ABOI Kidney Transplant-Immunosuppressive Protocol for Optimal Outcome
Dr. Deepak Shankar Ray
Good morning, I am Dr. Deepak Ray. I am head of the nephrology and the Reynolds transplantation in the R&D hospital, Polka Tath. I am also the clinical governance lead of the Reynolds transplantation of the whole of Narayana hospital group of India. Besides that, I am involved with TTS transplant activities. I was vice president of Indian Society of the program transplantation. We in R&D do a large number of transplant, around 500 plus in a year. It is a large transplant center and we do lot of abu incompatible transplant. We have formulated our protocol which is suitable for India because it is low cost and very effective protocol which we have been advocating large 10 to more than 10 years and we do regular workshops and train people on ABY transplants and number of people from different corners of India have had land in our workshop. They come here for a couple of days, learn it and go back and start transplant. So, we are happy that we have been able to be a part of increasing the transplant numbers all over India by increasing the living donor pool from the family. With this today, I am going to speak about ABYI kidney transplant. The way we do it in our hospital, I will just be limited to be very practical aspects and very simple way how you can do. Still, I know there is a fear for doing abu incompatible. A lot of people are scared about this but there is nothing to scare, nothing to be scared about this and I will start straight away with my PPTs. Thank you. See, as you know, incidence of ESRD in India is probably around 230 per million population per year. This is 2013 data from kidney international. We do not have a study after that but I think it is higher than this and around 2.2 lakhs to 2.75 lakhs, new patients need RRT every year. Annual growth of ESRD is 10 to 20 percent. Rinal transplantation rate, even though we are the third largest country in the world doing the Rinal transplantation after US and China but our rate is if we consider our population or rate is 4, it is 3.25 per million per year and as we know only probably 10 percent of our requiring present under the Rinal transplantation because major reason is non-availability of donor and then besides the finance part of it, besides the availability of good transplant centers, surgeons, nephrologists, these all points contribute to this low number of transplant we do in India. This is the notodata and last year we did total around 9,000 or 10,000 living donor transplant around 1 and 1 half thousand disease donor transplant. This year this has gone up to 17,000 but still the number is low. So how do we expand the donor? One is doing a new in compatible transplant. Long back there was a study from CMC Baylor where they showed that 40 percent of life donors in the family are lost if you do not do incompatible blood group transplants. So one can go for a new in compatible transplant, one can go for paired donor exchange transplant. In our entire we started paired donor in 2005 probably the first in India. Presently our stress is more on Abi. We have done quite a good number of paired donor transplant but we have shifted mostly to Abi because less complication legal and medical. Then one can do this expression in HLS and state recipients and of course we have to increase where far away from the number we should have in these donor transplant. How do you formulate immunosuppressive protocol for your patient for whether Abi or HLS, Ms. Merth or even normal transplant? It should be a simple protocol can be followed by everybody. There should be low rejection rate, low infection rate. There should be good graft and patient survival and it should be definitely affordable. So we within the reach of majority. We started Abi in compatible transplant in 2013 and then gradually we picked up we do around 32, 33 transplant in a year except for the COVID year when there was a dip but and we have done till end of last year, 283 Abi in compatible transplants. When you do Abi in compatible transplant you have to follow certain decent-sc customization protocols. One is removal of circulating Abi antibodies. You have to use the extract for burial method. It could be plasma phoresis, it could be double filtration plasma phoresis or immunohegyptium. The number of treatment sessions will depend on your antibody how fast they are falling to an expected level. How many plasma phoresis or DFPP or even immunohegyptium unit and the choice of techniques will be related to the availability, the cost of technique and comfort with the technique. If your technicians, if your dialysis unit is well equipped with a machine and can do good plasma exchange, it is cheaper and good modality of addition. Besides that we use retoxima for cell depletion. It is anti-CD20 monoclonal antibody, bioincent CD20 on immature and mature B cell and it results in depletion of B cell. Anti-effect remains at least more than one year. We have studied that so retoxima is a kind of people have started doing without retoxima but to my mind you should be using retoxima. Then immunoglob, immunomodulation of the recipient's immune system, we do use IVIG for that. It replaces the immunoglobulin removed in the plasma process. You remove a lot of proteins or immunoglobulins are removed. So IVIG replaces that. It down-vegulates the complements. It interacts with the F-C receptors. It inhibits CD19 expression on activated B cells, complement and allodactive T cells. In-evision of B and T cell proliferation, in-evision of CD8 T cell cytotoxicity and it increases the hypothesis of B cells. Then for maintenance we use the normal whatever we use in abial compatible. We use that in abial incompatibility, the antimetrobloids and loaders teres and CNI's. We are requested to see this slide well. This is our protocol and this is also