Transcript
PLEASE NOTE: While an effort has been made to correct errors in this AI-generated transcript, some mistakes may have been missed by the non-clinician moderator. This transcript should be taken merely as supporting material to the podcast and not as an authoritative review.
MIC CAVAZZINI: Welcome to another Pomegranate Case Report, a passion project from Trainees of the Royal Australasian College of Physicians. Dr Stephen Bacchi and Dr Amit Singh are both at the Lyell McEwin Hospital in Adelaide, where they interviewed consultant nephrologist Dr Chiang Lee. A couple of years ago, Dr Lee attended to a female patient presenting with dull abdominal pain of sudden onset. Getting to the diagnosis was quite a process of elimination, and has been written up in the August 2022 edition of Case Reports in Nephrology. But no spoilers just yet. See how you go at following the exposition. Dr Bacchi will lead the way.
STEPHEN BACCHI: Thank you for joining us. My name's Stephen. I'm a neurology registrar at the Lyal McEwin Hospital and today with me, I've got Dr Chiang Lee, who's a general nephrologist at the northern Adelaide Local Health Network. He's passionate about improving the outcomes in patients with kidney disease and has a special interest in chronic kidney disease and dialysis.
CHIANG LEE: Thank you so much Stephen for having me.
STEPHEN BACCHI: And with us we also have Dr Amit Singh, who's a Basic Physician Trainee, also at the Lyell McEwin Hospital. Thanks for joining us.
AMIT SINGH: Thank you.
STEPHEN BACCHI: So, as previously, we'll be discussing a previously published case report in a step-by-step manner, with a focus on content that is relevant to trainees and a generalist audience. So, in this case we have a 32-year-old female with a history of simultaneous pancreas kidney transplant for type 1 diabetes two years prior to the presentation.
Prior to even reaching the presenting complaint in this instance, Doctor Lee, could you please discuss some of the general themes that are necessary to know regarding a renal transplant patient when meeting them for the first time, as if in a long case for a basic physician trainee? And what about pancreas kidney transplants as well?
CHIANG LEE: Thanks, Stephen. That's a great question to start with. Generally, you know when you're dealing with a renal long case and particularly a renal transplant case, I think as long as you approach this in a very systematic manner, you should be fine. What I tend to do is I, I split this into the pre-transplantation phase as well as the subsequent transplantation period. And in terms of what you look at or what I tend to focus in the pre-transplantation period is, it will be very important to know what the aetiology of the end stage renal disease because it will obviously impact on disease progression or possibility of a disease recurrence when you're dealing with a post-transplant patient.
And it would be good to know (1) what the initial presentation was (2) how was it diagnosed (3) what was done to diagnose that (4) whether the renal biopsy was performed; And nowadays genetic testing—whether or not that was performed as well, and also evaluating the risk factors for chronic kidney disease or end stage renal failure; Any previous history of diabetes, hypertension, genetic predisposition, family history of polycystic kidney disease, Alport syndrome, I think that those would be important; And also the duration of dialysis, if there was any prior to transplantation and whether or not they've got any functioning vascular access, i.e. a fistula.
In terms of once they've had a transplant, things that will be important to take note is whether or not it was a disease-donor transplant, live-donor transplant. Some patients may be able to tell you what the matching is, in terms of the HLA mismatches, CMV, EBV status, if known . And also what the induction agent that has been received and obviously the immunosuppression they're on.
Generally, when you're dealing with a renal transplant patient, the backbone of immunosuppression consists of a glucocorticoid, a calcineurin inhibitor as well as an antimetabolite such as mycophenolate mofetil - or equivalent. And so those will be the starting. And once you've had that, I would also evaluate the complications of the transplantation. So, you have immediate complications such as delayed graft function, whether or not the patient required a period of dialysis immediately after transplant, which is more prevalent in patients who receives a deceased or a cardiac death donor. Any rejection, any mechanical complication requiring return to theatre and delayed complications such as rejection, infection, malignancy.
