Establishment of deceased donor program in your institute - Why and How?
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The global incidence of end-stage renal disease patients is increasing at a rate of 7% each year. There is a mismatch between the number of people awaiting transplants and those who ultimately receive one. This disparity has prompted a renewed emphasis on the use of expanded criteria donor kidneys. On a worldwide basis, there is an increasing gap between demand and supply. In India, an annual occurrence of approximately 1.5 lakh cases of end-stage renal disease (ESRD) is observed, but only around 11,000 kidney transplants are performed. This stark contrast is primarily attributed to the insufficient availability of kidneys for transplantation. Consequently, a significant disparity persists between the demand for kidney transplants and the limited supply of organs, underscoring the pressing need for strategies to address this challenging gap in healthcare provision.
Utilization of deceased donor kidney can serve to be a vital tool in increasing the number of available kidneys for transplantation, thereby improving the chances of successful transplantation for those in need.
In this episode of TRANSFORuM, Dr. Manish Malik discusses the topic of "Establishment of Deceased Donor Program in Your Institute - Why and How?" The speaker discusses the benefits of setting up a deceased donor program, as well as an overview of the rationale for the deceased donor program and the steps involved of implementing a deceased donor program.
Dr Manish Malik Video
Good evening. Today evening we have a very interesting session from Sanofi and it covers a topic which is very close to my heart which is established by the C's donor program in your institute. Why and how? These are the disclaimers which come as a part of a representation and these are the learning objectives. One, to understand the rationale for the C's donor program, to understand the benefits of implementing the C's donor program and to understand the process of establishing a C's donor program. We will try to take you through all of these objectives in the next half an hour or so. The first part is the rationale for the C's donor program and we all know that there is a major need for the C's donor program in kidney transplantation. The reason being that kidney transplantation is a treatment of choice for ESRD. The number of ESRD patients increasing globally at an eight of seven percent per year and there's a huge gap between the number of patients waiting for transplant and those receiving a transplant and the increasing gap between demand and supply-restricted worldwide and more so in our country. This group, this gap has reduced the interest in the use of ECD kidneys or what we call the expanded criteria donor kidneys and these are used to expand the number of disease donor kidney transplants particularly for elderly recipients and we will add on to it in the next few slides. So what are the statistics for the disease donor program all over the world? If you come to the 2020 data which was published in kidney international and it showed the numbers of kidney transplants per WHO region. We find that in the Americas, if you look at these bars, the green part of the bar is a disease donor and the brownish or the reddish part of the bar is the live donor and in America in that year there were 33,000 over transplants and 68 percent were disease donor. Only in the Europe, similar number, 70 percent were disease donor and in the Pacific region in Australia, Australia again, 63 percent were disease donor but in the south east Asia region, the region where we live, one, the number of transplant itself is very less, only 3.7 per million population which is next only to Africa but the disease donor is only 5.8 percent which in Africa is 25.8 percent and disease donors are transplants performed all over the world and the higher income country is, the larger is the number of these transplants and as I mentioned, the rates are excepted low in southeast Asia much lower than even in the African continent. What are the trends in disease donor transplantation in the US? This was again data published recently. The annual data report 2020 showed that there was a profound implication of COVID-19 pandemic on living donor transplantation and the largest group on the waiting list is 50 to 64 and the proportion of patients about 65 is rising and there's an increase in the count of disease donors and also the new trend is more and more etthigy processed disease donors and what are the challenges in kidney transplantation? These are mentioned as US perspective but of course they are the same Indian perspective that is one, maximizing access to transplant, reducing the excess disparities and of course sustaining long term alograft survival. What are the statistics from our own country? This is very old data, almost 10 year old data and you find that in 2016 or so the state which was number one was Tamil Nadu with 136 donors that is organ donation rate of 1.9 million population followed by Kerala, Maharashtra and Arra 50 odd per total number of donors and Delhi was the way behind only with 20 donors. The annual rate of renal transplant in India is quite low as I mentioned, 3.25 per million population but the disease donor transplants are as low as 0.08 million per per million population per year and there's a logistical challenge due to lack of doctors and hospitals with necessary essential renal care but as we see from this data the disease donors increased particularly in the southern states which is Tamil Nadu, Kerala and Andhra and Karnataka because of the proactive policies of the state government and the PPP which is the public private partnership. What is the current status of disease donor kidney transplant? This is the 2016 data published by Dr. Shahraff