Kidney Transplantation in Sensitized Individual

7/28/2019 Kidney Transplantation in Sensitized Individual

1/32

ATUL DESAI

19/3/12


2/32

Transplantation in HLA sensitized individuals or in ABO

incompatible individuals was contraindicated earlier.

Because of hyperacute rejection or early antibody mediated

rejection.

However, with currently available immunosuppressive

medications & advancement in understanding of AMR,

transplantation in such individuals is possible.


3/32

Sensitized

individual or ABOI

Cadavertransplant wait

list

Living donortransplantation

Paireddonation

Desnesitize

& +veCM TX


4/32

CC

Abdetection

cytotoxicty

Flowcytometry

Solidphaseassay


5/32

Complement dependent lymphocytotoxicity-CDC. : recipient

serum incubated with B cells and T cells from pool of donors.

Complement is added and cell lysis is noted.

Anti human globulin enhanced cytotoxicity: anti humanglobulin is added.

Sensitive, detects low titer and non cytotoxic antibodies


6/32

Even more sensitive antibody assay.

A mixture of target cells composed of lymphocytes from 5-10

donors is used.

Pts serum is mixed with target cells.

Washed and incubated with monoclonal mouse anti CD3 &

CD19/CD20 antibodies.

These antibodies will be conjugated with fluoroscent dyes.

T cells stain red-orange & B cells stain red color, detected by

flow cytometer.


7/32


8/32


9/32

HLA sensitization is not a contraindication for transpalntation.

It represents pts at IMMUNOLOGICAL RISK.

Immunological risk for hyperacute rejection if DSA are very

high, or acute AMR if DSA are low.

NO increased risk in pts with very low level.


10/32

Therefore it is important to asses the level of DSA.

All the tests to detect alloantibodies are qualitative.

However,the level of DSA can be semiquantitatively assessed

using various crossmatch assays.

Serial dilutions in cytotoxicity assay.

Channel shift in FXM


11/32

Cadaver donor list: if the pt has no living donor.

US data: In the United States, approximately 15,000 patients

on the Organ Procurement and Transplantation Network

(OPTN)/

United Network for Organ Sharing (UNOS) cadaver donor

kidney waiting list are sensitized.


12/32

15000

8000 havehigh PRA

>80%


13/32

Desensitization prior to cadaver Tx: IVIG or rituximab used.

Plasmapheresis: requires coordination with Tx surgery date.

Hence can not be used in cadaver tx.


14/32

In a multicenter, double-blinded study, 101 sensitized renalallograft candidates received high-dose IVIG (2 g/kg monthly 4) or equivalent volume placebo.

Baseline PRA levels as determined by a T cell cytotoxicity assaywere similar in both groups (80% in both).

IVIG treatment decreased the PRA by approximately 10% by 4months, but the PRA returned to baseline at 6 months (2 monthsafter the last IVIG infusion) and was equal to that of placebo-treated patients at that time point.

Among dose-adherent patients, 35% (n = 16) IVIG and 17% (n = 8) placebo patients were able to be transplanted. Nine of 17 patients transplanted after IVIG infusion had a

rejection episode, however, compared with only 1 of10 placebo-treated patients.


15/32

D

R

D

R


16/32

An increasingly viable option for sensitized candidates with anotherwise suitable living donor is to perform the transplant

despite the presence of a positive crossmatch.

Treatment protocol depends on the level of DSA in recipient.

High titers of DSA require desensitization prior to Tx.

Low levels need no desensitization, needs careful post Tx

monitoring.


17/32

Need to be desensitized.

The DSA levels need to be reduced prior to Tx

Goal should be to achieve a negative cytotoxicity crossmatch

at the time of transplantation.

2 major approaches : high dose IVIG and plasmapheresis.


18/32

IVIG 2g/kg body wt (max of 140 g)

successful in ameliorating a positive complement-dependent

cytotoxicity crossmatch and permitting successful

transplantation

Patients who fail to respond to one dose of IVIG may respond

subsequently to repeated doses.


19/32

The likelihood of an individual responding to high-dose IVIGtherapy may be predicted by performing an in vitro

crossmatch after adding IVIG to the sera to be studied. A

decrease or blockade of the crossmatch suggests that the

patient would respond in vivo after administration of IVIG.


20/32

the goal of plasmapheresis is to remove DSA physically beforetransplantation and obtain a negative crossmatch at the time of

transplantation.

IVIG usually is given in conjunction with plasmapheresis at a

lower dose of IVIG (typically 5 to 10 g based on body weight)than that used when IVIG is given alone for desensitization.


21/32

IVIG in this approach is given to preventhypogammaglobulinemia associated with multiple

plasmaphereses, although it is possible that it provides some of

the immunomodulatory effect


22/32

Stegall MD, Gloor JM, Waters J, et al: A comparsion of plasmapheresis vs highdose IVIG desensitization in renal allograft recipients

with high levels of donor specific alloantibody. Am J Transplant 6:348, 2006


23/32

Induction : IL2 receptor antagonist or rabbit ATG

Maintainanace: TAC, MMF, steroid


24/32

Hyperacute rejection is very low.

No need of desensitization in them.

However they are at increased risk of early AMR.


25/32


26/32

Reason for AMR in pts with low DSA: result of anamnesticmemory response produced by reexposure of recipient

memory B cells to circulating donor antigen.

Need to prevent memory bcell response.

Induction: ATG, IVIG +/- rituximab.


27/32


28/32


29/32

Monitor DSA.

Aim to keep T cell & B cell channel shift < 300 in the first 2

weeks post Tx.

May need additional IVIG or plasmapheresis in post Tx

period.


30/32

Acute humoral rejection is rare beyond 2 months aftertransplantation in ABO-incompatible and positive-crossmatch

kidney transplant recipients.

Generally, antidonor antibody is lower at this point after

transplantation and is well tolerated by the allograft. Graft survival rates of positive-crossmatch kidney transplants

have been good. Reported 1-year graft survival rates have

been approximately 80%


31/32


32/32

Sensitized

individual or ABOI

Cadavertransplant wait

list

Living donortransplantation

Paireddonation

Desnesitize

& A2 toB/O tx

Documents

Kidney Transplantation in Sensitized Individual