published in multiple journals multiple times. You can take a picture of this. We start giving retoxymap two weeks prior to the expected data transplant. We give 100 or 200 milligram. If the antibody titer is 512 or less, we give 100 milligram. If it is more than 512, we give 200 milligram. Simultaneously, we start with steroid 20 milligram per day. Tectrolimus 0.1 milligram per kg, keeping a level of 8 to 12 nanogram per ml. And microphenylate, we give 1.5 gram a day. We admit the percentage around seven days prior to the transplant. We do plasma exchange, alternating with the IVIG. Suppose day one, we do plasma exchange, negative we do IVIG. And next day we do plasma exchange. For plasma exchange, we remove 30 ml per kg of plasma and we replenish it with the fresh frozen plasma of that bonus blood group. We use 5 gram of IVIG on alternate day. It's a low dose. And we then when consecutively antibody titer comes down, present day our target is 1.64. If it is less than 1.64 or as at 1.64 for conjugative free death, we send him to surgery. And we use induction as in our abio-compatible. We use induction also in abio-in-competive transplant. 3 milligram per kg of ATG, 1.51 day 0 and 1.51 day 1. Over the period, we have modified our preconditioning as we gained experience. Initially, our target antibody titer was 1.2-8 and then it was raised to 1.2-32 and finally 1.64. The initial prednisolone was started at 50 mg per day with a maintenance of 7.5 mg per day but it is now reduced to 20 mg per day initially. And then we climbed down to 5 mg per day in a longer run. Present with the best line antibody titer of 1.62, we may or may not do any plasma exchange. If we do, we will do a single plasma exchange. If the patient has antibody titer of 1.16 or less, we do not do any plasma exchange. We give a dose of retoxin map, that immunosuppressant and two weeks later, we take off the transplant. Antibody titers are monitored, forced transplant when the patient is in-house or in the hospital till discharged. That's because it is free for them. Forced discharge, we do not monitor antibody titers. We only do antibody titers if there is a clinical indication to create a dose of or something happened, then only we do the estimated antibody titers. We do not give any prophylactic plasm, per diaphragm, for this process, forced transplantation. That's not required. We initially were giving around 500 mg retoxin map, then we dropped down to 200 mg, then following our study of ours, we give 100 mg if the antibody titer is 512 or less and we give 200 mg, if it is more than 512. As I said, we do conventional plasma process which is available in every dialysis unit. So it is EEG. You do not have to do or procure any extra machineries of this. The volume exchange is 30 ml per kg and we replacement fluid is the FFP of the donor's blood group. This is our first publication in transplant proceedings in 1916 when we said in Eastern India, in a developing country, you can do a immune-competable transplant comfortably with a good result. We compared between Abuo incompatible and Abuo compatible patients. We took 30 transplant Abuo incompatible, 30 Abuo compatible and prospectively studied them for a year. There was in the Abuo incompatible group, there was one antibody-mediated rejection which was cell-related antibody, not Abuo-related antibody, which should be successfully treated. Abuo compatible group, there was a T cell-mediated rejection which was also successfully treated. There was one death on each group because of SNR2 vector in Abuo compatible group and because of a aspergillosis services in Abuo incompatible group. The creatinine in both the groups have remained same till one year. The GFR has been similar. The rejection rate were similar. There was three at TCMR in Abuo incompatible group and one MR, but statistically both are similar and post-transplant hospitals stay were similar in both of them. The infection rates were also similar. The result of Abuo incompatible is equivalent to Abuo compatible at least in short tons with this study of ours. This study was published in South D. Journal of Pediatric and Transplantation. Then there is a fear always. We have come across number of people. If the initial antibody titers is high, they don't do the transplant, fearing that it is not possible and there are very gents and it is not a group. To prove that, we did a study where we took patients with 1 is to 256 or less antibody titers, initial antibody titers and another group with more than 1 is to 256 antibody titers. We studied them for a month and we found that baseline antibody titers is a no-contrain detection for Abuo transplantation. No significant difference of the outcome between high and low antibody titers groups. Comparable graft function, the rejection episodes, infection and graft patients are viable in both groups, whether the titers are high or low. So, high Abu antibody titers should not be a deterrent for Abuo transplantation. This is a publicist guest report from our hospital where we have done antibody removal and successful transplant in a patient with more than 8,000 antibody titers to start with. Our laboratory can go up to 8,000 so it could have been 16 or 32 or even 64,000. We do not know but it was very high. So, this says that you can any amount of antibody titers should not be a deterrent for your taking of the patient for transplant and it doesn't mean always a high titer will take more time to come down to the target level. It can, it may take less time, suddenly it may come down. This all kind of this phenomenon we have seen in our practice. We also studied a longer term 75 Abu incompatible kidney transplant compared with the same time 75 Abuo compatible kidney transplant and the main period of observation was 58, that means 5 years. All relations of donors were wife, father, mother, sister, second degree