I would also explore the complications from the immunosuppression themself. I will also focus into the prophylaxis for infections such as any PJP or pneumocystis jirovecii pneumonia prophylaxis, CMV prophylaxis and immunisation, in particular, COVID vaccine or shingles. Other preventative health that should be focused in the transplant case is also malignancy screening and bone health. And what is important subsequently is also the progress of the transplant status at this stage. Some patients that you'd see in the long case may have had previous kidney transplants so, it will be important to clarify when was the transplant? How long did it last? What was the reason for graft dysfunction? Whether or not was it rejection or recurrence of the primary disease?
And in particular respect to a pancreas kidney transplant, what is important whether or not the patient received a simultaneous pancreas-kidney transplant or did they receive a pancreas after kidney transplant. And in particular for a pancreas transplant, you need to ask about the glycaemic control, because that's an indicator of the pancreas graft function and whether or not there has been any complications such as pancreatitis, any vascular complication of rejection.
AMIT SINGH: Okay. That's very interesting. So this patient actually had a 3 out of 6 human leukocyte antigen mismatch and her baseline creatinine that was 85 micromoles. She had no history of rejection or pancreatitis otherwise she had a history of urinary tract infections, migraine and left optic nerve changes with an MRI two days before presentation. I won't go through all the medications, but she was taking mycophenolate mofetil, 750 milligrammes twice daily; tacrolimus, 3 milligrammes, twice daily; and prednisolone, 10 milligrammes once daily.
In this case, our patient had presented with abdominal pain, which was constant and dull and sudden in onset there was fever, nausea and vomiting without change in her bowel habits or urinary symptoms. So, while the renal transplant patient can go very well and have, say, appendicitis, and we will consider all relevant routine abdominal pain, differential diagnoses, are there any particular diagnosis that you need to consider more so in a renal transplant patient and does this change with the concurrent pancreas transplant?
CHIANG LEE: Yes good question, as well. While the differential diagnosis for abdominal pain is pretty much similar when dealing with a transplant recipient compared to the general population. But a few things that should be paid attention to is if they there is pain over where the renal allograft is located. A few differential diagnosis should come to mind. One of these is infection such as a transplant-graft pyelonephritis and usually this will be supported by symptoms of fever, dysuria frequency, cloudy urine with supportive biochemistry as well, so you know blood testing and culture results. Radiographic findings are not often very specific, but things that you might find in ultrasound for example or CT, would include a paranephric stranding.
The other differential diagnosis that should be considered is obviously a transplant graft rejection. You need a supportive history where there is a suspicion of whether or not there's a non-compliance with the medications along with elevated serum creatinine or presence of haemoproteinuria, or even a subtherapeutic immunosuppressive drug level. And supportive features would be any positive donor specific antibodies and plus/minus a biopsy result. And usually the biopsy is required to confirm a rejection. The other differential diagnosis will also include any mechanical complications such as obstructive uropathy or collection. In terms of a pancreas graft transplant, pancreatitis would obviously come to mind when you're dealing with a patient with abdominal pain and the differential diagnosis of pancreatitis, which I'll explain later will include infection, rejection as well as vascular complications.
STEPHEN BACCHI: Great, thanks, Dr Lee. In this case, physical examination demonstrated hypotension with a blood pressure of 90 systolic and a sinus tachycardia with a heart rate of 100 beats per minute and temperature of 34.3 degrees. Sorry, let me say that again. In this case, physical examination demonstrate hypotension with a blood pressure of 90 systolic, a sinus tachycardia with a heart rate of 100, and a temperature of 34.3 degrees. Examination only demonstrated tenderness over the pancreatic graft. Initial investigations included a blood glucose level of 6.7, arterial blood gas with a lactate of 3.2, a urine beta-HCG that was negative, white cell count of 22 and an acute kidney injury with a creatinine of 159. Liver function tests were normal and the lipase returned at 3268. An abdominal CT showed inflammatory changes suggestive of graft pancreatitis. Well, that lipase and CT certainly provides us with some direction in this case of abdominal pain. How would you approach the work up and management of graph pancreatitis?
CHIANG LEE: Yeah. So when you dealing with acute pancreatitis, a few differential diagnosis that come to mind are gallstone pancreatitis; ethanol; trauma steroids; mumps; autoimmune diseases; post ERCP or certain medications such as immunosuppression such as azathioprine; the disease-modifying agents such as leflunomide; antimicrobials can also be a cause and even anti diabetic medications such as cetoglyptine exenatide.
