Kidney and Graft Failure Post-Transplant: Reasons and Strategies for Prevention and Management
Dr. Sagar Gupta, a senior consultant in kidney transplantation at Metro Hospital, Faridabad, introduces key aspects of kidney and graft failure post-transplantation. This educational session explores risk factors, prevention strategies, and management approaches, emphasizing the role of immunosuppression in graft survival.
Key learning objectives include:
- Understanding risk factors and outcomes of kidney and graft failure.
- Strategies for prevention and management.
- The role of anti-thymocyte globulin (ATG) in preventing rejection.
The discussion highlights acute and chronic rejection mechanisms, donor-recipient compatibility, and immunosuppressive balance. Early diagnosis is crucial, as delayed intervention reduces treatment efficacy. Identifying donor-related, recipient-related, and perioperative risk factors helps optimize transplant success.
The session will further explore T-cell and antibody-mediated rejection, their histological classifications, and treatment considerations, ensuring a comprehensive understanding of kidney transplant failure dynamics.
Dr. Sagar Gupta
Hi, hello everyone, my name is Dr. Sagar Gupta. I am a senior consultant in the technology and kidney transplantation at Metro Hospital Faridabad Sector 16a. I did my ambience from Malana's Abh medical college after that I did my residency, kidney transplant, nephrology and kidney transplant fellowship from the US and American Board certified. Today we are going to talk about kidney and graft failure post kidney transplantation, what are the reasons and what are the strategies to prevent it and how to be managed. Thank you everyone for taking out your valuable time and you know, listen to this. We will start with kidney and graft failure post transplantation. So this is just an educational activity and you know, we again recommend that we use your useful, judicious, you know, prescribing information before prescribing any product to the general outline and mention some things. So the learning objectives for today's talk are going to be we want to get an overview of risk factors and outcomes of kidney and graft failure post transplant. Then we understand the strategies for prevention and management of post transplant kidney failure and then lastly we will discuss the understand the role of ATG or the anti-timacyclobulin in the prevention of post transplant kidney failure. In the first part we are going to talk about, you know, the general aspects of kidney and graft failure post transplant. Basically, the patients who develop chronic alograft dysfunction and graft failure due to insufficient immuno suppression or medication non-adaren. Those are the two most like, you know, common things what lead to rejection. We will come later on to acute and chronic different kinds of rejection but basically insufficient immuno suppression or medication non-adaren. Those are the two most important reasons why patients get into chronic alograft dysfunction and chronic AMR and which leads to graft failure. There are certain studies that tell us that there is a three-fold higher mortality rate than that before graft loss in patients returning to dialysis after graft loss. The incidence of acute rejection is usually 15.2% and the chronic ranges from 20 to 40%. 4 to 5% of the incidence dialysis population is with a failed kidney autograph. Again, this data may or may not be very true for India but those are general numbers we have seen. So, I'm sure all of us are aware that rejection if you classify it in terms of it can be either one hyper acute or it can be acute or it can be chronic. When you talk about the histological types, it can be either T cell, antibody mediated. So cellular and antibody mediated. Those are the two histological types. The donor kidney being an alloy antigen can induce an immune response in the recipient. If this response is not controlled, it will destroy the graft and this is called allograft rejection. So, that is a very simple explanation of what is rejection, what is going on. Basically, the patient or the recipient's immune system mounts the response against a form of object which is the allograft. Different mechanisms that lead to different forms of rejection. So, when you talk about acute rejection, it basically means abrupt onset of allograft dysfunction. It is experienced by approximately 10% of patients within first three months after transplant. We have made some significant improvement in these numbers I would say. In the era of no induction, we saw rates as high as 40, 45%. Then we came down to 20 to 25%. And now we are down to 10 to 16% on an average. The numbers have reached single digits lately in many subset of population. Chronic rejection basically means slow allograft dysfunction. The incidence is approximately 1.4 for 25%. In suppression, the immunosuppression predisposes to acute cellular rejection and the chronic