How to approach acute kidney injury in patients with cirrhosis
Does your sympathetic nervous system get activated when you notice acute kidney injury in patients with cirrhosis? Ever wonder how to really diagnose hepatorenal syndrome (HRS)? Think you have the bile-acid-stones to start diuretics on a patient requiring pressor support for kidney failure? You have come to the right place! Listen to @kidney_boy Joel Topf, HRS expert Juan Carlos Velez (@veleznephhepato), and self-proclaimed most-handsome-nephrologist Bill Whittier (@TWhittier_RUSH) tackle the complex pathophysiology and treatment of hepatorenal syndrome in this NephMadness 2019 special episode!
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Written and produced by: Justin Berk MD, Nora Taranto MS4
Hepatorenal syndrome (HRS) low perfusion of kidney from persistent liver disease
Pre-renal low perfusion of kidney from low volume, would improve once euvolemic
Acute tubular necrosis (ATN) low perfusion such that kidney in shock physiology, treatment is supportive while still trying to establish euvolemia
Parenchymal disease from inflammatory conditions like autoimmune or hepatitis-induced glomerular disease, consider the cause of cirrhosis
Medications can also cause AKI and should be reviewed (e.g. spironolactone, TMP-SMX)
Determine Volume Status
Dr. Velez: “You cannot underestimate a good history and physical.”
History related clues: weight changes, excessive diarrhea from lactulose, recent medication changes
Physical Exam findings: ascites (soft vs tense as compared to baseline), leg edema (most patients with ascites have leg edema, and lack of edema suggests low volume), signs of pleural effusions
Urinalysis can help distinguish between parenchymal kidney damage and decreased perfusion.
In pre-renal AKI, the urinalysis should be “bland” (without protein, blood, or casts) though may have hyaline casts
Beware: patients with cirrhosis and elevated bilirubin may have stained hyaline casts (discolored from bilirubin) that are misinterpreted as muddy brown granular casts seen in ATN
Dr. Topf expert opinion: Usually, there is going to be something [on UA] so this is not always helpful in ruling out other causes
Urine eosinophils are not a high yield test in practice (BUT, they’re helpful on the boards to diagnose acute interstitial nephritis).
Urine sodium or fractional excretion of sodium can also help distinguish etiology.
Low urine sodium may suggest hepatorenal or prerenal, but does not rule other causes because in cirrhosis the urine sodium is generally low.
High urine sodium may suggest ATN.
While our TWDFNR episode advised against urine electrolytes in most AKI, you may remember investigating hepatorenal syndrome was an exception.
Renal ultrasound can evaluate for post-renal obstruction. Though lower yield and unclear if cost-effective, our nephrologists all agree that it is low-risk, inexpensive, and they use it to rule out easily reversible causes of AKI. Post-void residuals using a bladder scanner, while useful to rule out obstruction in other patients, are often difficult to obtain in patients with cirrhosis. Dr Whittier notes foley catheter can be considered (diagnostic and therapeutic for obstruction).
“It’s a test with no risk to the patients and rare cause of AKI that is immediately fixable… Treatment of obstruction should not be dialysis.”
Joel Topf gives us his expert opinion on why it’s unacceptable to miss acute urinary obstruction as a cause of AKI.
Circulatory Dysfunction in Hepatorenal Syndrome
Advanced cirrhosis can lead to circulatory dysfunction, specifically splanchnic vasodilation causing blood to pool in the mesenteric circulation and low effective circulatory volume. This leads to increased sympathetic and renin-angiotensin-aldosterone system (RAAS) activation in an attempt to increase systemic blood pressure. In decompensated cirrhosis, the RAAS activation is enough to constrict renal arterioles & decrease kidney perfusion. BUT, this activation cannot successfully increase mean arterial pressure (MAP).
Clinical clue: If SBP > 140, hepatorenal syndrome becomes less likely
Two mechanisms contribute to decreased renal perfusion
A “stiff” liver leads to the release of nitric oxide and other splanchnic vasodilators. This leads to poor effective circulatory volume and RAAS activation.
The hepatorenal reflex hypothesis suggests increases in portal pressure also send a sympathetic signal to the brain itself to activate the RAAS system.
Both activations of the renin angiotensin system lead to the release of vasoconstrictors (norepinephrine and angiotensin), which ultimately decreases blood flow to kidneys.
Next Steps in AKI in Cirrhosis
Volume status is very difficult to assess. Trial resuscitation or diuresis and monitor response.
Dr. Whittier expert opinion:Don’t treat with both diuretics and volume resuscitation at the same time when you are unsure of volume. Pick one clinically: Do you think volume up or volume down? Select based on best clinical judgement and what’s likely to cause the least harm. Give enough to make sure you know if it worked or not.