However, graft pancreatitis, the differential diagnosis is a little different. Obviously it would depend on the time frame following transplantation and generally is divided into acute or chronic. So, the acute graft pancreatitis most often tend to be physiological due to reperfusion injury that happens within the first 30 minutes or 72 hours. And early graft pancreatitis happens within the first three months and it could be due to infection such as CMV infection, surgical causes or rejection.
The late acute graft pancreatitis would also involve infections, rejection, and vascular supply issues or mechanical causes. So, the approach for this involves taking a good and thorough history; physical examination with supplemental investigations; named the biochemistry lipid studies lipase amylase; and in this particular case, blood sugar level; C peptide level will be important; doing drug levels; virology testing and also sending off sera to check for donor specific antibodies and imaging.
In terms of rejection, in particularr when dealing with a pancreas graft usually there is a degree of clinical suspicion when you're dealing with this, and other supportive findings would involve impaired graft function, elevated lipase, a low drug level and a positive donor specific antibody. Obviously, the gold standard is by performing a pancreas graft biopsy to confirm rejection. And the histological classification is based on the Banff criteria and that usually tells us whether we're dealing with antibody-mediated rejection. T cell-mediated rejection or both. And the treatment when dealing with rejection generally involves intensifying the immunosuppression with the aim to basically dampen or reduce or eliminate the ongoing rejection activity and to prevent further graft damage. Other management for acute pancreatitis obviously would also involve supportive measures such as hydration, analgesia and gut rest.
AMIT SINGH: Thank you for that, Dr Lee. So, empiric antibiotics were commenced during the workup and then she was managed conservatively and showed marked improvement. Rejection was considered unlikely after this improvement with normal C peptide levels and therapeutic tacrolimus levels. The diagnosis was considered likely to be gadolinium-induced acute pancreatitis following the recent MRI for her optic nerve atrophy. Gadolinium induced acute pancreatitis must be rare. How often does it occur and are there any individuals who are at an increased risk of this?
CHIANG LEE: Yeah, for this case given the temporal relationship between gadolinium administration and the onset of pancreatitis, this was deemed most likely to be the cause. And the absence of any significant graft dysfunction, the absence of hyperglycaemia, or even a detectable C peptide level suggests the pancreas graft is still functioning. And she had a therapeutic tachrolymus level as well on admission, and that that make rejection less likely. Gadolinium-induced acute pancreatitis itself is quite rare and so far there has only been five case reports of gadolinium pancreatitis in native pancreas, and ours was the first reported in a pancreas graft.
Because it's so rare, obviously it's unclear as to which patients are at risk, but what is known is that patients who have repeated exposure to gadolinium-based contrast agent, they have increased retention of gadolinium. And of course, the patient who has got underlying renal dysfunction, they are at risk. But nowadays with the availability of the newer gadolinium-based contrast agents and also different categories of contrast agent predominately macrocyclic components, this leads to less occurrence of any sort of gadolinium-related side effects.
STEPHEN BACCHI: Thank you. Now I’m a neurology registrar talking to a nephrologist about gadolinium adverse effects. So, I have to ask, for our listeners, could you please outline the current thoughts and suggest which guidelines would be good to read about patients with renal dysfunction in the context of nephrogenic systemic fibrosis that may be associated with gadolinium?
CHIANG LEE: Yeah, that's a good one. So, gadolinium-induced nephrogenic systemic fibrosis obviously is widely known to be quite a nasty complication from gadolinium-based contrast agents. Hence, nowadays clinicians are wary of this and the generally accepted practises avoidance of gadolinium-based contrast agents in patients with advanced kidney disease, mainly CKD 4-5 with an EGFR of less than 30 mL per minute or dialysis patients. But despite so, it is very low risk with less than one percent occurrence of nephrogenic systemic fibrosis. There are various clinical guidelines that has been published, for example the Canadian Association of Radiologists, where they have suggested that gadolinium can be considered if there's no imaging modality and, obviously, it is absolutely necessary. And this is only with utilisation of the newer agent such as the macrocyclic compounds, which obviously comes to its risk as well. But the general thought from practise from our end is to try to avoid if at all possible with advanced CKD, EGFR, less than 30 mils per minute.