diesel mediated rejection. It will also predispose you to antibody mediated rejection, both acute and chronic. Like I mentioned, when you talk about rejection in terms of timing, hyper acute rejection, it occurs minutes after transplant due to preformed antibody or ABO incompatibility. Let me tell you, in today's age, when we have decent technology like the CDC cross match, the pro class match, depending on your institute's protocol, if you are getting a pre-transplant DSA or a donor system with antibody done, the incidence of hyper acute rejection has widely decreased across almost all center of the entire world. But still, rarely the people who will do enough, like 1 in 3, 400, you might see one hyper acute rejection. In my career of 10 to almost what? Well, in 10 years now, I've seen two hyper acute rejections, both are good in actually living related kidney transplants. And we lost the graft right after, and we had to do a graft nephrectomy next day for both patients. When you do the graft nephrectomy and see the histology, you'll see like widespread cortical necrotors in such patients. So this is called hyper acute rejection. In some cases, but kidney turns kind of blue on the table. It can occur minutes after transplant right after you do the mass smoking. Anytime within days to weeks, it's called acute and more than three months, we call it chronic. So as a transplant nephrologist, as a clinician, it is our job to identify what is causing the graft failure. And if the graft failure has started or when has it started, and you know, how to halt, how to monitor and how to halt the progression. So your usual markers, you know, your creatinine, histadency, if you're sent to doing it, that will hint you towards that decline in GFR. So if there's a progressive decline over time, if your creatinine has taken a acute or a chronic jump, you need to evaluate all of the causes and then make sure you keep rejection in mind. The proteinuria can be seen, which you know, a strong correlation between one to three month proteinuria, every 0.1 gram per day in three with graft loss. So make sure you know you get your urine routine, your protein plate and your ratio. They'll also help you with picking up the recurrence of original disease early. The reason we need to pick up your graft failure quick and early is because the more the delay in diagnosing rejection, the lesser of the chances that it is going to respond to your treatment. So when you have decreased kidney function associated with an increased risk of all cause mortality also. Because like I mentioned, there's a 54% higher mortality in transplant risk experience. The reason is they are already on immunosuppression. We are trying to win that immunosuppression of poor graft function associated with long-term post transplant death in graft loss and highest risk of mortality than the first year after returning to dialysis. So when you talk about the risk factors for rejection, like what are the risk factors in general? So multiple factors govern graft rejection and graft loss after kidney transplantation. So with like I said, we need to keep in mind the factor so that we can identify these risk factors early and avoid some optimal organ allocation to begin with and then we can improve the short and long outcome of kidney transplant. The first set of factors is donor related, the second set of factors is recipient related, the third might be donor recipient compatibility issues and then after that we have pre-operative and post-operative factors. When you talk about the donor related factors, the things that count are gender, age, living versus diffuse donor, non-marginal and marginal donors. A lot of these terms are applicable to like diffuse donor transplantation only. When you talk about the recipient related factors, it's race, age, concomitant diseases, retransplantation. All of us know, younger patients have a more robust immune system, so younger the patient higher the chances of rejection. When you talk about race, certain racial subgroups like African Americans are more predisposed and now we have already found out a lot of genetic causes also that might be predisposing them to their increased risk of rejection. Concomitant diseases like there could be factors where inflammation might actually cause increased antigen exposure and hence lead to rejection. And then retransplantation once you've already had a transplant done. So the problem is you already have a set of exposure to antigens and your body will make a pre-formed set of donor specific antigens. So retransplant is always immunologically higher risk phenomena. When you talk about the donor recipient compatibility things, then the ado blood types and woman liquefied antigen typing, those are the two things that make a significant difference. We all know about HLA ABDR matching, which is the basic X out of six matching AB or DR. You can extend it to DPDQ matching or C subtype also that can tell you