Acute Kidney Injury: Trends, Trouble, and Time

Podcast Transcript

Dr. Andrei Brateanu:

Welcome to the Medicine Grand Rounders podcast, a platform dedicated to exploring key topics in internal medicine, highly relevant to the medical community. This podcast is made possible through the generous support of a grant from the Cleveland Clinic Education Institute. However, the views and opinions expressed here are those of the speakers and do not necessarily reflect the official position of the Cleveland Clinic. Each episode brings together world-class experts and distinguished physicians from Cleveland Clinic to share their knowledge, experience, and perspectives on issues that impact health care professionals and patient care. Our discussions aim to promote learning, advance professional development, and inspire meaningful conversations with the medical community. Today's episode is hosted by Dr. Nitu Kataria, internal medicine physician at the Cleveland Clinic, and me, Dr. Andrei Breteanu, also in internal medicine. We invite you to join us as we delve into today's thought-provoking topic.

Matthew Coulter:

Hi, my name is Matthew Coulter, and I'm a fourth-year medical student at Case Western Reserve University School of Medicine. Today I'm excited to be joined by Dr. Yasin Obidat, a transplant nephrology fellow and incoming staff here at the Cleveland Clinic, to walk us through his approach to AKI, as well as a few cases regarding the diagnosis and management of acute kidney injury. Thank you, Dr. Obidat, for joining us.

Dr. Yasin Obidat:

Thanks for having me. I'm excited to be here.

Matthew Coulter:

Generally, in this podcast, we like to go over hypothetical cases and discuss the speaker's thoughts on the case. Given causes of acute kidney injury are so diverse, perhaps we can start off broadly with your approach to AKI and then discuss cases that may highlight certain points. When you get a consult for AKI, where do you start?

Dr. Yasin Obidat:

Well, I always like to get an idea of urgency and severity first. So what I start with is what most people have: the serum creatinine, and of course, any obvious needs for dialysis. Though I think there are a lot of points to highlight. In nephrology, it's all about trends. Oftentimes we hear things like, oh, patient has a normal creatinine of 1.0. A creatinine of 1.0 can't be generalized. People with liver cirrhosis, elderly ladies, malnourished individuals, people who've been hospitalized for a long time, who have lost their muscle mass, oftentimes have a lower baseline creatinine, even 0.5 or even lower. And in these individuals, AKI or CKD is often missed. So rather than going by definitions of AKI, or rise in creatinine of 0.3 within 48 hours, or staging and such, what matters most is the trend. Are things getting better? Are things getting worse? And how does it compare to their baseline over the past year?

Matthew Coulter:

So when evaluating AKI, do you usually go by serum creatinine or urine output?

Dr. Yasin Obidat:

Well, that depends on the scenario. First, we have to realize there are many limitations to each marker. When it comes to creatinine, we know that creatinine is a breakdown product of creatine, which comes from muscle. We all know then if you have reduced muscle mass, you will have a lower baseline creatinine, and therefore even a small change in creatinine results in a larger change in GFR. So there are situations where you have decreased creatinine production as well — during acute inflammation, sarcopenia where you have muscle loss, which is very common in settings of prolonged illness. Also, serum creatinine could be diluted during volume overload, even iatrogenic. When we give IV volume resuscitation, we can see a change in creatinine not due to improvement in GFR, but because of dilution. Creatinine often lags behind true changes in kidney function. So for example, if you do a bilateral nephrectomy and immediately measure creatinine, it'll be almost unchanged. But you know at this time, the patient effectively has a GFR of zero because they have no kidneys. So it's a measurement of a single time point and doesn't reflect active or dynamic GFR. And then people often like to mention cystatin C. And cystatin C also has its limitations. True, it's beneficial in people who have low muscle mass, but it's more accurate in people who have higher GFRs, though could be affected by many other things. For example, it could be increased by obesity, diabetes, inflammatory states including sepsis, steroid use, smoking, malignancies. When it comes to urine output, of course, in an ideal situation that would be the best marker of kidney function. But realistically, it's only reliable in the ICU and occasionally on the floor. That's because it's difficult to measure. And if you aren't obtaining hourly measurements, even that can technically lag behind. So overall, you can never rely on a single marker. It's best to look at the overall picture.

Matthew Coulter:

Then how do you determine the cause of AKI?

Dr. Yasin Obidat:

Well, we're all familiar with the broad categories of AKI, right? Pre-renal, post-renal, and intra-renal. And then intra-renal is divided into four or five categories. Realistically speaking, though, a resident or a hospitalist isn't going to go through — and they shouldn't have to go through — all of the differentials in every case of AKI. But it is important to go through all three broad categories in every patient. And when considering intra-renal causes and less common causes of AKI, it's always helpful to have a nephrologist on board. I'd say that when you're evaluating a new AKI, there are four things you should look into for every patient: hemodynamic changes, medications, urinary retention, and contrast.