AMIT SINGH: Thank you. And to wrap up the case for listeners, could you outline the key learning points, take home messages that you took home from this case.
CHIANG LEE: Yeah, so I've got two. In patients with pancreatic graft and abdominal pain, always consider graft pancreatitis. And the differential diagnosis for graft Pancreatitis is white. Always consider viral infections such as cytomegalovirus or CMV infection, which is an opportunistic infection; mechanical complication. It is very important to measure the enzyme levels such as lipase amylase, and also to assess the angiogenesis function by checking the blood sugar level the C peptide level.
The second learning point is although gadolinium-induced acute pancreatitis is rare, it obviously should be considered as a differential diagnosis. But this is a diagnosis of exclusion provided other common causes of pancreatitis have been entertained and excluded.
STEPHEN BACCHI: That does wrap up our recording, but do you mind taking two questions of Amit’s without notice?
CHIANG LEE: Yeah, yeah, sure, sure.
AMIT SINGH: Thank you. So, I guess my first question is with regards to monitoring the severity of disease. With a native pancreatitis, we tend to use the Glasgow-Imrie score or the APACHE score. So I just have a question in regards to if it was a transplanted pancreas, would we still apply this kind of scoring criteria to the pancreas?
CHIANG LEE: Yeah, good question. Look first the diagnosis of acute pancreatitis is based on the Atlanta criteria, which includes, basically, a supportive history of abdominal pain, presence of elevated lipase or amylase level, as well as radiographic finding. Any two out of three criteria supports a diagnosis of acute pancreatitis. In terms of the severity score, yes, there are a few, the one that we've used was the Glasgow-Imrie score which has a higher specificity in comparison to the other scores to diagnose. And for patients with graft pancreatitis. It's the same score that we use.
AMIT SINGH: Yeah. Thank you. My second question is to the graft itself like a pancreas graft. So we give the patient a pancreas graph, we're utilising, we need the endocrine functions off the graph. My question is predominantly, what actually happens to the exocrine function of the graph when we transplant it into someone, does it have an outlet to go somewhere or what happens to you?
CHIANG LEE: Yeah, so, I've got a disclaimer. So, I'm not a I'm not a transplant surgeon or you know a specialist in pancreas grafts. But historically what has happened is the outlet for the pancreatic duct is anastamosed to the bladder, where the exocrine drainage occurs. So, there used to be previously measurements of urinary lipase or amylase level to detect and, you know, that has been done. There have been some complications previously and the other method that has been used to anastamose or to connect this into the small intestine or into the intestine. So yes, so there is a place where the exocrine secretions of the pancreas gets channelled to yes.
STEPHEN BACCHI: Well, thank you again, Doctor Lee. I've certainly learned a lot from this case and I hope I listen as well as well. If they'd like further details they can read the full article, which is titled Titled: “Gadolinium-Induced Acute Graft Pancreatitis in a Simultaneous Pancreas-Kidney Transplant Recipient.” This was published in Case Reports in Nephrology in 2022. The authors, Dr Chiang Lee, Rachel Tan, and Nitesh Rao.
MIC CAVAZZINI: And thanks to Stephen Bacchi and Amit Singh for contributing to this case report for Pomegranate Health. I’d love to hear more ideas for cases and research articles to dissect, or any other issues of importance to Trainees and Fellows alike. Just send an email to podcast@racp.edu.au.
Hopefully you already know about all the other online learning resources provided for members of the RACP. Recent eLearning releases include courses on clinical ethics and culturally safe supervision. And as always, the College Learning Series, or CLS, publishes video lectures every month tied to the Adult Medicine and Paediatric Basic Training curricula.
Subscribe to our podcasts by looking up Pomegranate Health in your favourite pod browser, or you can also sign up to an email alerts list from our home page. This podcast was produced on the lands of the Gadigal clan of the Eora nation. The RACP has a commitment to advancing the health and education of Aboriginal, Torres Strait Islander and Māori people. I’m Mic Cavazzini. Thanks for listening.