more if you have a lot of pre-formed anti-HLA antibodies in those cases. We try to look at all the 12 antigens. After that, when we're talking about ischemia, the pre-op factor, the post-op factor, in the pre-op factor, we have ischemia reperfusion injury. So basically all of us know, like the first thing that actually parts of an immune response is the surgical stress, the stress of surgical cutting, the tissue damage, that is which exposure to antigens more and that is the reason we need induction immunosuppression to begin off. Then the ischemia reperfusion injury also predisposes off to rejection and then we have delayed graft function, which can happen depending on a lot of factors and then comes the immunosuppressive regimen. So I think all of us understand that kidney transplantation is walking a thin line, it's a delicate balance. Too much immunosuppression is going to cause infections. Too little immunosuppression is going to cause rejection. Like I mentioned, all these are multiple factors that you have to keep in mind. The main things I would say, HLA, I mean, age, race, if it's a retransplant or not, and then you're actually matching. Most of those are the most common things, you know, that should be on the top of your list. When you talk about like other factors, then time on dialysis, donor age, expanded criteria, donors, received donor, prolonged cold ischemia, immunosuppression, nephrotoxicity, infection, cancer, PTLD. Most of you also have to keep those in mind to make sure, you know, while deciding here immunosuppression regimen. The other thing is when you're talking about a non-alloy immune, HLA incompatibility, donor spheic antibodies, delayed graft function, immunosuppression, non-adaren, under immunosuppression, chronic rejection, acute rejection, recurrent or D-noble GN. All these things are going to predeforce to risk factors. For example, anybody who's had an acute rejection, there are many studies and much data to show that ultimately, even if their kidney function recovers, they are at much higher risk of getting a chronic rejection and their life of alograft might reduce. So these are all the factors that the transplant deforlices are a practicing inclination should keep in mind while those in your immunoprepive drugs. So in the next section, we're going to talk about T-cell mediated rejection, antibody mediated rejection, infection mediated kidney and graft failure, because all those are equally important factors. So when you talk about incidences of T-cell mediated and antibody mediated rejection and kidney transplantation, ABMR is the most common type of rejection, almost accounting for 40% and this can be seen as early as few days. We've seen florid AMRs happening at day, even three, four onwards, that there could be a combination of the two. A lot of biopsies show that and approximately one-third of the rejection could be a combination of AMR and T-cell mediated rejection. While the T-cell rejection, like I mentioned in the beginning, their incidence of going down with a nice use of induction immunosuppression agents, and that has almost come down to 10-15%. So when you talk about the pathogenesis of acute T-cell or acute cellular rejection, the T-cell mediated rejection where Cp and lymphocyte become activated by recognition of foreign donor antigen in the transplant organ, the fleets to activation and infiltration of T-cells, which damages the alograft. When you look at the histology, there's diffused lymphocytic infiltration in the cubioentrustation of the kidney and in severe cases, even vessels of the alograft. When we were students, nephrology training, we used to write down how cellular rejection, how you're going to classify it, one, ABC, two-way, two-way, and if you have vessel involvement, that's solvent into way and higher, because these are things that you should remember at any given point if you're a transplant nephrologist, because these are things that help you take decisions for treatment, because like I said, if you are in cellular class 2A or B, in those cases, you should, apart from doing cortical steroids, keep in mind that you should use anti-climacyte globulin for such cases also. So again, the histological classification or what all points you need to see, that is also very important when you're treating chronic AMR, what is the acute component, what is the chronic component? So like I mentioned, when you're talking about cellular or the QT-cell mediated rejection, we're talking about acute hair. So when you talk about type 1 or borderline, it is just tubular interstitial rejection, you can have like an infiltration of activated helium-cocizant microcosms into a edimatous interstitial lesion. This is accompanied by interstitial edema and sometimes even hemorrhage. The infiltrate is typically patchy in the cortex as well as medulla. Your transplant pathologist is going to give you rating in terms of IAT, basically it's involving how much of the interstitial