Matthew Coulter:

And can we break those down and discuss them one by one?

Dr. Yasin Obidat:

Absolutely. So let's start with the hemodynamics. When I open a chart, I'm looking during this hospitalization: were there any episodes of obvious hypoperfusion states? For example, was there any frank hypotension, any relative hypotension — say blood pressure going from 180 to 100 — any episodes of severe hypertension, bradycardia, tachyarrhythmias, hypoxemia, sepsis, blood loss? All of these, even when they're brief, can contribute to an AKI and ATN. If there are any procedures, I always find it helpful to go through the anesthesia notes. You can see drops in blood pressure, the need for pressors, boluses. Overall, patients who have ischemia resulting in an AKI typically have a low systemic perfusion, which oftentimes is volume depletion, but their blood pressure may not fall dramatically, but instead appear to be within normal range. And this could be due to two things. One, either there was an unobserved drop in blood pressure, so it wasn't measured at the time, or you have increased renal susceptibility to AKI, even with modest reductions in perfusion. So there's a concept called autoregulation. When there's a decrease in renal perfusion, the kidneys autoregulate by decreasing the glomerular afferent arteriolar resistance, mostly through prostaglandins. And this drop in the afferent resistance sustains glomerular capillary pressure, which is the driving force of filtration. There's also an increase in efferent glomerular arteriolar resistance, which is mostly mediated by angiotensin II, which also maintains glomerular filtration pressure. So when you have a decrease in the ability to autoregulate — for example, if you're on NSAIDs, which block prostaglandins, or ACE inhibitors and ARBs that block the effect of angiotensin II, or you have more chronic conditions, so you have hyalinosis of the vessels from chronic hypertension, atherosclerosis, even just being elderly — these things prevent the ability of the vessels to dilate, and the kidneys become more vulnerable, even to moderate changes in perfusion. For example, a healthy person might maintain normal GFR even with moderate drops in their mean arterial pressure. But when they're on these medications — NSAIDs, ACE inhibitors, ARBs — every drop in blood pressure actually can decrease GFR, which kind of transitions us into the second point, being medications. The reason we recommend to hold NSAIDs, which is often seen in orthopedics or gynecology, and chronic ACE inhibitors or ARBs, isn't necessarily as a cause of AKI, but because of their ability to increase their susceptibility to AKI. Other medications to look for as causes, which are less frequent: bisphosphonates, aminoglycosides, amphotericin. If it were more of a subacute rise, then you can look at recent antibiotic use over the past few weeks or even months. It's always important to make sure that medications are appropriately dosed. Common medications we see are heparin — for example, heparin products like enoxaparin — analgesics, narcotics, gabapentin. Insulin is also renally cleared, and almost all antibiotics, especially cephalosporins, which can cause severe neurotoxicity.

Matthew Coulter:

So we spoke about hemodynamics, autoregulation, medications. How about urinary retention?

Dr. Yasin Obidat:

That's an easy one. Urinary retention is common and extremely easy to rule out. While hospitalized, there are many factors that contribute to urinary retention. You have immobility, medications — analgesics, antipsychotics, benzos — anesthesia, infections. These all can worsen urinary retention, even in those who don't have it at baseline. And anyone who has an AKI deserves at least a bladder scan, because it's so easy to rule out but can have really important implications. In most cases, an ultrasound isn't needed unless for some reason you suspect obstruction at a higher level of the urinary tract.

Matthew Coulter:

So that brings us to contrast nephropathy. Is that real?

Dr. Yasin Obidat:

Absolutely. So regarding arterial contrast, there's no doubt or controversy. Contrast triggers the release of vasoconstrictors and reduces vasodilators, which causes intrarenal vasoconstriction. And it's also directly toxic to tubular cells. When it comes to venous contrast, such as CT scans, there have been many studies that show an association between contrast use and a rise in creatinine. Clinically, you will undoubtedly see many cases of contrast-associated kidney injury. And here maybe the terminology matters, where it's contrast-associated and not necessarily contrast-induced. The reason there's been controversy over recent years is because there's this large European study that came out in 2022 stating there's no significant difference in AKI in over 100,000 patients comparing contrast studies and non-contrast studies. But there are many caveats. This was not a randomized controlled study. It was a propensity-matched study. So they included 21 different observational studies, which differed substantially in their population, their methods, their definition of AKI, and others. And propensity studies don't account for differences in practices — so for example, the volume of contrast, the timing, what their baseline GFR was, volume management, what other medications patients might have been on. And even this study, which raised the controversy, as well as previous studies, showed that maybe not everyone will develop contrast-associated AKI, but there are people who are at higher risk. So for example, people who are in hypoperfused states or low effective circulation, diabetics, elderly, recurrent exposure, arterial contrast. And the most important risk factor really is reduced GFR, whether baseline CKD with a GFR less than 45 or even episodes of AKI. Typically what you'd see with contrast-associated AKI is a transient rise in creatinine. So it typically increases within 48 to 72 hours after contrast and resolves within five to seven days. The key matters here are choosing your patients correctly and optimizing renal perfusion. We should, though, always look for the alternative causes like we spoke about earlier — hemodynamics, obstruction, medications. But at the end of the day, if someone needs contrast, they need contrast. We can deal with the AKI that might or might not develop, but you shouldn't necessarily delay contrast studies out of the fear of AKI — for example, in someone who you're highly suspicious of a PE and CTA will significantly change management.

