INFECTED ALLOGRAFT

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 2/3^rds 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 2^nd -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.

ƒ Lungs🠊 Pneumonitis, life threatening.  👽

„ G.I. 🠊 Inflamm./ulceration🠊 esophagus & colon.🠊 Occur late, life threatening.

… Liver 🠊Hepatitis  🠊 Rare.

† Kidney 🠊œ 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.