mentivutes, percentages are involved, that's what they have grade, the histology on. Glomidol lesions, the glomid ligand show minor changes of use, started mono-nupia cells and then segmental endothelial damage. Severe lesions, you're going to see hypercellularity, injury and enlargement of endothelial cells. When there is vessel involvement, you know, the first thing you need to make sure you have an artery in your biopsy. So end-art right-desk or type 2 rejection, characterized by infiltration of mono-nupia cells under arterial and arteriolar endothelium, that would classify us to wear higher. So basically there are certain atypical rejection syndromes which need to be kept in mind while you are dealing with such patients. These are unique patterns of rejection under novel immunosuppression regimens. The relatively preserved renal function in simultaneous bone marrow and kidney transplant can also be seen. When you, the differential we need to keep in mind our cellular or T cell mediated versus the anitoxicity, basically there is diffused interstitial mono-nupia cell in interlutrate versus focal mono-nupia cell in interlutrate. When you talk about interstitial mono-nupia inflammation and tubulitis, you can see this in many other conditions. For example, a small thing is if the infiltrative neutrophilic, you want to keep the differential plus infection like in a developing country like India where we are practicing always in mind and make sure you are not dealing with an active infection also. Abundant eosinophil than usual for rejection and identification of eosinophil has been leading to views, indicates drug allergy, overrejection. So basically you need to keep in mind like an acute interstitial nephritis. You of course get your infection work up and make sure that you are in culture. Negatives always make sure you are now like even if it is a transplant kidney, all the normal causes, pre-dional, renal, intra-vinal, how you deal in general nephrology, all those things are applicable to the alograft also. One way my teacher used to put it is just keep it like a normal kidney, pre-dional, renal post-phenal and add on top of it, rejection infection, BK and CMD. They are your transplant nephrology, you know, mantra in one line. So you need to be good and crisp with your general nephrology where pre-entra-renal and post-phenal. All those causes and reasons are the same for alograft dysfunction and on top of it, you are dealing with this infection, rejection, BK, very useful. So when you talk about causes and issues of antibody mediated detection, AMR is a form of renal alograft rejection due to damage by circulating antibodies that react to donor and aloe antigens per endothelium. The main risk factor for DFA are blood, this happens more when it's DFA. The risk factors are blood transfusions, always inquire your patient when they come for first evaluation, how many blood transfusions have they received in a lifetime. Pregnancy, this was a view for an antigen and then sometimes, you know, infections too. Antigens for AMR, you know, you've got to keep in mind you're at a chili class. One in two antigens, I already talked about it, ABC, DPD, QDR, the main one, ABO blood group antigens. If you're dealing with an ABO and compatible transplant, it's a whole different ballgame altogether. The average factor, you know, most people are, you know, almost all of us don't pay that much attention. But in the transplantation, the ABO and compatible is a different, I would say, signs them almost to certain degree in art. Then there you could have other non-MHC antigens like Nikkei, Nikkei, Nikkei. The diagnostic criteria, there is histological evidence of acute injury, evidence of antibody interaction with tissue and then serological evidence of circulating antibodies. You need to have diagnostic criteria for all three categories. When you talk about the histological evidence, you can see even the ADN, focal necrosis, little mononuclear cell tubulitis, nephrolic tubulitis, mononuclear and arthritis, failure edema, increased intercoron production. The C40 deposition is a specific thing and that is a marker of antibody interaction with the tissue. This C40 positivity can be seen in cases of lupus or ABO incompatibility to begin with. But if your kidney alograft is not ABO incompatible, then C40 deposition is usually considered pathologic. It is kind of specific 96% and 10% of 95% marker of circulating antidone or HLS-specific antibodies. The severity of histological injury varies by antibody with BSN-Q, the moral rejection. BTSA is the serological evidence of circulating antibodies, the third criteria. When you talk about immunosuppression, if you even have suppressed too much, it's a problem because you then run into infection. If you've suppressed too little, then it's a problem you run into rejection. When we're talking about incidence of infection in kidney transplant recipient, the kidney transplant recipients are at lower