Renal transplant Flashcards
CMV infection
CMV IgM positive antibodies, 4x increase in pre existing CMV IgG titers
CMV antigen detection infected cells,
CMV DNAemia in blood
Viral isolation by throat culture, buffy coat or urine tests
CMV disease
clinical signs of fevers and leukopenia,
organ involvement: hepatitis, pneumonitis, pancreatitis, colitis, meningoencephalitis, chorioretinitis and myocarditis
What are symptoms of CMV disease
see mononucleosis like disease with clinical low grade fever, malaise, leukopenia and some degree of organ involvement
Difference between CMV infection vs CMV dx
CMV infection is detection of CMV antigen, antibodies or virus without significant clinical symptoms whereas CMV dx is clinical symptoms
CMV eye dx is seen in (name population of pt)
HIV more than organ transplant pt
CMV dx is more common in (name pt population)
CMV positive donors and CMV positive recipients
CMV dx often happens after
renal rejection episode and increased immunosuppression
Pt can reactivation of CMV virus or superinfection after
introduction with a new donor viral strain
Prophylaxis after having positive CMV in donor or recipient
100 days of ganciclovir
Treatment of CMV dx
reduction in immunosuppression
OR if severe dx can give ganciclovir
Only stop cyclosporine or tacrolimus if lifethreatening dx
BK virus infection presentation
tubulointerstitial nephritis and ureteric stenosis
How to follow BK virus in patients?
Check BK PCR or acute organ dysfunction
Kidney biopsy - BK involvement
HSV reactivation happens when after a renal transplant?
1st few months after solid organ transplant
HSV reactivation presentation in tranplant pt
oral genital lesions, esophagitis, pneumonitis, hepatitis, and encephalitis
Tacrolimus toxicity presentation
acute nephrotoxicity, HTN, neurotoxicity (tremor), metabolic disturbances (high blood sugars)
Toxoplasma gondii infection presentation
rarely happens: see lymphadenopathy, hepatosplenomegaly, pneumonitis, myocarditis, brain abscess, chorioretinitis
human polyoma virus infection
high prevalence of seropositivity of polyoma virus (BK or JC) in general population but they only cause dx in immunocompromised pts
BK virus (polyoma virus) manifestations in a renal transplant patinet
tubulointerstitial nephritis and uretic stenosis
time to onset of BK infection post transplant
10-15 months
seen in older men with DM2 and rejection episodes
clinical manifestations of BK virus infection in renal transplant pt
no characteristic clinical manifestations other than loss of renal function.
treatment of BK virus
primary treatment is reduction of immunosuppression.
diagnosis of BK virus in transplant pt
Renal biopsy is similar to CMV and most people will have antibodies to BK virus.
Diagnosis is via characteristic cytopathology + positive antibodies against BK on immunohistorchemistry tests.
what can you see on urine cytology with BK virus
can see cells with single large basophilic intranuclear inclusion
- suggests BK virus but doesn’t prove it.
typical infections in 1st month post transplant
similar to post operative pts
Aspiration (pseudomonas) line infection (MRSA) wound infection and c diff.
Rarely: Ols, infections due to donar allograft contamination HIV, histoplasma, rabies or recipient colonization of aspergillosus)
1-6 months post transplant infections
with PCP/antiviral prophylaxis - viral BK polyoma, hep C, adenovirus, influenza, - bacterial C diff colitis and TB WITHOUT PCP and antiviral prophylaxis (in addition to above) - Viral: CMV, HSV, VZV, EBV, hep B fungal: PCP bacterial listeria, nocardia parasitic: strongyloides, toxoplasma
> 6 months post transplant
similar to general population less commonly late viral: CMV, HSV, JCV, hepatitis B and C bacterial nocardia and rhodococcus fungal: aspergillus, mucor
what causes acute transplant rejection
presents early after surgery or within 6 months due to non compliance or over aggressive reduction in immunosuppression.
asymptomatic but also can have graft pain and tenderness, fever, hypertension, oliguria, acute renal failure, pyuria, and proteinuria and increased graft size on imaging
signs and symptoms of acute transplant rejection of kidney
BK virus infection happens
1 year after transplant
see rising Cr, abnormal urinalysis with proteinuria and hematuria and casts and see tubulointerstitial nephritis
BK virus infection
hypertensive nephrosclerosis is seen with
longstanding history of uncontrolled HTN and see slowly rising cr and mild protineuria
does lupus nephritis recur in transplant pts?
yes up to 10% of transplant kidneys get this.
see increased Cr, new proteinuria and hematuria
What can cause an acute increase in tacrolimus or cyclosporine concentration in someone who uses them for immunosuppression for renal transplant?
tacrolimus and cyclosporine are metabolized by the hepatic cytochrome P450 system and excreted bin bile.
So any drugs that interact with P450 can increase or alter drug level and effect.
Lansoprazole and grapefruit juice can increase drug levels of tracrolimus
tacrolimus toxicity:
see nephrotoxicity with acute rise in serum Cr, tubular dysfunction and bland urinlaysis
Can see hypertension, neurotoxicity with tremor, headache, visual difficulties,
see metabolic changes (hyperglycemia, hyperkalemia, hypomagnesemia)
what drugs can increase tacrolimus and cyclosporine levels?
antibiotics like macrolides antifungals (itraconazole) cardiac (ACEi and CCB) GI drugs (Lansoprazole) Dietary :grapefruit juice
these can increase concentrations and cause toxicity of these immunosuprressive drugs
need to get a drug level and adjust it
common drug interactions that can lower the levels of tacrolimus and cyclosporines
antibiotics (nafcillin, rifabutin)
antiseizure (carbamazepine, phenytoin
other (octreotide, St. John’s wort, orilstat)
what are the most common side effects of tacrolimus and cyclosporine toxicity ? (Too much of it)
renal: most common side effect with acute renal failure and bland UA
Vascular: HTN
Neurotoxicity: tremor, headache, visual difficulties
Metabolic: hyperglycemia, hyperkalemia, hypomagnesemia
Infection: increased risk
malignancy: cutaneous squamous cell cancer and lymphoproliferative disorders
do tacrolimus and cyclosporine increase risk for cancer?
yes with cutaneous squamous cell cancer
lymphoproliferative disorders.
for someone who has worsening kidney function and AKI with electrolyte abnormalities in a renal transplant what to do?
biopsy is often done to rue out acute rejection; look for histological findings (interstitial inflammation, intimal inflammation tubulitis) are non specific
calcineurin inhibitor toxicity is suggested with absence of signs of acute rejection
tacrolimus toxicity facts
is it dose dependent?
is it reversible?
on dose; dose dependent
treatment is with decreasing dose and generally reversible. some pts can have a chronic renal dysfunction.
Treat calcineurin induced hypertension with hyperkalemia with:
thiazide diuretics.
renal transplant pts who want to get pregnant need to:
need to wait 1-2 years with stable allograft before attemtping conception
also need to stop mycophenoalte mofetil and sirolimus and everolimus because teratogenic.
needs to be replaced by azathioprine which is safer in pregnancy.