Matthew Coulter:

Great. Thank you for that overview. How about we go over a couple of cases and discuss your approach?

Dr. Yasin Obidat:

Sounds great.

Matthew Coulter:

A 72-year-old lady with a history of hypertension on lisinopril presents to the hospital with three days of right upper quadrant abdominal pain and fever. She was diagnosed with acute cholecystitis and started on antibiotics with plans for surgery. Her blood pressure has been running borderline low, with systolics in the 100s. As a result of her symptoms, she has had poor oral intake. She has been taking ibuprofen for fever and pain. Her creatinine on admission was 1.5 from a baseline of 1.1, and you are now being consulted with a creatinine of 2.5. What are your thoughts on this, and what workup would you obtain?

Dr. Yasin Obidat:

This patient has many clear reasons to have an AKI. She's borderline hypotensive. She's had poor oral intake, likely causing hypovolemia and reduced renal perfusion. She's on lisinopril and ibuprofen, which limits the autoregulatory mechanisms of the kidney. She has an active infection, which causes cytokine release, which can cause tubular injury. And with all of these simultaneously, I would assume she likely developed ATN and is no longer purely in a pre-renal state. In these obvious cases, it's always best to address the reversible causes, get a standard workup, and consider broader differentials should she not improve. So in this case, I would volume resuscitate based on my volume exam. I would stop her ACE inhibitor, hope she's no longer getting any NSAIDs while inpatient, and treat the infection. As in all patients with AKI, it's always important to go over the four things mentioned earlier: hemodynamics, a good volume exam, medications, possibility of obstruction with a bladder scan or an ultrasound, and look for contrast exposure. All patients with an AKI should at least have a urinalysis. A urinalysis, if bland, can suggest ongoing hypoperfusion as the major cause. If you see casts, which are better seen under microscopy, that can support your diagnosis of ATN. And any significant proteinuria might make you consider other differentials, including glomerulonephritis. In general, if I see that the patients don't have this done before the time of consult, I would order a urinalysis, a urine sodium, urine protein to creatinine ratio, and a urine albumin to creatinine ratio.

Matthew Coulter:

That makes a lot of sense. Let's say this patient's kidney function continues to worsen despite these measures, and the team is now asking about dialysis. What are the indications for dialysis?

Dr. Yasin Obidat:

First, I'd say at this point, I'd much favor an ischemic or a septic ATN in this patient given the course. Any purely pre-renal or post-renal cause of AKI should rapidly reverse with correction of the hypoperfused state and appropriate treatment, if there hasn't already been tubular injury. Should this continue for much longer than expected, then you can consider other things, like infection-related GN in this case. On that note, if this patient likely has an ATN, there's not much to do but supportive management. We're always going to feel inclined to do something — maybe more fluids, more diuretics, change something else. But what most people with ATN need is time. That could be days, it could be weeks. If there are no indications for dialysis, just monitor and support. Many people will be inclined to retrial IV fluids, but that could actually be harmful, because oftentimes these people have low urine output and more volume you're giving them is contributing to volume overload and might push them towards dialysis. Regarding dialysis, honestly we use the same acronym medical students use — AEIOU: acidosis, electrolytes, intoxications, overload, and uremia. Though what I would highlight is all of these indications are for refractory causes, not responding to medical management. For example, if you have a patient who's hyperkalemic, 6.7, you might be nervous, but this patient also has acidosis. They're also hypovolemic, they have mild obstruction, maybe they're on medications like Bactrim. All of these things are reversible, and if you treat them, we'll likely resolve the hyperkalemia and not need dialysis. In most cases, dialysis in the acute setting is for hyperkalemia or refractory volume overload, sometimes acidemia, and really much less common for other causes.

Matthew Coulter:

Thank you for that overview. How about we go over one more case? A 55-year-old male with a history of heart failure with reduced ejection fraction presents to the hospital with two weeks of dyspnea on exertion, lower extremity edema, and a 30-pound weight gain. He was started on IV diuretics, though his creatinine began to rise. His creatinine on admission was 1.1 and is now 1.5, and a urine sodium is less than 20. As a result, the team suspects he is now hypovolemic and discontinues diuretics. His creatinine continues to worsen, and nephrology is consulted for AKI.

