Acute kidney injury (AKI) and hyponatremia are common, difficult to prevent, and detrimental to survival of hospitalized patients with severe liver disease, Josh Levitsky, MD, told the attendees of the virtual American Society for the Study of Liver Diseases (AASLD) Annual Meeting on November 13, 2020.

“Patients with cirrhosis admitted to the hospital with AKI have significant diminishment in survival,” he stated.

Dr Levitsky is a professor of medicine, medical education, and surgery at the Northwestern  University Feinberg School of Medicine in Chicago, Illinois.

In patients with cirrhosis, Dr Levitsky said, serum creatinine “is not a good measure, independently, of renal function. Serum creatinine only gives you a value. You really have to correlate that value with glomerular filtration rate (GFR) as well as the patient’s age and comorbidities.”

In cirrhosis, he explained, elevated bilirubin can interfere with serum creatinine assays, and creatinine levels are also more significant when muscle mass is low. Further, Dr Levitsky said, because the cirrhotic liver is not functioning well, production of creatinine is decreased. “This really drives down the serum creatinine in patients with cirrhosis and leads to overestimating GFR.”

It’s important to evaluate renal function at all different stages in cirrhosis, he said, because “large changes in GFR can occur with even just a little change in creatinine. A change from 0.5 to 0.9 in creatinine is a significant change, compared to creatinine going from 3 to 6,” in a patient with cirrhosis. “This is a concept that not everybody is familiar with, and we get less concerned about changes in creatinine at the lower levels when we really should be more concerned because it results in a significant difference in GFR.”

Estimated GFR is “really how it’s done in the clinic,” Dr Levitsky said. Using serum creatinine levels in an equation “with other factors it can provide pretty accurate estimate of GFR, particularly if you use cystatin C, which combined with creatinine gives a more accurate estimate.” Measuring GFR is the most accurate method but it is more expensive and can be difficult logistically, he noted.

The spectrum of AKI in cirrhosis involves a significant amount of overlap between functional renal failure and intrinsic renal failure due to structural renal disease or obstruction. “It can sometimes be difficult to distinguish these etiologies,” Dr Levitsky said. He observed that approximately 20% of hospitalized patients with cirrhosis also have AKI. Of those patients, 68% are prerenal in nature, “and two-thirds of these patients will be volume-responsive and get better with hydration.” Only about one-third of hospitalized patients with cirrhosis and AKI can be classified with type 1 or type 2 hepatorenal syndrome (HRS). These patients do not improve with hydration.

Dr Levitsky noted that the International Club of Ascites has developed new criteria that better define AKI in patients with cirrhosis according to stages 1, 2 and 3. With each stage, increases in serum creatinine from the baseline rise and kidney dysfunction worsens, as does the rate of in-hospital mortality.

The first step in evaluating and managing AKI in patients with cirrhosis is to “look at the patient’s volume status and give them back volume, usually by intravenous albumin, and discontinue their diuretics.” Noting that one-third of patients have some intrinsic acute renal dysfunction, abdominal ultrasound can be used to look for obstruction, which he noted is uncommon but worthy of assessment. “Doing urinalysis and microscopy to look for casts is important, to rule out interstitial nephritis” and other organic causes of renal damage, and an infection workup is mandatory.

For patients who are nonresponsive to fluid repletion, the diagnosis is almost certainly HRS type 1 or 2. Type 1, the most severe, is characterized by the rapid diminishment of GFR and change in serum creatinine. Dr Levitsky noted that the criteria for type 1 are difficult to adhere to. “Diuretics often have a long half-life and need to ‘wash out’ before diagnosis. There may be ongoing fluid loss. The patient may have been given saline rather than albumin, and to really make the diagnosis, you need recent serum creatinine levels.”

“Hyponatremia is also very important. These patients often present with hyponatremia along with HRS,” Dr Levitsky said. “Assessment of volume status is critical. The vast majority of these patients follow the pathway of hypovolemic hyponatremia, with low urine sodium.” Hyponatremia is an independent risk factor for mortality among patients with liver failure. “It is very important to recognize this mortality risk in patients with hyponatremia.”

If hyponatremia is mild there is no need to correct it quickly, he said. If it’s acutely symptomatic, rapid correction and fluid replacement are required. For those who have chronic symptomatic hyponatremia, more conservative treatment in fluid replacement is necessary.

The mortality of hospitalized patients with cirrhosis and AKI makes preventive measures all the more important, Dr Levitsky said. Proven measures that help to prevent AKI in patients with cirrhosis include antibiotic prophylaxis in the case of variceal bleeding; repleting volume with albumin following LVP (over 5 L); close monitoring of electrolytes, urine output, and weight loss when patients are on diuretic therapy; titrating dosage of lactulose to prevent volume loss due to diarrhea; and in cases of spontaneous bacterial peritonitis, providing albumin at day 1 and day 3.

Preventing AKI also requires avoiding aminoglycosides, which he explained is “the absolutely wrong thing to give these patients,” along with intravenous contrasts and nonsteroidal anti-inflammatory drugs.

In some cases of refractory ascites, a transjugular intrahepatic portosystemic shunt may reduce portal hypertension and its complications, especially variceal bleeding, Dr Levitsky added.

“We need more specific and early predictors, such as biomarkers to risk-stratify patients to determine their risk for severe AKI, and to predict their response to therapy,” he said. Such biomarkers can also help to predict which patients may be at heightened risk of AKI following liver transplant, and importantly, which patients are most likely to have reversible AKI, and therefore be less likely to require a simultaneous liver-kidney transplant.

—Rebecca Mashaw

Reference:

Levitsky J. Management of acute kidney injury in the hospitalized patient with cirrhosis. Talk presented at: American Association for the Study of Liver Diseases annual meeting. November 14, 2020. Virtual.