relations, brothers, etc. And the antibody titers had been high in 2% it was 1, 1 to 4,000, 1 to 2,300, 1 to 1,007 and we successfully reduce it. If you see there are 5% where we started, we did transplant with 1 to 64 antibody titers. So, 64 is present or target cut up. The duration of admission was 20.7 days that is because pre transplant we admit them for the plasmophoresis and IVIG and they discharged creatinine was 1.5 milligram. The second table shows the comparative between a Abuo compatible and incompatible. Creatinine for over 2 years it was similar. The mortality was also similar. In Abuo incompatible this herbivol was 90.7 at 5 years and in the Abuo compatible one it is 93.3 years. It is slightly high in the Abuo compatible but statistically there is no difference. Similarly, if you see the rejection rates were similar in both the patient. It was slightly high again in Abuo incompatible patients. The T cell remediated rejection were slightly high but again statistically both were similar. The infection rate requiring infections requiring admission were also similar in both the groups. This paper of our what mentor mentee award in large TTS conference at Buenos Aires. We also do command HLA and Abuo decentralization. This is a patient of ours who came to us for third transplant. First one happened in 90s, second in 2010-11 and then for the third one she came to us with Mother Edonor. Mother's blood group was B and Herro. They had also HLA and C had also HLA antibody. We successfully decided and transplanted it is now 5 years, 4 years, 4 and half years. She has got married, she is working as a teacher in school and presently she is also pregnant. This is a very successful story where hard transplant HLA antibodies, Abuo antibodies and successful transplant and patients going to pregnancy. So how do we reduce the infection complications? We reduce the dose of retertumum and we have a publication where we compared 52% to 26% with 100 mg of retertumum and 26% with 200 mg. And we observed them for a year and we found the results have been similar whether you give 100 or 200 but if you give 200 the infection rate was significantly higher. So if the antibody titer is 512 or less reduce the retertum up to 100 mg. We also use a lower dose of anti proliferative agent, microphenolate, no mofatil, 1.5 grams and then we reduce to one gram post transplant after six months. We limit the number of plasma exchange by keeping the target antibody titer of 1 is to 64. Japanese centers have witnessed that less infection happens if your plasma phytuses are less in number. And we give long-term prophylaxis with co-tra, maxial and bulgum cyclobear. We have much lesser incidence of CMB and BKV infections. This paper of hour between 100 and comparison of 100 and 200 mg retertum map have been published in transplant proceedings. This is a combined data from 25 centers from all over India. It was recently published in the transplantation journal. We have together 1759 trans, Abiy transplants which were compared with 33,000 compatible transplant. It's a retrospective study and the study found that mortality is 9.4% blood loss was 7.7%. Bapsip proven acute rejection was around 13% and infection was 17% more or less. Results of Abiyu in competitive transplants were and we are a large contributor to this paper which was published. For us in India, we should do things specially in medicine which is inclusive of all classes. We have poor economic and lower middle class people which we should take with us. And India is known to reduce the cost. In 23rd order, we sent Chandran to South Pole of Moon and the mission cost was 75 million USD or 615 crore whereas the USA-NASA Moon mission is 93 billion USD per atom is Moon mission. And they even Hollywood picture was more than 600 15 pours which we spent for only. There are very few papers on the cost. This is a paper from USA where the Abiyu cost have been doubled at the time of transplant. It was though had decreased but it was also high and far second and third year. That's because probably in the USA they used last amount of immunosuppressive sub-decent and the cost remains high. They will have more infections. This is from Professor Tanabe Jaapan. I reviewed this article where the cost at the time of surgery was high in Abiyu and compatible one but it was normal equal in the first year and second year and cumulative cost were similar. The P-lelu being 0.08 are not significant. We have been able to reduce the cost by low-dose using low-dose retoximap using plasma exchange and in place of DFPP or immuno-adjunction which are expensive using FFP instead of albumin using low-dose IVIG. We have kept an antibody titer of 1 is to 64 so our plasma exchanges numbers are less. Number of plasma exchange we require are less. Post transplant monitoring is not done so first is served and we don't give we only give plasma exchange for transplant if it is required. We don't give prophylaxis plasma exchange and if the patient cannot afford we change over to azacra suffering in place of microphenolate at six months. If we talk about plasma filter first around 8,000 FFPs are 500 per unit and you will need around 6 to 8 FFPs each plasma exchange IVIG per 12500 retoximap per 4500. Plasma filtration procedure cost around 1500 in our hospital expenses of FBOI get T for 5 plasma percis will be around 1 lakh and if we have to do around 7.8 then it will be maximum 2 lakhs. So to conclude FBO in compatible renal transplantation with plasma percis single-dose retoximap, low-dose IVIG in combination of standard tripliminous suppression can be performed with excellent results. Resorts are comparable with FBO compatible transplants only moderate escalation of cost no additional infrastructure required and by doing FBO in compatible transplant we can increase the donor pool by 32-35 percent. Thank you for your patience hearing.