Colloid fluid resuscitation if “volume down”
Fluid resuscitation trials help determine if the cause of AKI is pre-renal. AKI should improve with euvolemia. Most patients with cirrhosis have ascites and peripheral edema. Lack of edema may suggest hypovolemia.
In patients with cirrhosis, colloid resuscitation is preferred over crystalloid.
This is dogma and based on expert opinion, given colloids can theoretically maintain osmotic pressure intravascularly and not worsen ascites.
Dr. Topf expert opinion: The volume of distribution of normal saline will go to ascites very quickly and is not effective.
JCV expert opinion: It is not unreasonable to use normal saline if the patient is “volume down” from overdiuresis or increased diarrhea.
Please recall that our chief of hepatology, Scott Matherly, recommends using crystalloids for fluid resuscitation in a cirrhotic patient with variceal hemorrhage and hypotension (in addition to blood products) or sepsis to maintain pressure –episode 142 Cirrhosis TIPS.
Diuresis or paracentesis if “volume overload”
Often patients with cirrhosis have water and volume overload and can benefit from diuresis.
Furosemide is typical diuretic to help remove fluid. Dr. Topf expert dosing equation: 20 multiplied by the creatinine.
Kashlak Pearl: Decreased muscle mass and decreased creatinine production from liver disease cause relatively low creatinine and GFR is often overestimated. Therefore, a higher dose may be needed.
Spironolactone(an aldosterone antagonist) can be helpful to combat the effects of the RAAS activation.
Spironolactone can cause hyperkalemia so potassium must be closely monitored.
While a 5:2 ratio of spironolactone:furosemide is dogma for refractory ascites, the spironolactone can be dangerous if the kidneys are failing. Inadequate urine output impairs potassium excretion.
Large volume paracentesis (LVP)
LVP is indicated if lots of fluid needs to be removed. The goal is euvolemia.
Dr Whittier expert opinion:We try to gradually remove urine (e.g. CCVHD rather than intermittent hemodialysis) and so I’d rather have 2L every other day than 7L once a week. It’s based on gestalt.
Dr. Topf expert opinion:I like the large volume to get the fluid off. I start albumin early. I worry about tense ascites collapsing the renal vein or IVC and putting back pressure on the kidneys.
JCV expert opinion:It’s difficult. LVP is common trigger for HRS but abdominal compartment syndrome is also dangerous. If evidence of abdominal compartment syndrome, I usually do LVP but acknowledge it can worsen kidney function. In many HRS trials, LVP is “allowed” suggesting it is deemed appropriate.
JCV’s Expert opinion:If on pressor support, renal perfusion can be guaranteed so it’s OK to do LVP. (Maybe even resume diuretics?)
Diagnosis of HRS
Hepatorenal syndrome should be considered in patients with cirrhosis and ascites who present with an acute kidney injury not explained by other causes. It does not respond after a trial of volume expansion.
No macroscopic signs of kidney injury (i.e. no significant proteinuria, microhematuria, or renal US findings)
JCV expert opinion: an “albumin challenge” is 25g IV Q6 hours for the first 24 hours
Improvement of AKI with volume expansion suggests a pre-renal injury
Any change in clinical status may be a trigger for HRS (peritonitis, UTI, encephalopathy, LVP).
Dr Topf expert opinion: What is prognosis of the patient who has Type 1 HRS that you do not reverse? …If they don’t get a liver transplant quickly, within a couple of weeks, they are probably going to be dead.
Sometimes hemodialysis can prolong life enough to become a liver transplant candidate, for example those with alcoholic cirrhosis completing an alcohol abstinence period.
Goals and Learning Objectives
Listeners will develop a general understanding of hepatorenal syndrome and understand the diagnosis, pathophysiology, and treatment modalities for this condition.
After listening to this episode listeners will…
Define common terms: hepatorenal syndrome (type 1 and type 2),
Identify the potential causes of elevated creatinine in a patient with cirrhosis
Identify the steps needed to diagnose hepatorenal syndrome
Describe the pathophysiology of hepatorenal syndrome
List the treatment modalities for HRS
Differentiate terlipressin and octreotide/midodrine
Dr. Velez, and Dr. Whittier report no relevant financial disclosures.Dr Topf lists the following disclosures on his website “I have an ownership stake in a few Davita run dialysis clinics and a vascular access center. Takeda Oncology made a donation to MM4MM the program that is taking me to Mount Everest in 2018”. The Curbsiders report no relevant financial disclosures.