Dr. Yasin Obidat:

That's an excellent example, because we face this very frequently. I think it's important first to understand what's happening on the kidney level when it comes to cardiorenal syndrome. Cardiopulmonary perfusion depends on the gradient between the high arterial pressure towards the kidney and the low venous pressure away from the kidney. When you have high preload and you're volume overloaded, you develop venous congestion, and that venous congestion increases the venous pressure, so you have a decrease in the gradient between the arterial pressure and the venous system. Now you have poor effective blood flow, and in severe cases, you can even have reverse blood flow in the kidney if the venous pressures are very high. The only way to manage this is by removing volume, ideally with IV diuretics. A few things we see when it comes to cardiorenal syndrome: first, like in this case, creatinine begins to rise, and diuretics are stopped, thinking the diuretics were the cause. And the only way diuretics will really cause an AKI in the acute setting is volume depletion. If someone's volume overloaded and creatinine is rising, it's not the diuretics — unless they're truly now volume deplete, which is unlikely in this case where they gained 30 pounds. Alternatively, perhaps the rate of volume removal was high and they may have had transient hypotension, but ultimately what you need to do is remove the volume. And what can happen is not truly an AKI, but rather a rise in creatinine, irrespective of GFR. So diuretics promote volume removal, and intravascular volume decreases, which concentrates the plasma, including creatinine. So this is more of a measurement artifact rather than a reduction in GFR. In fact, studies show that patients who achieved successful decongestion with hemoconcentration had a rise in creatinine and improved outcomes. Another common scenario is the creatinine begins to rise, and you truly do believe the patient is volume deplete after multiple days of diuretics because there's no peripheral edema. And here I think the main problem people face is the term peripheral edema. It's not just peripheral, it's dependent — as in, dependent on gravity. So very often I'll see patients labeled as euvolemic or even dry because there's no edema in their ankles. But when I'm examining their thighs or their sacrum, my entire fist is lost. And typically these patients do also have JVD on exam. So it's always important to examine them proximally as well as distally. As in all cases of AKI, again, if you're having a rise in creatinine, look for alternative causes — obstruction, contrast, hemodynamics — especially if they've been in the hospital for a long time. But also look at how well you're truly diuresing them. Just because you're on diuretics, perhaps you're not achieving a goal net balance day to day. Oftentimes patients are actually running net positive each day, and that might be the cause. The last thing I'd like to clarify is the urine sodium. Low perfusion states trigger the body to conserve sodium through the RAAS system — renin, angiotensin, aldosterone system. So when you have a decrease in glomerular capillary pressure and GFR, the renal tubules are reabsorbing sodium, urinary sodium decreases, so you have a low urine sodium, typically less than 20. Oftentimes people interchangeably use hypoperfusion with hypovolemia, and that's not correct. Like we were talking about, even in states of cardiorenal syndrome, you have poor effective renal blood flow, and that will also cause a low urine sodium state. So in this case where someone is symptomatic with dyspnea, they've gained about 30 pounds, and they have a low urinary sodium with a rising creatinine, it's more likely that you're not effectively removing volume rather than having developed hypovolemia or the diuretics causing an AKI.

Matthew Coulter:

That's very insightful. Thank you for that. That brings us to the end of this podcast. Are there any final pearls you'd like to share?

Dr. Yasin Obidat:

So first, always remember the common causes of AKI: hemodynamics, obstruction, contrast, medications. Also, everyone with an AKI deserves a review of all of those, as well as an accurate volume exam. Don't forget the proximal extremities, urine studies, a bladder scan, and don't make judgments on volume status based on serum creatinine. Go by your exam and supportive findings, whether it's a chest x-ray or POCUS. Also, ATN takes time. Don't rush to change management because creatinine isn't improving. Something I was taught during my training was, don't just do something — stand there. And I love that. And one last point the fellows would appreciate: it's always best to consult when the AKI is developing rather than resolving. But honestly, it's better to be involved earlier rather than later, when the patient is on the verge of dialysis.

Matthew Coulter:

Well, thank you so much, Dr. Obidat, for being here and for the incredibly insightful conversation that we've had today. I think we've all really learned a lot.

Dr. Yasin Obidat:

Thanks so much for having me.

Dr. Andrei Brateanu:

To our listeners, thank you for joining us on this deep dive into this important topic. We hope you found this episode both educational and engaging. On behalf of the team, thank you to our special guests who joined us today. Thank you also to the Cleveland Clinic Education Institute for the educational support of this project. Until next time, please enjoy this and future podcasts from the Cleveland Clinic Medicine Grand Rounders.