy?
Safe: prednisone (note: high dose a/w cleft lip), CNI, azathioprine
Not safe: MMR, sirolmius, belatacept
What criteria to consider to decrease risk of pregnancy in transplant recipents?
- >1 year post-transplant
- Serum Cr <133
- No recent episodes of acute rejection
- Normotensive or minimal antihypertensive regimen
- Minimal or no proteinuria (<500 mg/day)
- Normal allograft ultrasound
- Pregnancy-safe drug regimen
Active CMV infection vs. CMV disease?
- Active CMV infection – CMV viremia (with or without symptoms) (~5000)
- CMV disease – CMV viremia + clinical manifestations of CMV disease (CMV syndrome OR tissue-invasive CMV disease)
- CMV syndrome – CMV viremia + attributable symptoms/signs (fever, arthralgia, leukopenia, thrombocytopenia, etc.)
- Tissue-invasive CMV disease – End-organ disease (eg. enteritis, colitis, hepatitis, nephritis, pneumonitis, meningitis, encephalitis, retinitis)
When to treat CMV in transplant, how, and how long?
- Management:
- Active CMV infection – Stop antimetabolite, monitor PCR. If continued replication, start antiviral.
- CMV disease
- Stop antimetabolite
- Start antivirals
- IV ganciclovir 5mg/kg q12h for severe disease, or
- Oral valganciclovir 900 mg bid (adjust for kidney fxn)
- CMV PCR weekly x 4 weeks
- Duration of treatment: Usually 3 weeks. Treat until no CMV viremia in 2 PCRs, 1 wk apart. May be longer for more severe disease.
- Secondary prophylaxis for 1-3 months (valgan 900 mg daily)
HLA desensitization protocol?
- IVIG (immunomodulation of recipient)
- Rituximab (deplete B cells responsiblefor anti-HLA antibody production)
- PLEX (removal of anti-HLA antibodies)
Window period for HIV, Hep C, HepB in the setting of exceptional distribution?
For NAT testing:
HIV - 5-6 days
Hep C - 3-5 days
Hep B - 20-22 days
Transplant tourism cons?
- Compared to local donation, increased risk of infections
- Increased risk of graft loss
- Increased risk of mortality
- Increased risk of adverse outcomes for living donor and unethical
Pros/cons of basiliximab vs. ATG
- Basilximab (IL-2 antibody)
- Lower risk of opportunistic infection and malignancy
- Use if rabbit allergy
- ATG
- Decreased risk of DGF
- Use for highly sensitized
Cytotoxic vs. Flow cytometry cross-match?
- Cytotoxic: Recipent serum + Donor lymphocytes + Complement
- Cell lysis if positive
- Specific but not sensitive
- Flow: Recipient serum + Donor lymphocytes + Fluroscent antibodies that binds al human IgG
- Run through machine to see signal strength
- Sensitive
T and B cell cross-match interpretation:
T cell neg, B cell neg
T cell pos, B cell neg
T cell neg, B cell pos
T cell pos, B cell pos
T cell neg, B cell neg - NEGATIVE XMatch
T cell pos, B cell neg - POSITIVE Class I
T cell neg, B cell pos - POSITIVE Class II antibodies
T cell pos, B cell pos - POSITIVE Class I and II
(T cells express Class I, B cells express both Class I and II)