Q.679. Give the D.D. of Post- T.x. infection?

KIDNEY TRANSPLANT

Allograft in renal transplantation

II. Infection

 

Q.679. Give the D.D. of Post- T.x. infection?

A. Post-T.x. infection:

I. 0-1 m.: Conven. nosocomial infection:[HSV- Candida Albicans - onset of (HBV/HCV)].

II. 1-6 m.: (Opportunestic” non-conventional” infections):

·         Viral:[C.M.V.- E.B.V.- H.Z.V.(varicella zoster v.)]: Antiviral: 3-6 m. & SMX/TMP 🠊 6-12 m.

·         Bacterial: [T.B.- Pneumonia- wound & catheter infection].

·         Fungal: [P.J. (Pneumocystis Jerovecii.)- Cryptococcosis- Aspergillosis].

·         Parasitic: [Toxoplasmosis-Leishmania- Strongloidosis].

III. >6 m.: [CMV. Chorioretinitis & Colitis – P.K. papilloma v.] 🠊 Risk 🠟gradually, ptn. either: (i) Good allog. function🠊 No need for more im/m. & rare opp-ortunistic infc..  (ii) Poor allog. function 🠊 Risky due to accumulative im/m. 🠊 So, Long-term Prox. é SMX/TMP. is warranted.

Q.680. What harm can CMV cause to the renal allograft? And what harm can B.K.V cause to the renal allograft?

A. CMV & renal allograft:

1)   A.T.N.

2)   Allog. dysfunction.

3)   Decreased R. perfusion.

4)   R.A.S.    👍

Other organs : [hepatitis-pneumonitis- chorioretinitis (after 6 m)- meningeo-encephalitis- oesphageal ulceration- colitis- G.I. bleeding].  (see also Q. Q.686).

B.K.V & the renal allograft:

- ✌ :{Tubulointerstitial nephritis + ureteral stenosis. }.

Q.681. What are the general💢 policies of organ donors with HCV?

A.Due to high prevalence of HCV among recipient of organs fr. anti-HCV +ve donors, several organ procurement organizations hs a policy of testing all cadaver organ donors for anti-HCV & restricting use of organs fr. anti-HCV +ve donors to life-saving Tx. (heart, liver, or lung). Similar policies were recommended by U.S. Public Health Service Inter-Agency Guidelines. A complete moratorium on Tx. of organs fr. anti-HCV +ve donors into kidney recipient may not be appropriate for the following:

1)   Wide prevalence of liver dis. & HCV infc. after org. Tx. fr. anti-HCV+ve donors

2)   Abs. of definitive evidence of a detrimental effect on ptn. survival.

3)   The current shortage of cadaver kidney.

4)   The constantly growing waiting list for organ Tx.

Short-term data on outcomes é anti-HCV+ve recipient of kidney from anti-HCV +ve donors as well as evid. tht mixed infection. (HCV infection é more thn one HCV-genotype) don’t adversely affect survival among ESRD ptn justify further study of strategy of allocating kid. fr. anti-HCV +ve organ donors to anti-HCV +ve Tx candidates. A better alternative seems to be a policy of Tx. Kidney from anti-HCV+ve donors to only HCV RNA+ve recipient, which’s consistent é 2008 KDIGO guidelines. Preliminary data from Tx. centers in Spain demonstrated no differences in liver dis. & ptn. survival between HCV RNA +ve recipient of kidney from anti-HCV +ve donors & anti-HCV +ve recip. of kidney from anti-HCV-ve donors. Data from a survey include: 147 of 245 R.Tx. centers in U.S. indicated tht: 49 % of these centers use HCV sero+ve donors .

Q.682.What is the effect of pre-transplantation anti-HCV status on post-transplantation clinical outcome?

A. Anti-HCV +ve ptns before Tx. have a significant increase risk of post-Tx. liver dis.. CAH & its sequelae are the principal forms of liver involvement. Also, unusual form of liver dis. é severe cholestasis & rapidly progressive liver failure has been described in a few ptns. é HCV infection who undergo R.Tx.. This condition, termed fibrosing cholestatic hepatitis, is ch.ch. by prominent cholestasis & extensive fibrosis.

Overall, post-Tx. liver disease is an important clinical problem since 11-49 % of R.Tx. recip. are anti-HCV+ve. Studies from New England Organ Bank have shown that relative risk of post-Tx. liver disease was 5.0 for recip. é anti-HCV prior to Tx.. In add., a survey of rel. studies has revealed: post-Tx. liver dis. occ. in 19-64% of recipient é anti-HCV comp. to only 1-30% among recipient without anti-HCV .

