Q.686. Comment briefly on CMV infection in R.Tx.?
KIDNEY TRANSPLANT AND INFECTION
Q.686. Comment briefly on
CMV infection in R.Tx.?
A. CMV
increase é age, more than 2/3rds of recipient have Ig. G
+ve, .. Sources:
Reactivation of latent virus. or,
Iry infection é donor-derived virus é allog. or blood
products. or,
Reactivation
of latent donor virus.
-
CMV. disease 🠞= [Infection + Sm.s or tissue invasion].
-
Risk is
highest é : 🠞+D/-R then,
+D/+R then, -D/+R then, –D/-R.
-
OKT3 & thymoglobulin 🠞🠝risk of subsequent disease arises 1-6 m. post Tx.,
but Retina & G.I. 🠞🠝6 m.
-
C. P.🠞[fever- malaise-leukopenia]. (see Q.
22).
-
Detection of CMV é blood, tissue fluid, best achieved by specfic Ag. assay, PCR, and in tissue by immunohistochemistry.
-
* ttt.: (1) Reduce im/m. dose.
(2) I.V. Gancyclovir/2-4 w, foll. by oral
antiviral/2-3
m. – Valgancyclovir: 🠊much better absorbed (P.O) than gancyclovir.
* Prox. : P.O. Valgancyclovir & Gancyclovir.
“CMV Terminology”.
CMV infection:
{Isolation of CMV virus or detection of viral proteins or nucleic
a. in any body fluid or tissue specimen}.
Viremia: [CMV isolation by
culture by using standard or shell
vial techniques].
Antigenemia:
[Detection of CMV pp 65 in leukocytes].
Primary CMV
infection: [Detection of CMV infc. in previously CMV
sero-ve].
Recurrent infc.:
[New detection of CMV
infc. in previously documented infc. ptn.
who hs not hd virus detected for interval of at least 4 w. e active surveillance].
Reinfection: [Detection
of a CMV strain that is distinct from the strain that was the cause of the
patient’s original infection].
CMV GI. dis.:[Combination of Sms
from upper/lower GIT, findings of macroscopic mucosal lesions
on endoscopy & demonstration of CMV infection (Culture,
histopathological testing, immunohistochemical analysis, or in situ hybridization) in a GI biopsy].
CMV hepatitis: {Increase
bilirubin and/or enzymes
e LFT., é abstruction of any other
documented cause of hepatitis & detection of CMV infection (by culture,
histopathologic testing, immunohistochemical analysis, or321)`zin situ
hybridization) in liver biopsy}.
Resistance to
ttt.: The viral isolate UL97 mutation,
accounts for > 90 % of
ganciclovir-resistant CMV isolates. Point mutations in UL97
protein kinase gene lead to changes tht prevent
phosphorrylation of ganciclovir. This finding necessities a change to 2nd
-line therapy: foscarnet,
60 mg/kg/8
h.. After 2 w. of full-dose, maintenance-dose (90-120 mg/kg
daily) of IV foscarnet shd be started. Recommendations for managing CMV
resistance are to increase the dose of ganciclovir for mild/moderate dis. or switch to foscarnet
for more sev. dis., with or without continued use of ganciclovir. (Medscape).
Preemptive therapy: is
initiated to prevent the progression of CMV disease when {Viral load reaches a predetermined
threshold level in an a.Sm.tic ptn. who hs bn screened frequently
for viral replication}. Adv. :[Selective
use (vs universal) of antiviral agents & dcrease drug cost, fewer drug-ass.
toxicities, and dcr. risk for late-onset CMV infc.]. Disadv. incl.: {High cost & logistical difficulties ass. é frequent
monitoring of CMV viral load, and the potential for aggressive dis. and
indirect effects of CMV infc e allograft while ptn. is being monitored}. (Medscape).
CMV &
Relapse:If the patient hs a typical pattern of
relapse after stopping preemptive therapy, the best ttt is to reinitiate oral valganciclovir
because no information is given that wd lead one to suspect antiviral
resistance tht wd be an indication for changing the drug. Either IV ganciclovir
(5 mg/kg twice daily) or oral ganciclovir (900 mg twice daily) are appropriate for ttt. of CMV dis., but IV ganciclovir is
generally used in children, when dis. is life-threatening, or when oral
medication is not tolerated or well absorbed. (Medscape).
Treatment of CMV Relapse: Until
recently, IV. ganciclovir
ws the gold-standard ttt of CMV dis.. Oral valganciclovir ws shown in VICTOR trial
to be noninferior to IV ganciclovir for ttt. of CMV in SOT
recipients e nonlife-threaten-ing dis.. It is important to give the appropriate
doses of valganciclovir or ganciclovir to dcr. the risk for develop
of resistance & recurrence of CMV dis.. Twice daily dosing is
recomm. for ttt. of dis. in pt. e normal R. function e optimal duration of ttt.
is determined by monitoring viral load weekly & treating until 1 or 2
consecutive negative samples are obtained, but not for < 2
w.. (Medscape).