and it shows that the prevalence of ESRD requiring transplant is estimated to be around 151 per million population and if an average of these figures is taken 220,000 people require kidney transplantation in India but only around 7.5,000 are done per year in the 250 centers which we have and of these only 10% come from disease donors and the rest 90% come from living donors. And as per the Indian law and its amendments 20 in 2011 there's a provision for required request available to the intensive care doctor to ask for organization in the event of brain death a national registry has been made to look at the outcomes and of course trained transplant coordinators are required for the purpose of counseling relative for organ donation which has increased the disease donor organ rate in India which is shown beautiful in a slide will come sometime later and currently many donors are being lost due to lack of early identification and poor maintenance of a brain dead donor and of course the increasing burden of kidney disease in India requires two strategies of course one is to prevent CKD but the other strategy is to increase the disease donor organ donation rate. What are the benefits of a disease donor program improve access to transplantation it could break the economic and social barriers of transplantation it could deal with the problem of organ shortage there could be a containment of expenditure will procurement and of course we could generate a trained workforce which which has in its final outcome a presence of dedicated manpower and resources which improves this program overall. Coming to what I mentioned earlier was the extended criteria donor which is called ECD to address a donor pool shortage and water is an ECD or extended criteria donor it is kidneys from a brain dead donor more than 60 years of age or a donor who is 50 to 59 which features like history of hypertension or terminal serum protein more than 1.5 or cerebroscour disease as a cause of death and there has been a significant improvement in survival with ECD kidney especially in older ESRD patients when a living donor is not possible there is no doubt that the survival with ECD kidney is much better when compared to the by the other patients and there is no evidence of higher risk of transplant loss or elevated mortality with ECD kidneys in recipients above 70 years. So an older kidney for an older recipient is a worthwhile idea what are the indications for ECD kidney transplantation or delicious patients whose life expectancy in dialysis is lower patients who have a vascular access problem patients with low immunological risk patients above 40 years of age patients who have been waiting for more than 4 years and patients with diabetes or hypertension. So if you carefully select a potential ECD recipient then you can actually improve the outcome with ECD donors. What are the long term outcomes of transplantation kidney using ECD donors? So this was the article published in BMG 2015. This was a prospective population based cohort evaluating the long term outcomes of transplantation using external criteria donors and as per the data out of the 2,700 transplants done 33% or 900 odd work from ECD donors. It was found that there was lower aligrav survival in patients receiving ECD transplants. The worst survival was seen after 7 years if there was a circulating DSA at the time of transplantation and improved survival was seen if there was seeding was done so that there was an absence of circulating DSA in the potential recipient and if a shorter cold is keemier time of less than 12 hours could be attained. So what were the independent determinants of long term loss, longer cold is keemier time more than 12 hours, circulation of DSA on the data transplantation and allocation of ECD. So how was the ECD allocated? So the aligrav survival after 7 years if you were to compare then ECD transplantation had 80% as compared to 88% for standard criteria donors. So the authors concluded that allocation policies to avoid donor specific antibodies and reduction of cold is keemier time could prevent wider implementation of ECD transplantation in the context of organ shortage. Coming after this section, we come to our next section which is how do we implement a disease donor program in kidney transplantation. So disease donor kidney transplantation has been a success story in the US and how how has it been made a success story. One, the organ allocation could be based on proximity circles from the deceased donor organ. So the cold is keemier time could be reduced because the potential recipient is close to the donor. Then recipient evaluation with a rigorous medical and psychosocial evaluation based on which the patient is put on the wait list, good perioperative care and in the US nearly all the potential recipients for a deceased donor receive induction therapy and of course standard initial maintenance with TAC, amorphous steroid. If you were to see the unadjusted aligrav survival rate and the patient survival rate of deceased donor kidney transplant over 10 years at one year, the aligrav survival is 97% and patient survival is 99% at 5 years 90 and 89 and at 10 years 77 and 75. So with improved utilization of deceased donor which improves the access to kidney transplant even the outcomes are improving. Going to some Indian experience, this is a single center experience published in 2021. So this was a study which assess the various measures taken at a single center level to improve organ donation rate and to analyze the outcome of deceased donor transplant. So the trend in the organ donation was seen over the last decade or so and was found that the biggest jump in the rate of donation happened in 2015 when the number of transplant coordinators increased to 3 and the counseling of the families of potential donors was started in the triage area. So active