Is anybody a transplant surgeon? No? Great. I'm safe then. So I work at Penn, and it's VA. These are my disclosures, none of which are financial in nature, but I do not speak on behalf of the federal government. I'm sure they would disavow knowledge of me in any way, shape, or form. This is what we're going to talk about. Some common complications principally focused on liver and kidney transplantation. We will group this into technical aspects, infection-related, medication-related, and in particular, what often appears on board exams is the management of those suffering from acute rejection. I like to put these forth as organ agnostic common complications, because it doesn't matter which organ is being transplanted, you will see these kinds of complications. Now you can see I've grouped them here from infection to graft failure to organ failure of a non-grafted organ, endocrine-related issues, and then those that are related to pharmacology. In each of the categories, in the subcategories that you see here, there are standards that you should be aware of in terms of, for instance, graft failure, whether it's acute or chronic, what kind of cell type it is, or is it antibody-mediated. Big things with regard to endocrine in particular are new-onset diabetes, and in certain circumstances, in particular with renal transplantation, new-onset hyperparathyroidism. We will talk about many of these organ agnostic complications throughout our two hours together. Cardiovascular disease is incredibly common. Now what you're looking at on the left, the big bar is any cardiovascular disease after solid organ transplantation. Almost 45% of everyone. All along the bottom are very specific kinds of cardiovascular diseases. That these occur in an accelerated fashion after solid organ transplantation is a testable point. They won't ask you in particular which one, but coronary artery disease predominates by comparison with all the rest. And it is uniquely tied to very common immune suppression regimens, and you will see these. It's commonly, at this point, tachycardiomyosin with mycophenolate and steroids. Those predominate in about two-thirds of all patients that undergo solid organ transplantation for renal failure or hepatic failure. There are some steroid-sparing regimens. There are some that have people off of mycophenolate. But far and away, a three-drug regimen is the most common. Question one, which of the following is the most accurate regarding malignancy risk after solid organ transplantation? The risk is similar to those that have not had a transplant. The risk is increased. There's only increased risk for certain bone marrow cancers, or there is, in fact, a decreased risk of squamous cell malignancy. Who's gonna go with A? B? You got a couple of hands. How about C? D? The answer is, of course, B. When you look at de novo malignancy, and this is now standardized incidence ratios, all organs, all cancer, have almost a three-fold increased risk of de novo malignancy. Squamous predominates. And in fact, if you look at renal versus hepatic, almost half of all people that undergo renal transplantation develop a squamous cancer. So they should have routine dermatologic assessment as one of those routine follow-up kinds of things. It's very testable. There are post-transplant lymphoproliferative disorders. It is highly variable, from one to 20% after all kinds of solid organ transplantation. If you get this, the mortality rate is quite high. It's 50%. It outstrips the mortality rate from ARDS. It is divided into a bimodal distribution. Early is one to two years, late is five to 10 years. And in between 50 and 80% of the early cases, Epstein-Barr virus is the culprit. And therefore, this mandates routine assessment and testing. You will also routinely deal with new-onset diabetes. And what you're looking at are those that did not have preoperative diabetes in orange versus those that have it in black. And what you'll notice is that regardless of what the regimen is, and it's cyclosporine, serolimus, and tacrolimus, they will all induce it. And the two most commonly used immune suppressors, serolimus and tacrolimus, will do it quite rapidly. You're looking at a 10-year span. So when you look at this stuff, you see this goes up quite rapidly and it stays up. This goes up and drops off, often because the agent gets changed, not because they get better. Question two. Patient three months after liver transplantation presents with disordered consciousness, generalized seizure, and hypertension, systolic of 200, but does not have focal findings, nor does this patient demonstrate fever. Which of the following assessments is the most appropriate? How about blood cultures? Right, you don't, no blood cultures? Nobody wants to have, LP. Can't sell that one either. Hepatic ultrasound. Brain MRI. All right, why do you want an MRI? Since you're in the front row and I can see you. Okay. He or she could be on a CNI that causes a press signal. You win, press. Okay, not terribly common. Does not have a fixed timeframe. Decreased level of consciousness. Seizure, visual changes. Severe headache is very common, or severe hypertension is common, but headache is very uncommon. Differentiates them from those that have hypertensive urgency or crisis. You want an MRI with a T2 flare occipital and parietal region focus. Of course, everyone orders it just that way. And if you have it, and you'll see what it looks like, the treatment is to stop, or at least change the immune suppressive agent. And this is what you have. And you can see in the T2 images, all of this is indicative of press and it is reversible. Infection, really common. All the places that you normally think about, except we often forget about primary CNS infection. So you must ask about that as well. It's one of those spaces where everything else is negative and you wait two to three days and you say, well, I'll get a CAT scan of their brain. That looks okay. Now I can do the LP. You should think about this much earlier. Surgical site infection, whether it's superficial or deep or organ space, we all think about very early after organ transplantation, but based on their immune suppression, you can have a very delayed presentation of that as well. And you might not identify that infection until a couple of weeks later, rather than only presenting a couple of days afterwards. Imperatives in your initial post-transplant