CMV Dis. & Rejection:The association between Ac. rejection & CMV dis.
is bid-irectional;
the im/m. drugs used to prevent & treat Rj incr. risk for CMV dis.
and CMV dis. incr. the risk for Ac. rejection. (Medscape).
“Dosage*
Recommendations for Oral Valganciclovir in Adults”.
CrCl. (mL/min) |
|
Induction Dose |
|
Maintenance/Prevention Dose |
≥60 |
|
900 mg
twice daily |
|
900 mg
once daily |
40-59 |
|
450 mg
twice daily |
|
450 mg
once daily |
25-39 |
|
450 mg
once daily |
|
450 mg
every 2 days |
10-24 |
|
450 mg
every 2 days |
|
450 mg
twice weekly |
<10 (on HDX.) |
|
Not recommended |
|
Not recommended. |
*450-mg tablets, (Medscape).
Summary & Conclusions:
The
burden of CMV dis. after SOT is significant. Direct effects incl.
a clinical spectrum of dis. fr. aSm.tic viremia to life-threatening
tissue-invasive dis.. Indirect effects incl. allograft dysfunction & loss,
incr. risk for other opportunistic infections, lymphoproliferative diso. & death.
The best approach for CMV dis. in SOT is prevention, but it still debatable wch strategy: prophylaxis or preemptive therapy,
is optimal. Ganciclovir
& valganciclovir remain the best options for prevention &
ttt. of CMV dis. in SOT, but they‘re costly & ass. é toxicity. A boxed warning about hematologic
toxicity, carcinogenicity, teratogenicity & impairment of fertility is incl.
in prescribing information for both drugs. CMV dis. after SOT
continues to be ass. é adverse outcomes; thus, new preventive strategies
are needed. N.B.:
CMV-seronegative ptn. are at highest risk for CMV post-transplant when the donor organ
is from CMV-sero+ve.
Type of organ Tx. is a risk f. for CMV infection after transplant.
{Lung, heart, small intestine, pancreas & kidney-pancreas
transplant} recipients are at greater risk for CMV infection than kidney & liver
Tx. recipients.
Universal Prox.: giving antiviral ttt to either all
ptns or to a select group to prevent CMV infection and dcr. the
direct & indirect effects of CMV infection.
The first-line empiric ttt. for CMV dis.is: IV ganciclovir 5 mg/kg twice
daily
The gold standard ttt for CMV
dis. is IV ganciclovir,
5 mg/kg twice daily and should be adjusted based on the patient's renal function (Medscape).
Q.687. Comment
briefly on P.j. infection in R.Tx.?
A. C.P. 🠊[fever- SOB - non-productive cough.].
- Plain x-ray: [Bilateral
interstitial alveolar infiltrate].
- Dgx.: Demonstration of organism
é sp. stain é sputum, BAL of limited value (low viral burden).
- ttt.: SMX/TMP 🠊may increase s. Cr. without affecting GFR. 👈
Q.688.What is the spectrum of SMX/TMP prophylaxis?
A. SMX/TMP Prox: = (TONOLIP): ✌ ✌
1) Toxoplasmosis.
2) Nocardiosis.
3) Listeriosis.
4) P.C.
- Alternatively 🠊Dabsone ± pyramethamine.
Q.689. What are the clinical
manifestations of CMV
infection?
Systemic: [fever-malaise-myalgia]🠊 Non-specific, but important CLUE for Dgx. 🔑
B.M.🠊Leukopenia🠊mild. 🠊🠟Aza & MMF dose. “Gancyclovir” 🠊 leukopenia also.
Lungs🠊 Pneumonitis, life threatening. 👽
G.I. 🠊 Inflamm./ulceration🠊 esophagus & colon.🠊 Occur late, life threatening.
Liver 🠊Hepatitis 🠊 Rare.
Kidney 🠊 RAS. ⭕⭕
Eye(Retina)🠊Blurred vision,
flashes, Chorioretinitis 🠊Late & rare. 👁👓
Q.690.What is “polyoma” virus nephropathy? How to
treat?
A. It is the dis. of modern immunosuppression,
occur due to shedding of the uro-thelial cells. Dgx. 🠊Biopsy 🠊[Interstitial
nephritis, tubular cell injury+ Intranuclear tub. cell inclusions +
+ve immunoperoxidase].
Ttt.: [Decrease
the dose of im/m.- Leflunomide + IgG. + Cidofovir (low dose)].
Q.691. Comment on “vaccination” in R.
transplantation?
A. There
are general roles
to be considered:
① Immunization should be completed 4 w. before T.x.
② No vaccination é 1st
6 m. post
T.x.
③ No live
attenuated vaccine after T.x. (C.I.).
-
House-hold
contacts è yearly immunization
to influenza.
wish you all the success Dr/Fedaey
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