transplant coordinators and active counseling are two interventions which improve the organ donation rate and a three year analysis of the patient and the graft survival showed that they were around 90% 3% at one year, 89% at two years and 85% approximately at three years for both patient and graft survival which is not bad at all. And this study has demonstrated that steps taken at a single center level alone can significantly improve the deceased donor program rates even without substantial help from the government and what are these steps dedicated to professional including transplant surgery coordinators, a protocol based approach for referral, early counseling in the triage area and regular audits. So these are the four steps which actually improve the organ donation rates. This was the data published which was a DDKT in a tertiary care center by Dr. Mukherjee is group in 2020 and this was again a data from armed forces hospital and they analyzed 92 deceased donor transplants done in a 20 year period and all of these were blood group compatible atchillimatching.done. Induction was IL2 till 2005 and ATG after that and maintenance was cyclosporin MRS steroids initially to run 5 and then check it all in once and all patients received primary, CMV and the pneumocystrophylaxis. The mean graft survival time was 81.6 months and the mean patient survival time was 99.5 months and the bar diagram shows you the cumulative graft and patient survival which was at first year was 98% and at 5 years around 70% of so. So the authors concluded that a satisfactory graft and patients via rate was observed with but the overall contribution was only 1%. Then we have some data from army hospital which was a retrospective study in which patients received rabbit ATG as induction therapy and these it was found that the one year patient survival rate was 92% graft survival and patients were 83%. The delayed graft function was seen in 34% and 16% patients had biopsy proven acute rejection of all of which reverse weight treatment. So again, disease donor kidney transplantation have satisfactory survival rates despite incidents of delayed graft function and of course as mentioned earlier marginal donor kidneys can add to donor pool. So these authors concluded that a reasonably good cold is came at time of 6 hours was achieved by putting as soon as possible whenever there is a declared brain dead 6 to 8 recipients are called cross match is sent and others started and the geology team is divided into both trivial and transplant teams and once the consent is attained the best two suitable cross match recipients are taken to the operation theater. Both the essence is to choose the right recipient and minimize the cold is came at time due to which the delayed graft survival was only 34% also in this study. Then we come to the the Chennai experience which is from see Ramaj another medical college where 68 disease donor kidney transplant performed and the one year and five year patient and also I was 80% and 60% and respectively and they showed that image and large function was established in 50% patients 17% required dialysis because of delayed graft function and acute rejection was seen in 26%. So the authors said that favorable transplant outcomes are achieved by creating the positive public attitude early identification of brain dead donor from consent for organ donation on both hospital infrastructure and good support logistics. So with this background how does one establish a disease donor program? So but what are the promises and challenges for a disease donor program? There's a huge potential for disease organ donation we all know that and a properly organized it can fully cover the organ shortage gap making it a possible alternative to a live transplant program but we all know that the rates are very very low in India and many cultural regions believe influence the disease for organ donation. The most important causes for refusal for organ donation could be lack of awareness in 80% religious beliefs in 63% and lack of faith in the healthcare system which is 40% but I think all of these can be overcome with some degree of effort. What are the drawbacks in the disease donor kidney transplant scenario in India and if you know these drawbacks then you can ensure optimal and better graph survival. If you can go against these drawbacks one is that immunological risk is not assessed properly and regularly in the recipients awaiting transplant. Actually matching is not done in majority of patients awaiting transplant because the patient awaiting for a cadaver organ for maybe 5 to 6 years would not want to spend more money keeping an actual report in pocket when there is no assurance for an organ allocation because these tests expensive. There is a lack of knowledge of price sensitizing the recipient. There may be a lack of nephropetological services for early biopsy diagnosis, lack of low cytometry and lumenex assays for better cross-match assistance and the services like good nephropetology and good immunological facilities may be available only in a few private sector and few flagship government hospitals. So how do you what are the steps of establishing a successful disease donor kidney transplant program? One you need to offer the program the transplant surgery and medications at an affordable rate to all patients and may be free of course to poor patients. There has to be positive support from local government and NGOs. The waiting list has to be transparent. There has to be an adequate hospital infrastructure. There has to be an aggressive donor management before harvesting. There has to be a brief counseling and time and declaration. There has to be a good communication network and of course general population needs to be made good aware of the organ duration and the need. What are the note of guidelines which assist? One medical