evaluation. And you see them here. Things that are unique to the donor. Such as infections. Things unique to the recipient. What infections or organ failure do they have? And what happened intraoperatively? Now we think about liver transplantation and if they had more than six units of product, we go, oh, I'm sorry, what happened? But early in the course of liver transplantation, 100 units was not uncommon. You have to think about donor physiology, concomitant infection, organ function. Was this a really good organ to transplant or not? And how was it acquired? Was it a super rapid recovery packed on ice after being flushed with Wisconsin solution? Or were they on a perfusion device? And then what happened intraoperatively? Were there technical problems? Did the graph demonstrate reasonable function? Is the graph really big for that person? And now you have to worry about intradominal hypertension. And what has that patient's allogeneic exposure been? And how is that likely to impact what you assess in terms of graph function? Many pathways to organ procurement. Also many pathways to disaster. Most commonly, brain death by neurologic criteria. You are all familiar with declaring people brain dead. Great. There is increasingly donation after cardiac death. Is there anybody who's not seen donation after cardiac death? Good. There's living related, living unrelated, but increasing there's donation after cardiac death that is supplemented by normothermic regional perfusion. And so basically your brain gets excluded and all the other organs get reperfused using what looks a lot like bypass. And so that you have oxygenated normothermic blood and you have organs that are preserved and therefore they don't need to be rapidly recovered. They can be recovered in a sequenced time-based fashion. So the preservation piece may be important for your graph function. Most of the data supports organs that are transported in a perfused fashion tend to have better outcomes because they have fewer ischemia-related complications. And that gets us into kidneys. If you have not seen kidney transplantation before, the native kidneys remain in place and the new kidney gets placed somewhere in the pelvis. It doesn't matter which fossil you use, the right or the left. This has it depicted on the left, but commonly it's placed on the right to avoid any issues with sigmoid-based adhesions from prior diverticulitis, which is much more common than anyone thought. There are a huge number of technical complications for something that requires three anastomoses, right? Renal artery, renal vein, and the ureter. How hard can it possibly be? And yet, you see all these from stenoses to thromboses to fistulae to collections around the transplanted organ, and of course, some that are related to the quality of the organ that has been procured. Did it come from an 18-year-old or did it come from a 54-year-old who had a long and difficult course? So all of those complications are part of what you get to surveil, and they have a time basis to them, as do the infectious complications. Donor-derived infection is not particularly common, but donors that are infected are suitable for organ donation after about 24 to 48 hours if they demonstrate some signs of clinical improvement. The white count is getting better, the fever curve is improved, and then the recommendation, which is not at all precise, is for seven to 10 days of culture-directed antibiotic therapy after transplantation. None of this will impede CMV and EBV transmission, and therefore, prophylaxis is expected. So in particular, if you have a new transplant fellow and they did not write for that, you need to catch that and make sure that they put them on CMV and EBV prophylaxis. Yes, it's a busy slide. It's busy for a very particularly good reason. The timeframes are important. Within a month, one month to one year, and then more than one year. This is very common for renal transplant infections in terms of how they are divided. And the things that are important to take away from this is that early, you have to worry about nosocomial and donor-derived infections in particular. Over the next year, there are infections that are related to whether they did or did not receive prophylaxis. And after a year, some of the typical opportunistic infections are then what you are concerned about. So it drives the kinds of empiric therapy that you would select. We'll mention that community-acquired infections also remain important after a year, but we worry less about those than we do about the nosocomial infections because all of those have an untoward impact on graft survival and, in fact, patient survival. After you have your transplant, who comes back to the ICU? Not a lot, maybe one in 10. And what they typically need is either invasive ventilation, renal replacement therapy, whether it's intermittent or continuous, and a vasopressor. Most of the time, it's related to acute respiratory failure, shock, acute kidney injury, or coma. It's not other kinds of things. Those are all testable things. I leave this up here not because you don't know this stuff. All of the stuff that are in the boxes are what you routinely do when someone has come in and they've had a renal transplant. We're always working with pharmacy in terms of agent toxicity, but what I really want to call attention to are these other considerations. Avoiding nephrotoxic agents, assessing duplex graft flow and whether it's a collection, modifying medications, and specifically looking for neutropenia. Those are priorities. Hospital readmission, as opposed to ICU admission, occurs in almost half, principally related to the GU system. If they require readmission, much higher rate of allograft loss and an even more outsized impact on survival. Therefore, the way that you monitor patients and the vigor with which you monitor them specifically catch the things that bring them in, like infection and endocrine abnormalities, helps reduce this particular impact. Early versus late renal allograft dysfunction has different causes. Rejection, toxicity, BK virus nephropathy in particular is important, as are some of the technical complications. And later, it's glomerulopathy of the transplanted organ, nuanced glomerulonephritis. Guess what? BK virus doesn't really go away. You have to think about that. And then late arterial stenosis, either related to neo-intimal hyperplasia or