R.Tx. in ptn. previously infected é HCV is associated é incr. viral proliferation🠞1.8-30.3-fold increase in viral titer. An🠉viral titer, however, may not be associated é increase risk of post-Tx. liver dis.. Among HCV RNA ptn, titer of HCV RNA was no different among ptn.s with & without postTx. liver dis.. Furthermore, post-Tx. viral load was similar in ptn.s é mild hist. changes on liver biopsy or ch. changes, and there ws no ass. between transaminase patterns & viral load level. These data suggest: f. other thn viral load determine risk of liver dis. among Tx. recipient é HCV infec..

Liver inj. progression of may be slower in ptn who undergo R.Tx. as compared to those on waiting list. This was shown in retrospective analysis of liver biopsies obtained before & after R.Tx. among 31 HCV+ve ptn & comp. to biopsies of 13 HCV-ptn who remained on waiting list . In general, ptns on waiting list were more likely to have progression of liver fibrosis (62 vs 23 % among those who were Tx.). Although studies consistently show 🠉risk of post-tx. liver dis. é anti-HCV +ve, conflicting results surround the question: whether this’s associated é 🠟survival. 3 studies failed to detect significant differences in survival between recip. with & without anti-HCV prior to Tx..

In contrast, several studies hv shown “lower survival” é pre-Tx. evid. of HCV infection : Data fr. New England Organ Bank: recipient é preTx. anti-HCV hd a 3.3-fold higher risk of death & a 9.9-fold higher risk of death due to sepsis . A retrospective study from France evaluated 500 HBV-ve ptn é R.F. who underwent Tx.; survival & causes of death post-Tx. were comp. among anti-HCV +ve & -ve ptn. : HCV infection was associated. é a significant 🠉in M.R..The🠉M.R. was principally due to liver dis. & sepsis. To assess effects of HCV on outcomes post-Tx., a 2005 meta-analysis ws performed: Hepatic cancer & cirrhosis were significant more frequent causes of death é anti-HCV A.B.

 

Q.683. What is the impact of HCV genotype on survival after R.Tx.?

A. There’re limited data concerning the impact of different HCV genotypes on survival after Tx. Data fr. New England Organ Bank revealed: patient survival did not vary significantly with genotype .    

Q.684. What is the effect of HCV infection upon survival with dialysis or renal transplantation?

A. Despite pres. of anti-HCV A.B. at time of R.Tx. may be ass. éincr. risk of death, it’s not yet known whether survival incr. é RRT é DX. oré Tx. Some studies suggest: R.Tx. 🠊better survival thn DX among anti-HCV +ve ptn.: A New England Organ Bank study evaluated risk of death with or without anti-HCV A.B. in R.Tx. waiting list & either did or didn’t receive R. allog. . Tx. was associated é. enhanced survival comp. to continued DX..Relative risk of death was similar between those with & without anti-HCV A.B.. Thus, Tx. resulted in a long-term survival benefit é anti-HCV +ve. Similar findings were noted in another rep. comp. survival among anti-HCV +ve ptn. who underwent R.Tx. é anti-HCV +ve individuals who were acceptable for Tx. but hd not yet undergone the procedure. Outcomes were assessed in ptns é at least 2 y. of follow-up. Despite similar co-morbid C.P., ptns in whom R.Tx. hd bn performed hd a lower M.R. thn those remaining on DX.

So, the possible detrimental effect of Tx. on the course of HCV infc. does not outweigh its long-term beneficial effect on survival in ESRD. Thus, anti-HCV +ve status alone should not👆be considered C.I. for R.Tx. Liver damage (determined by hist. severity) is a strong predictor of liver failure & death after Tx..As a result, in anti-HCV +ve ptn. without evidence of liver disease & in abs. of definite studies demonstrating worse outcomes after R.TX., we suggest: such ptn. should be allowed to make an informed choice of staying on DX or undergoing Tx.. However, Tx. recip. can have hist. evidenceof liver dis. in abs. of🠉s. ALT. So, there should be policy to perform liver biopsies on all anti-HCV +ve ptns awaiting R.Tx. for histopth. evaluation. In ptn. é histological evid. of liver dis., decision to proceed é R.Tx. shouldd be made cautiously, since im/m.🠞🠉viral replication & exacerbate liver dis..