and nursing team play a major role in obtaining formation for organ donation as many times donors are victims of sudden illness or accident so the family may not be prepared. The transplant center has to be notified as early as possible so that there could be a best possible donor maintenance suitability of donor could be assessed and the surgical teams could be mobilized as early as possible. And what are the criteria for disease to organ donation? Normal renal function? No hypertension? No diabetes? No malignancy? Other than primary brain tumor? Or a treated superficial skin cancer? No generalized viral ability infection? An acceptable urine and negative viral assays. Your potential organ donor has to fulfill all of these criteria with exceptions for the ECD donors. What can be the steps taken to improve outcomes? One donor selection? So an extreme of age, presence of sepsis, diabetes, hypertension could all be excluded. The maintenance immunosuppression has to be standardized and as per the protocols and as per the program, which is the live program, induction agent is generally recommended in all cadabular called disease organ. It could either be induction with ATG or basal exam and tell you the differences in the data available. And of course, the organ allocation has to be as per the waiting list on the state wherever the patient is domiciled So what was the data regarding the need for induction therapy in disease donor kidney transplantation? The logic is that there is an upregulation of immunogenic molecules after brain death or during subsequent procurement of organs. And this previously exposes allografts to acute rejection and delay graph function. And delay graph function majorly is due to the ischemia reperfusion injury. And of course, is more severe in disease donor kidney transplantation. The incidence could be as high as 50% in disease donors, but only 4 to 10% in living donors. And this increases further in extended criteria donor or donation after cardiac death. So if the risk of rejection is higher, then naturally the induction therapy need is higher. And if you were to assess the poor incidence of acute rejection, then you find that it is 49% in patient with delay graph function as compared to 35% in non-rel guard function. So if you expect delayed large function, then definitely these patients deserve good induction therapy. And so this was a study which compared rapid ATG versus no induction. And it was found that the acute rejection rates were 8% in the induction group and 27% in the no induction group. But the patient's arrival was higher in the no induction group. So you have to balance the risk of acute rejection, which was a weight against the risk of infection, death and functioning graph, death with functioning graph in the group which receives induction therapy. This was a study which compared basic Lexi-MAB versus low dose abitatigi, which is 1.5 gram per k-bait per kg body weight, 3 doses. As compared to high dose abitatigi, which is 1.5 gram per kg on more than 4 days. And if you look at the survival curve, the graph survival comparison, you find that the best was seen with low dose ATG as compared to basic Lexi-MAB and there was no advantage of a high dose ATG. So generally a low dose ATG is known to have the best graph survival rate and must be compared as an effective induction agent. What are the lessons learned from a deceased donor program in North India? So this was permission 2016. When a total of 99 brain dead patient identified, always 67 were medically eligible, only 8 families agreed. What were the reasons for negative consent? Lab of consensus among the family members, mistress of the medical system, fears of mutilation of the body and delay in the funeral. And what were the reasons for a positive consent, mass media campaign, good ice shoe care, good rapport with the family and of course a streamlined medical legal process. So what is the road ahead? Increase the prospective donor pool, so target to convert at least 50% of road accidents and then use donor from snake, so patients who die of snake bites, you should have better immunological platforms so that sensitize hosts and the risk of rejection is decreased. The prospective transfer program should be considered allocation may be based on sensitization and of course a robust support is required with a central 24 by 7 help desk or a call center and of course all the support has to be 24 hours, whether a laboratory or an operation theater or surgical team. So what are the key messages from this evening's talk? There exists a large gap between the number of patients waiting for transplant and those who are seen in the transplant and the deceased donor pool may be a potential solution. The pool can be further increased by using extended criteria donors. Efforts are being made to improve the deceased donor donation rate in India and there are success stories like Amda bath and Chennai and Chandigarh, where there is a higher patient in graph survival rates after the deceased donor transplant. Bendy can and nursing teams of course may have a major role along with transplant coordinators as I mentioned and in India, though the potential for deceased organ donation is high, the rate of donation is low almost the lowest in the world which could be attributed to lack of awareness, religious take matter and infrastructure deficiencies all of which could be targeted at multiple levels. With that, I come to the end of this evening's talk. This is a recorded talk. So any queries regarding the talk could be forwarded to the organizers who could then forward it to me and because India will reply back by email or whatever suits the organizers. Thank you so much, Team Sanofi for inviting me for this wonderful talk and I actually myself learned a lot today. Thank you so much.
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