PHRM 542 Solid Organ Transplant Rejection

When does acute kidney transplant rejection most commonly occur?

Within the first 12 months

What are physical exam findings of acute kidney transplant rejection?

Worsening HTN

What are laboratory findings associated with acute kidney transplant rejection?

New increase in SCr ≥ 25% from baseline or higher than expected

Proteinuria > 1 g/d

Plasma donor-derived cell-free DNA > 1%

Describe BK virus in renal transplant

Highly prevalent polyoma virus that causes lifelong latent infection in the renal tubular and uroepithelial cells

What are risk factors for BKNV (nephropathy)?

Intensity of immunosuppression

HLA or ABO mismatched transplant

Describe the general treatment of acute T-Cell mediated rejection (TCMR)

Check patient adherence

Check trough tacrolimus levels

Add prednisone 5 mg/day if patient was steroid-free

Monitor SCr daily until response then weekly

What agents are used to treat TCMR?

rATG

Alemtuzumab

How should alemtuzumab doses be monitored?

Monitor for at least 2 hours after dose for CRS

May be fatal

When should antimicrobial and antiviral prophylaxis be used for patients in TCMR?

In ALL patients treated with rATG or alemtuzumab/high-dose steroids for TCMR

Administer for 3 months

How is ABMR diagnosed?

Histology on biopsy

C4d staining

Serologic evidence of circulating donor-specific antibodies

What is the goal when treating ABMR?

Remove existing DSAs and to eradicate the clonal population of B cells or plasma cells responsible for their production

How is ABMR treated?

Plasmapheresis and IVIG if C4d positive and/or DSA positive

Methylprednisolone 500 mg IV/day x 3 days followed by rapid prednisone taper

How long is plasmapheresis and immunoadsorption performed for ABMR?

Daily or every other day for 3-7 sessions or until the SCr is within 20-30% of baseline

What IVIG solutions are preferred?

No more than 5% concentrated to decrease the risk of AKI

What should be done before administration of IVIG?

Prehydration to avoid thrombotic and renal complications

Signed consent

What could be added to IVIG therapy in ABMR to inhibit production of DSAs?

Rituximab or bortezomib

What are early ADEs of IVIG?

RATE-RELATED

Anaphylactoid, flu-like symptoms, thrombosis

What are delayed ADEs of IVIG?

IG-induced AKI

Thrombosis

Aseptic meningitis

HA/migraine

PRES

What are BBWs of IVIG?

IG-induced AKI

Thrombosis

Describe the metabolism of bortezomib

MAJOR substrate of CYP2C19 and CYP3A4

P-gp substrate

When should administration of bortezomib be avoided?

Avoid administration with strong CYP3A4 inducers

When should bortezomib be dose reduced?

Dose reduce if administered with strong CYP3A4 inhibitors