From the AGA Journals

Type of renal dysfunction affects liver cirrhosis mortality risk

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Cirrhotic patients are also at risk of chronic kidney disease

Cirrhotic patients with renal failure have a sevenfold increase in mortality compared with those without renal failure. Acute kidney injury (AKI) is common in cirrhosis; increasingly, cirrhotic patients awaiting liver transplantation have or are also at risk for CKD. They are sicker, older, and have more comorbidities such as obesity and diabetes. In this study, the cumulative incidence of death on the wait list was much more pronounced for any form of AKI, with those with AKI on CKD having the highest cumulative incidence of wait list mortality compared with those with normal renal function. The study notably raises several important issues. First, AKI exerts a greater influence in risk of mortality on CKD than it does on those with normal renal function. This is relevant given the increasing prevalence of CKD in this population. Second, it emphasizes the need to effectively measure renal function. All serum creatinine-based equations overestimate glomerular filtration rate in the presence of renal dysfunction. Finally, the study highlights the importance of extrahepatic factors in determining mortality on the wait list. While in all comers, a mathematical model such as the MELDNa score may be able to predict mortality, for a specific patient the presence of comorbid conditions, malnutrition and sarcopenia, infections, critical illness, and now pattern of renal dysfunction, may all play a role.

Dr. Sumeet K. Asrani, Baylor University Medical Center, Dallas

Dr. Sumeet K. Asrani

The study raises questions ripe for further study: Should we incorporate pattern of renal injury into prognostic models and allocation? Investigation should focus on identifying and validating biomarkers that represent the many phenotypes/mechanisms of AKI/CKD as there may be differential effects on morbidity and mortality in cirrhotic patients.

Sumeet K. Asrani, MD, MSc, is a hepatologist affiliated with Baylor University Medical Center, Dallas. He has no conflicts of interest.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 for 90 days with a final rate of at least 30 mL/min/1.73 m2. Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

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