Q. 716. What are other types of rejection?
Solid-organ transplant (SOT) TR are immunocompromised and may be at higher
risk for severe COVID-19 disease as compared to general
population. Two large observational studies of SOT recipients with COVID-19, about 80-90 % of ptns required hospitalization;
of those, nearly 40
% required intensive care & 30 % required mechanical
ventilation. At one month, mortality (MR) exceeds > 20 %. These
findings suggest: TR are at a higher risk for poor outcomes,
multivariate analyses in both studies reported that age & chronic co-morbidities
were the primary drivers of MR rather than immunosuppression.
Solid-organ transplant (SOT) TR are immunocompromised and may be at higher risk for severe COVID-19 disease as compared to general population. Two large observational studies of SOT recipients with COVID-19, about 80-90 % of ptns required hospitalization; of those, nearly 40 % required intensive care & 30 % required mechanical ventilation. At one month, mortality (MR) exceeds > 20 %. These findings suggest: TR are at a higher risk for poor outcomes, multivariate analyses in both studies reported that age & chronic co-morbidities were the primary drivers of MR rather than immunosuppression.
KIDNEY TRANSPLANT
Acute Vascular rejection
Q. 716. What are other types of rejection?
A. Other types include: 👌
v Hyperacute Rj. 🠊Occur
due to presence of “preformed recipient A.B.”
reacting é endothelial surface of allograft, mainly
occur é recurrent blood TX
& pregnancy.
v Accelerated Ac. Rj. 🠊2-5 d. (us. Humoral immune).
v Ac. CNI. toxicity (Csp.&Tcrol.)🠊Afferent G. V.C.🠊Ac. Reversible decrease é GFR.
Q. 717. What is the difference between AMR/AHR & ACR? What
is the difference in treatment?
A.AMR/AHR (Ac.
A.B. mediated Rj. /Ac. humoral Rj.)🠊[🠝3 d.- Donor reactive A.B.- Neutrophil polymorph in G. & peri-tub. Cpll.-
C4 st. é peritub. cpll.- No tubulitis.]
* While ACR (Ac. cell.
Rj.)🠊[🠝 5 d.+ tubulitis ☜
لازم ] + Abs.
of :
1) Donor reactive A.B.
2) C4
d. st. é peritub. Cpll.
3) Neutrophil polymorph é G. &
peritubuer. cpll.
A. While ttt.
of ACR 🠊[Steroids] mainly, AMR/AHR ttt. é 🠊[ Pph.+ Steroids+ I.G.] is mandatory.
Q. 718. How can CNI.s be toxic? How to treat?
A. Ac. CNI.s🠊Affer. G.V.C🠊Pre-renal Reversible 🠋GFR & 🠝 s. Cr.. It’s us.
dose-dependent & Responds to dose reduction.
Q. 719. So, How can you differentiate between Ac. CNI.s & Ac. Rj.?
A. …..
Both can
Co-exist ! ولكن ! ,
But: Pointers to ➳ Ac. CNI.s🠊 👌
1) Sn. of extra-renal
toxicity. e.g. severe tremors.
2) Moderate rise in s.Cr.<25 % over baseline.
3) High trough
level of Csp> 350 ng/ml & Tacro>15 ng/ml.
*** While, in Ac. Rj. 🠊 ✌
1. Low drug level, e.g.< 150 ng/ml.
2. Rapid Non-Plateau rise in s. Cr.
Q.720.Then, how to consider a final decision in this problem? 👆
A. Renal Biopsy, esp. in a high risk ptn. i.e.: 👌
1) Previous graft rejection.
2) Highly sensitized ptn.
(blood. T.X. & pregnancy).
3) High risk of early recurrence
of the Iry disease e.g. FSGS.
Q.721. How to D.D. ACR. (Ac. cellular
Rj.) from Ac. allergic interstitial nephritis?
A. Both have.:🠊{1. Eosinophilia.
2. Mononuclear cell infiltration. }, but,
- Ac.
allergic interstitial nephritis 🠊[fever + Rash.]
after ingestion of a new drug.
-While,
ACR.🠊Endothelialitis. … (Polyoma
virus) should be considered in D.D.
Q.722. What is late acute rejection? ⌚ Mention the accused factors?
A. Late Ac.
Rj. = Rj. >6
m., post Tx.
Etiology: Like
early acute Rj.: [Shock, ACEI, UT. Ob. & NSAID.
].
Q.723. What is new in ABO desensitization programs in renal transplantation?
A. Poor
outcomes combined é
improvement in results using DDA limited ABOI T.x. in U.S. in the
past. However, an extreme
lack of available deceased donor encouraged investigation é Dsz for ABOI/LDA
in Japan🠊successful
long-term results combined é subsequent successful short-term results fr. U.S. have
renewed interest in this procedure.