some technical aspects that have finally evolved. Hyperacute rejection is one of those unique things that occurs early. And that is from preformed antibody. And that is usually related to screening failure and therefore mismatch. That is not very common. Acute rejection diagnosis and management. It doesn't matter where you are, the ED, the acute care unit or the ICU, antibody mediated in cellular rejection, which is now T cell rejection, is about equally identified. Hyperacute is what you see in the operating room. You put in the graft and then the graft dies. That's the preformed antibody. Doesn't happen very often, acute rejection. It used to be virtually everyone got it and now it's somewhere around 10 to 12%. And this is all based upon the elaboration of new immune suppressive agents. If you have rejection, who's been to Banff, Canada? Anybody? It's lovely, is it not? Did you stay in the hotel? It's a castle. It has many different spaces. It's beautiful. It was moved from one side of the country to the other brick by brick. And it's exactly how they built these guidelines. Individual pieces with different kinds of acute T cell mediated rejection categories with lots of criteria. And so you're not expected to know those criteria, but you are expected to know that there's a guideline and it comes from Banff so that you can decide which one it happens to be. There is linkage of the type and the extent of rejection with therapy. And therefore, there is a treatment algorithm. No, the specifics are not important. These are well published. You can read through these. If you have the patient, I suggest you call it up and look at it. What should I use for this? But it is all driven by, I can't get a biopsy. I can get a biopsy. And therefore, identifying what type of rejection you have using the Banff criteria for biopsy, proven rejection is really helpful. And if not, then you can take a look at blood flow with the digital subtraction angiogram, decide how best to treat that particular patient's rejection. So there is an algorithm for this. Let's move on to the liver, which you have not yet poisoned since there's no alcohol at lunch. You can't also be sad about that. Sparsky, what can I? You just have to be sad. You just have to be sad. That's right. So when you look at all of this, bad liver comes out, new liver goes in. Many more anastomosis. Anticipated that if you're doing it from a donor that is dead, you can do it from a donor that's live, but you only have part of the liver. Lots of complications. I'll draw particular note to those that are related to the biliatory system because those in particular are related to ischemic cholangiopathy, which is much better. It has a lower incidence in dark blue with normothermic regional perfusion by comparison with super rapid recovery. So complications are decreased based upon how you acquire this particular graft. Six weeks after liver transplant, patient develops abdominal pain. LFTs are up, bilirubin's up, the white count is up, the transplant surgeon is up in your grill. Which of the following assessments is most likely to determine the underlying cause? Who wants to biopsy the liver? Blood cultures. Hepatic artery ultrasound. And a HIDA scan. You got a couple of people, it's the hepatic artery ultrasound because you're worried about hepatic artery thrombosis. It's the most common complication. It's even more common in kids. Mortality is very high if you get it because the liver dies. It occurs commonly in the first one to two months, but can occur earlier. Remember, the bile ducts only have a hepatic arterial supply so they will die if they don't have enough flow. And the diagnosis is by duplex. Standard major post-operative priorities, and not listed on here, is making sure the transplant surgeon feels comfortable. You really want to avoid volume overload because that then creates an increase in hepatic venous outflow pressure. And so we talked about that during the Q&A session. Graft dysfunction. Same kind of time frame as what you had for kidneys. And you can see these kinds of complications, vascular biliary leak and infection, predominate early, and then you have all the rest of them that occur over the subsequent time frame. Infection is always an issue, but more than a year, de novo disease becomes very important. New HCV, new alcohol-mediated toxicity. There is a fresh liver, I can start anew. It's true, infectious complications, also divide a little bit differently than kidneys. Transplant to one month, one to six months, more than six months. Same kinds of things where the opportunistic stuff occurs a little bit later than the community stuff. And in the first month, it's all the hospital things that you would think about, including C. diff. Acute rejection diagnosis and management after liver is different. It's like eyeballs. It's an immunologically privileged organ. There is almost no antibody-mediated rejection. It's all T cell. And oddly enough, the presence of T cell rejection does not degrade organ function. So it's a weird organ. There are mechanisms for this. Ignore all the mechanisms. You can look at that later if you wanna parse through all the molecular biology. The therapy is glucocorticoids and rescues almost 85% of people. It occurs early, one to six weeks. Hospital readmission, you're looking at people that are readmitted within 30 days versus 90 days. Doesn't matter in terms of outcome. Does not impact organ function, not one bit. If you have a really long initial hospital stay, that impacts outcome. They tend to have a more rocky road and they have more complications. What drives readmission? Infection is the number one cause. Technical issues, altered mentation are about the same and much more so than acute kidney injury. And most of those are related to medications. And so I'll leave you with three things. Infectious versus non-infectious based on time. Technical issues occur more commonly with liver transplant than renal transplant based upon the number of anastomosis. And the laboratory profile becomes important for you to identify rejection, infection and medication related toxicity. Questions, thoughts or concerns for organ transplantation? Stunned silence, it's like asking my son, what would you like for dinner? Thank you.

transplantation complications

liver and kidney transplant

graft failure

infection control

cardiovascular disease

diagnostic strategies