Transplant

Question 1

Immunosuppression combination least likely to cause Post transplant diabetes mellitus

Answer 1

Belatacept, MMF +pred

BPM

Question 2

What is the frequency of post transplant DM within 1 year post transplant

Answer 2

5- 20%

Question 3

What are the risk factors for post transplant DM

Answer 3

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.

Question 4

Simultaneous Liver/ Kidney transplant criteria

Answer 4

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

Question 5

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

Answer 5

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

Question 6

What is the cause of hypotension during reaction to ATG?

Answer 6

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.

Question 7

Is more intense immunosuppression associated with BK nephropathy?

Answer 7

BK nephropathy typically presents in the first 1–2 years after transplantation and is more common with more intense immunosuppression

Question 8

Management of de novo TMA following transplant?

Answer 8

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.

Question 9

How long post malignancy do you have to wait for transplant?

Answer 9

2 years cancer free for prostate cancer

5 years - myeloma, breast cancer + melanoma

Question 10

What BMI is a contraindication to kidney transplant?

Answer 10

> 40

Question 11

Whats the most common type of PTLD

Answer 11

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

Question 12

Treatment for Antibody mediated rejection

Answer 12

IVIG + Plasmapheresis.

Question 13

Asymptomatic elevation of plasma creatinine 3- 6 months after transplant is concerning for what?

Answer 13

BK nephropathy

Rates as high as 10% have been reported.

Question 14

“Decoy cells” =

Answer 14

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.

Question 15

How do you treat BK nephropathy?

Answer 15

There is no proven strategy to treat BK virus infection.

Recent guidelines recommend reducing immunosuppression.

Question 16

Kidney biopsy: Acute tubular injury with vacuolisation … “striped pattern”

Answer 16

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

Question 17

How do you manage tac toxicity?

Answer 17

Reduce first. Dont stop immediately as may cause rejection.

Question 18

What donor characteristics are important in determining long term graft outcome?

Answer 18

• 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

Question 19

Repeated SCC- what change should you make to immunosuppresive regimen?

Answer 19

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

Question 20

What % of patients does membranous nephropathy reoccur in?

Answer 20

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.

Question 21

Useful measurement in determining whether to pursue dual organ transplant ( liver +kidney)

Answer 21

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.

Question 22

Most likely complication in transplanted mother

Answer 22

Preterm birth

Up to half of all pregnancies are premature

Question 23

How long do you advise a woman to wait after transplant before becoming pregnant?

Answer 23

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.

Question 24

Can you give an blood group A2 kidney to a blood group B recipient with low anti A titres ( 1:4) ?

Answer 24

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.

Question 25

Transplant patient who presents with sepsis, fever, hypotension, confusion, haemorrhagic cellulitis of the legs, mixed acid base disorder following consumption of sea fish

Answer 25

Vibrio vulnificus

Question 26

T cell lymphomas/ T cell leukaemia in transplant patient - what virus?

Answer 26

Human T- Cell lymphotropic virus - 1

Question 27

When does FSGS recurr post transplant?

Answer 27

In the initial 12 months

Question 28

How does steroid withdrawal effect a transplant

Answer 28

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.

Question 29

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?

Answer 29

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.

Question 30

What is the

Kidney Donor Risk Index

Kidney Disease Profile index

Answer 30

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

Question 31

Treatment for CMV pneumonia in a transplant

Answer 31

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

Question 32

Fever, cough, hypoxaemia, pulmonary opacities in a transplant

Answer 32

CMV pneumonia.

Question 33

How do you treat cryptococcal meningitis in a transplant patient?

Answer 33

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

Question 34

Does additional screening have to be done for a sibling in their 30s ( brother with ESRD due to diabetic nephropathy)

Answer 34

Yes - Do OGTT and “computation of insulin secretion/ resistance index”

Question 35

What are the risks for post donation pregnancies?

Answer 35

Lower rate of full term delivery.

Higher rate of fetal loss, gestational diabetes, HTN proteinuria + preeclampsia

Question 36

Whats the increased risk of ESRD after kidney transplant?

Answer 36

Increases 8 fold.

But still small - only 1 in 400