-[Pph, immunoadsorption, IVIG., rabbit ATG,
anti-IL-2 receptor A.B.- splenectomy, anti-CD20 (Rituximab)]or a
combination therapy, all have been tried, but
it’s unclear which strategy is more effective or cost effective.
While a variety of protocols seem to be effective in allowing successful
T.x. across blood group barrier, much work remains to
determine the optimal protocols.
Q.724. As regard HLA sensitization (Ssz) what are the types & importance of anti-HLA antibodies?
A. ESRD ptn.
tht are sensitized to HLA Ag via bld products, pregnancy, or prior T.x. us. hs A.B. directed agnst
deceased donor & potential living donor kid. Assays that define Ssz detect 🠊A.B. agnst broad spectrum of potential
donors, while crossmatch (Crossm) identifies 🠊A.B. agnst a specific
donor. Depending upon assay, different types of A.B. & their clinical
relevance can be identified. Ig.G vs.M: Ig.G
A.B.
detected by Ssz or crossm are considered to reflect true Ssz
agnst HLA Ag., while IgM are Not
considered typical response.
T vs.
B cell: A.B. detected agnst T cells have been considered to
represent true
anti-HLA Ssz agst class I. Ag. By
comparison, T cell -ve, B cell +ve crossm results have been
considered to represent HLA class II
A.B. of less significance. C. fixing vs non fixing: A.B. tht must fix C. to produce a +ve
assay are considered cytotoxic & of clinical
importance. A.B. detected by means independent of C. fixation, e.g. flow cytometry, may detect other A.B.
that may not be cytotoxic & of
unclear clinical significance. While data suggest: +ve flow crossm is associated é 🠝risk of Rj. & 🠟graft
survival,
+ve
predictive value of this assay is likely dependent upon whether or not
donor A.B. are present and, if so, whether A.B. is able
to fix C. Most assays detect pres. of A.B.
but not the precise HLA specificity. Assays to
identify sp. HLA Ag. targeted require more time to perform & can only
be undertaken in settings such as LDA,
when time constraints are not an issue. T.x. shd Not 👆proceed
é evid. of +ve crossm 2ndry
to cytotoxic IgG anti-HLA AB.
Q.725. What are the desensitization protocols (Dsz) available?
A. Two protocols are used to
desensitize potential recip. é preformed HLA A.B.:
Dsz cn be used for a potential recipient of a LDA é defined HLA/DSA against donor to🠋specific A.B.. It can also be used for an individual on the DDA waiting list broadly sensitized to HLA Ag. (PRA ≥ 30%) é repeated +ve crossm. One method uses high dose IVIG & the other uses low dose IVIG & Pph in a protocol identical to that described for ABOI Tx.. Monitoring for AMR post-Tx. consists of: 👌
(1) Lab. Evaluation.
(2) Monitoring DSA titers.
(3) Protocol biopsies.
I. “High dose”
IVIG (HiiV): Adv. incl.:{ability to desensitize ptn on DDA waiting list
& potential LDA recip.. It’s much less resource intense
& less expensive thn low dose IVIG. Ptn on HDX.
cn receive monthly IVIG
while undergoing Dx. ttt.}.
Disadv. incl.:[lack
of experience in either ABOI or é high titer HLA DSA. Crossm
monitoring & monitoring of post-Tx. DSAs for 3 w. is limited to the
less sensitive NIH-CDC assay 2ndry to interfere of
high d. IVIG é other more sensitive
assays]. Using less sensitive NIH-CDC for crossm
screening rather more sensitive 👉AHG- assay, one could infer tht
recipient in HiiV will be more sensitized (false –ve crossm)
& thus at higher risk of Rj. comp. to low dose IVIG, using AHG
assay. “HiiV” S.E.:🠊[hd, fever, msc.
pain, S.O.B. & chest
discomfort ]. ttt.: by using products é
osmolality mimicking tht of plasma.
Giving iso-osmolar IVIG
dur. DX allows for simultaneous correction of vol. issues. Keeping
individual guidelines for rate of infusion shd be foll. to 🠋
complications of high osmotic load,
wch. cn be avoided by using 👉[Non-sucrose
based, isoosmolar
product].
II. Low dose IVIG (Lodiv): Adv.:[documented
use é high titer anti-HLA A.B. é Dsz & successful Tx. é DSA titers of up to
1:256]. Although high titer DSA can respond to Lodiv, numerous
preTx. sessions us. required to get🠊adequate
low titer+ numerous post-Tx. sessions
to limit rise of DSA titers & 🠋
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