Name:
A 33-Year-Old Woman with Recently-Treated Acute Myeloid Leukemia
Description:
A 33-Year-Old Woman with Recently-Treated Acute Myeloid Leukemia
Thumbnail URL:
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Duration:
T00H05M58S
Embed URL:
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Content URL:
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Upload Date:
2022-02-28T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
[upbeat intro music]
DR. HANDY: Hi, welcome to Harrison's Podclass, where we discuss important concepts in internal medicine. I'm Cathy Handy.
DR. WIENER: And I'm Charlie Wiener, and we're coming to you from the Johns Hopkins School of Medicine. Hi Cathy, today's patient is a 33-year-old woman with recently treated acute myeloid leukemia now in remission, who is admitted to the hospital with lethargy, fever, and tachycardia. She is placed on empiric antibiotics, and her blood cultures grow Pseudomonas that is resistant to cefepime within 24 hours.
DR. HANDY: Well, I'm curious why she developed Pseudomonas bacteremia. She supposedly is in remission, so she should have normal white blood cell counts, but I'm worried that she's neutropenic as that's a major risk factor for Pseudomonas bacteremia. If we assume she's not getting active chemotherapy, then this could be a presentation of relapsed AML. Tell me more about the history and what's going on.
DR. WIENER: Okay, well, the question is going to leave the oncologic aspects for now. Because of the resistant organism, she's started on a regimen that includes intravenous gentamicin. Five days after starting gentamicin, her serum creatinine has risen from her baseline of 1.0 mg/dL to 2.4 mg/dL.
DR. HANDY: Okay, so we're talking about acute kidney injury here, and it seems like that's one of the other complicating factors that's going on. What does her urinalysis show? And I'd also want an ultrasound to rule out obstruction.
DR. WIENER: Her urine has slight elevation of protein but has no white blood cells, red blood cells, and no white blood cell or red blood cell casts. A renal ultrasound is unremarkable and shows no hydronephrosis or any evidence of an obstruction.
DR. HANDY: So the renal ultrasound rules out an obstructive cause of her acute kidney injury, and the lack of casts on the urinalysis suggests that there has not been glomerular injury. What's the question asking?
DR. WIENER: So the question asks, which of the following is the most likely mechanism of her acute kidney injury? And the options are A. acute interstitial nephritis; B. acute tubular necrosis; C. glomerulonephritis; D. ischemic injury; or E. obstruction.
DR. HANDY: So I already mentioned that E. obstruction, and C. glomerulonephritis are ruled out because of the tests that you already mentioned and that we went over. Next, we need to think about the cause, and then the mechanism that would be associated with that cause.
DR. WIENER: Given her history, what do you think is the most likely cause?
DR. HANDY: Well, sepsis certainly could be contributing, but you have not told me about any hypotension, any need for vasopressors or shock over the past five days, only worsening renal function. So I'm thinking that this is not primarily related to her bacteremia, but is really more consistent with a drug toxicity. Gentamicin sticks out, and the timing of the acute kidney injury after starting certainly fits with this being the cause of her acute renal failure.
DR. HANDY: Aminoglycosides, which are the class of antibiotics that includes gentamicin and also tobramycin and amikacin, are commonly associated with acute kidney injury. The mechanism of that, though, is through tubular necrosis.
DR. WIENER: Okay, so just to answer the question, the mechanism here is likely B. acute tubular necrosis as the cause of her AKI, right?
DR. HANDY: Correct, acute kidney injury due to aminoglycosides typically manifests after five to seven days of therapy and it can present even after the drug has been discontinued. Nonoliguric acute kidney injury, so a urine volume that's still over 400 mLs per day, accompanies 10 to 30% of courses of aminoglycoside antibiotics even when plasma levels are in the therapeutic range. Aminoglycosides are freely filtered across the glomerulus and then accumulate within the renal cortex, and that's where the concentrations can greatly exceed those of the plasma.
DR. WIENER: In addition to an elevated creatinine, would you expect any other lab abnormalities?
DR. HANDY: A variety of electrolyte abnormalities can be seen in acute kidney injury, including hyponatremia, hyperkalemia, metabolic acidosis, hyperphosphatemia and hypocalcemia. However, specifically associated with aminoglycoside-induced acute kidney injury, hypomagnesemia is a common finding.
DR. WIENER: What about the other causes of AKI listed, specifically, acute interstitial nephritis? That can be due to drugs, right?
DR. HANDY: Yes, acute kidney injury secondary to acute interstitial nephritis can occur as a consequence of exposure to many different antibiotics. So some examples of this would include penicillins, cephalosporins, the quinolones, sulfonamides, and rifampin. She wasn't started on these based on the sensitivities given to the Pseudomonas. There's no reason to think she has ischemic injury by history. Interestingly, ischemic acute kidney injury also mostly manifest by injury to the tubules.
DR. WIENER: So in this case, what would you do next?
DR. HANDY: Well, the main thing you need to do is stop the offending agent and hopefully switch to a different antibiotic, because you do still have to treat her Pseudomonas bacteremia. Mortality rates of untreated Pseudomonas infection are very high, so I wouldn't recommend just stopping antibiotics entirely. Meropenem and piperacillin/tazobactam are two other commonly used antibiotics that have activity against Pseudomonas, so hopefully there is sensitivity to one of those antibiotics.
DR. WIENER: Okay, so the teaching point is that aminoglycosides are commonly associated with AKI, or acute kidney injury that typically occurs five to seven days after starting the medication, and is the result of acute tubular injury. Interestingly, when I was growing up, aminoglycosides were used very, very commonly in oncology patients, and in fact, in bacteremia patients in general.
DR. WIENER: I think with newer agents coming out, I think that many people are less familiar with the use of aminoglycosides in general, so I think this is an important point to remember.
DR. HANDY: And to learn more, you can go to Harrison's chapter on acute kidney injury. [outro music] [Mr. Shanahan] This is Jim Shanahan, publisher at McGraw Hill. Harrison's Podclass is brought to you by McGraw Hill's Access Medicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. Go to accessmedicine.com to learn more.