risk for primary CMB infection compared with other organ transplant recipients, mainly because kidney is the most widespread studied organ. In a lot of good centers, we find a master, I won't call it master, we are far from mastering. We have kind of become in better day by day in using a CMB prophylaxis, not immunosuppressing, but drawing your antimatter blood, things like that. The incidence of infection with a specific 0.2 per 100 patient two years, post transplant in Canada. I was trained in the US, but after coming to India, I realized, all of a sudden, this kind of infection was higher here. And that is the big reason, I think, our patients, we have to tailor our immunosuppression regimen according to the Indian patients, watch them very closely, try to make sure they don't run into too much infections. The CMB infection rates could be anywhere from 10 to 32% EBB low, FV, VV, common depending on the prior exposure and rates, BK are getting up to 1 to 10%. I think again, with our monitoring, you know, preemptive monitoring and things like that, BK has also kind of gone down. When you talk about bacterial infections, it could be up to 50%. The surgical wound infection rate could be anywhere from 3 to 4% to higher one, depending on the area you are practicing and things like no cardiac, pretty uncommon. So when you talk about the Indian recipient, I just kind of gave a brief overview of that also. Red respective study showed that 11.7% of patients had an infection within one month, whereas 68.4% of patients had at least one infection episode within the first six months. So you can imagine almost one out of 10 or one out of eight, one out of eight is what? 12.5% they will have an acute infection in one month and over two-thirds of people will have an infection in six months. You can see the rate of infection is a lot higher. You need to keep in mind back TD, CB, viral, lungal infections. I had to learn my tuberculosis and kidney transplant things in India after coming back because you don't see that too commonly in the developed world. Red respective study showed that the prevalence of clinical irrelevant infections after KDP is widespread and like I mentioned bacterial, fungal is also pretty common in the others. You could really have donor-derived infections. I've personally seen one case. I cannot delve into too much detail, but basically the mother had an impacted stone and she was probably in a chronic pile on a fight, a kind of a state. The family was counseled by the doctor who did the transplantation. Father said no to donate, so the mother said, okay, save my child and then she donated. But then post transplant with immunocompression, even though his mother was okay, she never had fever, chills with urea, anything. The recipient went into a florid, pile on a frite, a graph, fly on a frite and they lost the graph quite early. So you could have a donor-derived infection. The other things possibly are virus, bacteria, fungus, parasites. The recipient-derived could be like a said, PB, strong-glued, viral, histroplasma, porcidio, parapoxidio. Community-derived exposure include MRF, VRE, CRE and ESVL, fungus, like a purgeillif, and non-alkricant candidate species. No, you want your patients to have a good quality of life and return to work. They could have foodborne and waterborne infection, respiratory virus, common cold, the individual pathogens, the graphical restricted fungus and parafides, amoeba, and then let's not forget the good old COVID. So basically the nosocomial technical donor-derived, recipient-derived is usually less than four weeks and it is MRF and Candida, VRE, Espergillis, Apparation, C-DIP. When you talk about opportunistic relapse or residual activation of latent infection, it could be anywhere from one to twelve months. Then you have community-coid infection, which can occur anytime, but they are more common after twelve months. Infection after transplant tends to occur in a predictable pattern based on the immunologic exposure of the host and nature of immune deficits, patient-with-infection falling outside the usual pattern such as unusual exposure or excessive immunofurgression. When you talk about selected infections of important spectrum of infections with broad, I've seen a patient, the big thing is crypto, so we had a cryptococal infection. He came in quite sick. He had a cryptococal pneumonia. He had CNS involvement in the form of cryptococal meningitis. He had joint pains, weight loss, low rate fever. So, you know, we don't think this applies to my cryptocogus. You're going to see those if you're dealing with enough patients. You're going to see all those complications. It might be less than, you know, five percent, one percent, two percent, but still. Given the potential toxicity of antimicrobial agents and the need for rapid interruption of infection, early specific diagnosis is important. Initial lympharic therapy is broad, and then you rapidly narrow it down depending