Transplant Flashcards
Immunosuppression combination least likely to cause Post transplant diabetes mellitus
Belatacept, MMF +pred
BPM
What is the frequency of post transplant DM within 1 year post transplant
5- 20%
What are the risk factors for post transplant DM
Age> 40
Family Hx
Obesity
African American
Meds most likely to increase the risk of pTDM are calcineurin inhibitors, mTOR inhibitors + corticosteroids.
Tacrolimus-based regimens are associated with a higher risk of PTDM than cyclosporine. As such, the 2 regimens above that include tacrolimus are not preferred for this patient at increased risk for PTDM. Everolimus and other mTOR inhibitors appear to be powerfully diabetogenic in combination with CNIs but less so when used without CNIs.
MMF + azathioprine have not been shown to have diabetogenic effects.
Simultaneous Liver/ Kidney transplant criteria
Liver transplant candidates who also meet one of the following criteria:
Diagnosis of CKD with a measured or calculated GFR of ≤60 mL/min/1.73 m2 for >90 consecutive days and at least one of the following at the time of waiting list registration:
ESRD on dialysis
Measured or calculated creatinine clearance or GFR ≤35 mL/min/1.73 m2
Diagnosis of sustained AKI and at least one of the following for the last 6 weeks:
Dialysis at least once every 7 days
Measured or calculated creatinine clearance or GFR ≤25 mL/min/1.73 m2 documented at least once every 7 days
Diagnosis of metabolic disease with an additional diagnosis of at least one of the following:
Hyperoxaluria
Atypical hemolytic-uremic syndrome from mutations in factor H or factor I
Familial non-neuropathic systemic amyloidosis
Methylmalonic aciduria
45 yo transplant woman with a hx of ESRD secondary to ADPCKD gross haematuria, low grade fever, nasal congestion + conjunctivitis. Bladder inflammation + interstitial nephritis with viral inclusions
BK virus PCR is negative.
On valtrex
Ans Adenovirus
Usually presents with fever + gross haematuria within the first 3 months post transplant.
Haemorrhagic cystitis is well described.
Histologic features of adenovirus nephropathy are tubular cell necrosis, nuclear enlargement, basophilic nuclear inclusions, and granulomatous tubulointerstitial nephritis
Immunohistochemical stains confirm the presence of adenovirus antigens. Electron microscopy shows adenovirus particles 70–80 nm in diameter within tubular epithelial cells. Features of tubular inflammation may be difficult to distinguish from those of cellular rejection.
Treatment involves IV IG as well as reducing immunosuppresion
What is the cause of hypotension during reaction to ATG?
Ans: Refractory hypotension is most likely related to interleukin- 6 and other pro- inflammatory cytokines, induced by ATG administration.
Cytokine release syndrome (CRS) is a form of systemic inflammatory response that can occur after ATG infusion.
Treatment of CRS-related hypotension consists of volume expansion if tolerated, vasopressors, corticosteroids, and sometimes anticytokine therapy with tocilizumab, an IL-6 receptor targeted monoclonal antibody.
Is more intense immunosuppression associated with BK nephropathy?
BK nephropathy typically presents in the first 1–2 years after transplantation and is more common with more intense immunosuppression
Management of de novo TMA following transplant?
Ans: Discontinue tacrolimus
De novo TMA after kidney transplant has multiple potential etiologies, including CNIs, antibody-mediated rejection (AMR), other immunosuppressants (such as mammalian target of rapamycin [mTOR] inhibitors), viral infections (e.g., CMV), and complement pathway mutations.
How long post malignancy do you have to wait for transplant?
2 years cancer free for prostate cancer
5 years - myeloma, breast cancer + melanoma
What BMI is a contraindication to kidney transplant?
> 40
Whats the most common type of PTLD
Non Hodgkin lymphoma with approx 50% exhibiting extra nodal involvement
PTLD has a bimodal presentation peaking at the first year and then 7- 10 years post transplant
The main risk factors are older age, recipient EBV seronegative status and higher degree of immunosuppresion
Use of belatacept has been assoc with higher risk of PTLD
Treatment for Antibody mediated rejection
IVIG + Plasmapheresis.
Asymptomatic elevation of plasma creatinine 3- 6 months after transplant is concerning for what?
BK nephropathy
Rates as high as 10% have been reported.
“Decoy cells” =
Urine cytology may reveal BK-infected cells, which have been called “decoy” cells because of their resemblance to renal carcinoma cells, but this finding is neither sensitive nor specific.
How do you treat BK nephropathy?
There is no proven strategy to treat BK virus infection.
Recent guidelines recommend reducing immunosuppression.
Kidney biopsy: Acute tubular injury with vacuolisation … “striped pattern”
Think CN inhibitor toxicity
Chronic injury appears as atrophy and fibrosis of the interstitium in a striped pattern (“striped fibrosis”), often with prominent medial hyalinosis of the arterioles
How do you manage tac toxicity?
Reduce first. Dont stop immediately as may cause rejection.
What donor characteristics are important in determining long term graft outcome?
- Donor recipient size match
- Donor age
- HLA match
- Biological first degree relationship of donor + recipient
a kidney transplant froma. younger donor is assoc with a significantly longer expected duration of function
A lower degree of HLA mismatching is assoc. with long term graft survival , although not a lower rate of early rejection
Repeated SCC- what change should you make to immunosuppresive regimen?
Replace tacrolimus with sirolimus
metaanalysis 40% reduction in malignancy overall and 56% reduction in risk of non melanoma skin cancer
But sirolimus = proteinuria, oedema, pneumonitis
?increased risk of death - due to cardiovascular and infection related deaths
What % of patients does membranous nephropathy reoccur in?
10- 45% of patients
and its typically 13- 15 months after transplant
Spontaneous remission of MN is rare after transplant instead early initiation of rituximab is recommended.
Useful measurement in determining whether to pursue dual organ transplant ( liver +kidney)
Hepatic venous pressure gradient.
Patients with HVPG <10 mm Hg are at only 10% risk of developing clinical decompensation in the next 4 years and can safely proceed with kidney transplantation alone
A patient who has elevated HVPG measurements should be considered for a simultaneous liver-kidney transplant, even in the absence of overt clinical signs and symptoms of decompensation.
Most likely complication in transplanted mother
Preterm birth
Up to half of all pregnancies are premature
How long do you advise a woman to wait after transplant before becoming pregnant?
Pregnancy within the first year of transplant clearly increases the risk of graft failure, and this risk may continue into the second transplant year. Consensus guidelines advise that patients who want to become pregnant should wait at least 1–2 years after transplant.
Can you give an blood group A2 kidney to a blood group B recipient with low anti A titres ( 1:4) ?
Yes - blood type A2 have low antigen expression + functionally act similarly to blood group O donors.
As such, blood group B transplant recipients with low anti-A titers can receive a kidney from blood group A2 donors without the need for desensitization or any additional immunosuppression than what is used in ABO-compatible transplantation.
Transplant patient who presents with sepsis, fever, hypotension, confusion, haemorrhagic cellulitis of the legs, mixed acid base disorder following consumption of sea fish
Vibrio vulnificus
T cell lymphomas/ T cell leukaemia in transplant patient - what virus?
Human T- Cell lymphotropic virus - 1
When does FSGS recurr post transplant?
In the initial 12 months
How does steroid withdrawal effect a transplant
Studies have concluded that there is an increased risk of acute rejection early after the transplant but significant declines in subsequent cardiovascular risk; thus, care should be individualized.
35 yo with ESRD due to reflex nephropathy presents with headache + malaise post kidney transpant - plethora, hypertension, Hb: 18, Haematocrit is 54%
What should you do?
Should you do venesection or change immunosuppresion or just recheck in a few months or start enalapril?
Ans: Start enalapril
Post transplant erythrocytosis - presents with a Hb > 17g/dl that developed 6 months after transplant
Incidence of 5- 10%.
More common in male patients who have excellent allograft function without a history of prior rejection. It is also more likely to occur if hx of smoking, did not require ESA prior to transplant. Patients with ADPCKD more likely to get it
RAS of the native kidneys or transplant kidney is also a risk factor.
Typically occurs 8- 24 months after a transplant
Spontaenous remission within 2 years occurs in 25% of patients.
For evaluation - US with doppler study of the native and transplant renal arteries.
For patients with a Hb< 18.5 - then use an ACEi
or ARB
For those > 18.5 - serial phlebotomy is indicated.
Theophylline may be effective as a second line agent.
What is the
Kidney Donor Risk Index
Kidney Disease Profile index
Kidney donor risk index is based on a variety of factors, including age, ethnicity, creatinine, hypertension, cause of death, donor size, hep C + whether the donation occurs after cardiac death
Kidney disease profile index is defined as the percentage of donors in a reference population that has a low risk index
Kidney disease profile index & avg graft srvival
0- 20% 11.44
21- 85% 8.9
86- 100% 5.6
Treatment for CMV pneumonia in a transplant
IV ganciclovir.
Highest risk if transplant from seropositive donor (D+R-), Highest risk from CM is during the first few months after transplant, while receiving treatment for rejection or stopping prophylaxis.
Note that CMV PCR can be negative in the face of tissue-invasive disease; therefore, bronchoscopy is warranted both for the diagnosis of CMV and to exclude other pathogens that can have similar presentations.
Note: Oral valganciclovir is a prodrug of ganciclovir w good oral bioavailability
Can use valganciclovir for mild or moderate CMV disease.
Aciclovir does not reliably treat CMV disease
Fever, cough, hypoxaemia, pulmonary opacities in a transplant
CMV pneumonia.
How do you treat cryptococcal meningitis in a transplant patient?
Liposomal amphotericin B + flucytosine.
For at least 2 weeks, followed by maintenance and then consolidation therapy
Liposomal amphotericin B and amphotericin B lipid complex appear to be equally effective, and either could be combined with flucytosine to treat severe disease. Flucytosine (5-FC) in concert with amphotericin B decreases the rate of treatment failure.
However, the lack of flucytosine has been shown to be a risk factor for treatment failure at 2 weeks; thus, treatment with amphotericin B lipid complex alone would not be the best answer.
Limits RNA + DNA syntehsis
Fluconazole is used as consolidation therapy ( AFTER THE ABOVE) at high doses for 8 weeks and then for maintenance lasting 6- 12 months
Does additional screening have to be done for a sibling in their 30s ( brother with ESRD due to diabetic nephropathy)
Yes - Do OGTT and “computation of insulin secretion/ resistance index”
What are the risks for post donation pregnancies?
Lower rate of full term delivery.
Higher rate of fetal loss, gestational diabetes, HTN proteinuria + preeclampsia
Whats the increased risk of ESRD after kidney transplant?
Increases 8 fold.
But still small - only 1 in 400