on your microbe involved. When you talk about viral pathogens, then you're not transplant required an aggressive pre-conditioning protocol because of CMV or polyoma. CMV and BK are the most common causes of viral infection that can also damage your allografts. CMV, you could see, you know, even pneumonitis, deranged LFT. You need to check the patient's serostatas by checking the CMV, IgG. If the recipient is seropositive, in most cases, if you're using a lethal depleting agent as an induction agent, you basically give them 100 days of prophylaxis. If they're seronegative, you should give at least 200 days. There are also a lot of studies done which actually show that the rate of CMV active clinical infection, that is highest, upper, you've just withdrawn your CMV prophylaxis. So, you know, there are studies like if it was an ideal world, you know, valium cycle was expensive, and it can have its own side effects. But if an ideal world was there, you know, you could extend CMV prophylaxis longer to even further take the CMV infection down. The other respiratory viruses like influenza, RSV COVID-19 can result in severe infections. You know, people have gone on to ventilators because of that. And then let's not forget the wrath of COVID that we all saw from 20 in the last three years, you know, the nightmaid we saw, some of our patients, they came out quite well. Some of them were quite sick. We couldn't even save them. We had patients with mucer, post-sterivive for COVID, they seen it all. EBV infection, you're going to affect the b-limfopite. It can call the mononucleosis type syndrome and b-limfopitosis. HPV infection is associated with anal genital and skin precancer, cancer, and waltz. Successful organ transplantation in HIV-infected individuals has been achieved with effective anti-retroviral therapy, anti-minus suppression. J.C. polyoma infection is uncommon in transplant recipients, which may present with focal neural logical deficits or seizures. I don't know, like the newer aggressive approaches out there where they say that, okay, if you're living in a severely organ shortage geographical area, you can even consider doing a transplant from a hepatitis C positive donor. You counsel the recipient that's okay with the use of direct acting antivirals now. The rate of HPV cure is beyond 95%. Some people just take the risk of that 5% or less and they want to come off dialysis and get the transplant done. That has been proposed. In certain countries that are even proposing HIV to HIV positive kidney transplants, that is also possible. It's a risk versus benefit kind of a thing you have to weigh on. In various congregal infections are period stress and all this can affect your breast arrival. The most common fungal pathogen is usually Candida, but like I mentioned, we've all seen histoplasma, pyrgillus, cryptococal patients. I saw last year I was telling you about cryptococal CNS involvement. We even added 5F2, like blue side of things with amphotericin B. That's what we treated him with for a good three weeks and then we have him on a suppressive immune suppression regimen. I think I had him on itro or warring for almost a total of nine months. UTIs are quite common in the first year after transplant and then UTI beyond six months are associated with reduced renal graft survival and increased mortality. So again, you have to keep them in mind. So bacterial, all the bacteria can be seen. We've seen equilient terrovactors, pseudomonas, clipp, and you know, even gram positive, interococal species. You could then have microplause, pneumonia, and lokhardia. We've seen active tuberculosis after kidney transplantation, six months, one year after. So all those things, you need to see where you are practicing what is the epidemiology of infections and then keep in mind all these. So what actually happens when you run into a rejection? When you talk about management of AMR, then the initial treatment usually is, you know, you give them some steroids. Then again, the changing paradigm is too much steroid-related fight in sections later on. So don't overdo it. You need to have an experience or see in your institute region what kind of steroid regimen you want. After that, you know, once you send your samples out for DFA, you can start your plasma for research and then you can give IVIG at the end because it already binds to the pre-form antibodies. Then there is, if you're not getting enough benefit, you need to keep in mind all your armour, retuximab, vortizomeb, time of ATG, or on the eculizumab. So all these molecules, retuximab, vortizomeb, time of globulin or anti- timeside globulin or plzimab have been started in various K-supports, K-series. And again, you know, you have these are all the way, I look at them as these are double edge swords. They will have their own set of side effects. This is, you know, heavy armour. You need to be trained and you need to have seen enough to use all this, when to use, which when you are already dealing with AMR and if it's persistent or non-responsive, you have to increase your maintenance immunosuppression also. Some people have recommended long term therapy with IVIG and you know, again, like I mentioned, you need to be trained and use the folders. When you talk about T-cell mediated direction, the subclinical borderline, sometimes you don't even steroid them like no therapies required. You can just increase the maintenance immunosuppression a little. The reason is that a lot of centers, they still do protocol biopsies and sometimes they see in a subclinical borderline rejection and they don't know what to do with it. The only thing they can derive out of that is increase your baseline immunosuppression. When you're talking about clinical or borderline rejection, then you increase your maintain and treatment suppression and then you give them oral or IV pulse steroids. Usually, you know, there's no fixed protocol. I've seen different people do it differently. If it does two borderline, you can get away with even oral steroids like 40 MG, Omnicotyl. For the first five days and 20 then 10, you can get away with that. Some people when they see a rejection, they just kind of pulse heavily, solumidrol 500 once a day into three days. You know, again, the practice is variable and it's widespread. In many patients, they are personally done just like one gram and left them on vivolone or Omnicotyl 20 with alpine slum. The pulse was just one gram. I think they came out well because too much steroid again will invite infections later on. When you're dealing with a greater than one A, then 250 to 500 into three days with a variable taper like it just mentioned. And if they have steroid resistance to weigh or higher, in those cases, you should consider using anti-phyclobulin. What is appropriate dose while nobody knows, you know, good and bad part about the renal world is a lot of things are not standardized, you know. And I think it is the beauty of good clinician to keep those things in mind and know all the evidence and not just to like one thing in their mind because a lot of the time you have to taper your management according to the what you call the patient and specific scenario. Like I mentioned before, you know, the kidney again, prerenal, renal pose, renal is what you have to keep in mind. Same way you need to keep all the CKD things in your mind, hypertension, protein urea, anemia, and decipidemia management to do the same stuff, low thawal diet, ASARBs, you know, CCBs. If you have your protein urea, make sure you ASARB. And I think we need more data coming out than ASG to enable your dose for transplantation. For anemia, make sure you are using your iron and as it's reported by then for a decipidemia nutrition counseling weight loss statin. And you need to keep in mind your renal loss for this. So, here's the CKD bone mineral disease thing, calcium, phosphorus, vitamin D, PTH, target, HV1C, metabolic acidosis, and other like smoking obesity in the suppression adherence to the disease. And you need to keep in mind your immune disease. And you need to keep in mind your immune disease. And you need to keep in mind your immune disease. 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So that stretch has finally been in your immune disease. And you need to keep in mind well what it is which you have to make in mind your immune disease layer makes you think you need to keep in mind well can you keep in mind well the risk has come on. And that makes you feel better for scientists understand our immune disease and that makes you feel better about having a time. They seem to be conversationally changing Sounds slide would be a substantial number of patients develop chronic allographic function and graph failure due to the insuffining diminished suppression or medication non-adherence. The risk factor include both on the donor side, the recipient side and then in very operative and postoperative monitoring. The risk factors are the same how you manage your chronic kidney disease or CKD patients, hypertension, protein, ure, anemia, dyspeding, and diabetics, fundamental disorder. We need a aggressive preconditioning protocol, but you need to keep in mind CMB and BK at the same time. And then invasive fungal infections are a period spread to both the patient and the graft survival, Canada being one of the most common, but yet histogram, so those are things you need to keep in mind. And then intraoperative modus dose ATG followed by daily load of ATG is safe and very effective and that is one of the best things we have had in advancement in kidney transplantation lately. So that is all pretty much from my side. I again, thank you all the folks who took out their valuable time to listen to this. And I hope you know we gained something out of the talk. If there are any questions or concerns, you can shoot me a quick email at SGNetrology at gmail.com and that will be all from my side. Thank you.
