Acute kidney injury (AKI) alone, or in combination with chronic kidney disease (CK), significantly increases mortality risk in cirrhotic patients waiting for a liver transplant. A study published in Clinical Gastroenterology and Hepatology underscores the importance of assessing renal function patterns to improve risk profiles in these patients, setting the stage to investigate more efficient biomarkers on kidney injury.
Half of all patients with cirrhosis that develop renal failure die within 30 days. “However, renal dysfunction in the context of cirrhosis arises from a broad spectrum of pathologies,” including AKI or CKD. Whether these two conditions affect survival equally, is not well known, wrote the investigators.
The researchers sought answers in a 90-day retrospective study of more than 22,000 adult patients on the liver transplant list with the United Network for Organ Sharing/Organ Procurement and Transplantation Network. On average, these patients had spent approximately 1.6 years on the transplantation list and about 5 years participating in renal function assessments.
The investigators assigned patients to four groups based on the following renal function patterns:
- AKI: an increase in serum creatinine by ≥0.3 mg/dL or ≥50% in the last 7 days or <72 days of hemodialysis;
- CKD: estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 for 90 days with final eGFR of ≤30 mL/min/1.73 m2 or ≥72 days of hemodialysis;
- AKI on CKD: meeting both AKI and CKD definitions; and
- 7 Normal renal function: meeting neither definition.
Patients’ serum creatinine and eGFR had been tracked serially while they were on the time the transplant list. The researchers used the Chronic Kidney Disease Epidemiology Collaboration creatinine-based (CKD-EPIcr) equation to calculate eGFR. This formula was chosen because “some cirrhosis literature shows that it most closely approximates GFR in patients with liver disease,” lead study author Giuseppe Cullaro, MD, MAS, a transplant hepatology fellow at New York Presbyterian Hospital, told CLN Stat.
To establish any associations between transplant waitlist mortality and renal dysfunction, the investigators performed competing risk analyses, adjusting for confounders using the model for end-stage liver disease sodium (MELD-Na) scores. Among 22,680 patients on the waitlist, 13% and 31% had episodes of AKI and CKD, respectively. About 29% either died or were too sick to remain on the list.
Survival rates varied among the four renal function patterns. “We demonstrated that those with an acute worsening of their renal function (ie, AKI or AKI on CKD) were at significantly higher risk of waitlist mortality than both those with stable CKD and those with normal renal function, even after controlling for final MELD-Na score,” the investigators summarized.
“We hypothesize that the mechanism by which renal function patterns have a varying impact on survival in patients with decompensated cirrhosis is related to the etiology of the renal dysfunction,” they continued. Patients with AKI or a combination of AKI with CKD, for example, may have experienced infection, bleeding, or some other type of event that could have increased their mortality risk.
“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 researchers concluded. Next steps are to focus on incorporating renal function patterns into the MELD-Na score to optimize its accuracy.
The importance of measuring renal function effectively is an important takeaway of this study, Uchenna Agbim, MD and Sumeet Asrani, MD, wrote in a related editorial. “All serum creatinine-based equations overestimate GFR in the presence of renal dysfunction. Furthermore, several equations assume a stable GFR, which is not often the case in cirrhotic patients on the waiting list. Risk stratification remains paramount, requiring continual enhancement of tools,” wrote Agbim and Asrani.
Cullaro agreed that all calculations of GFR assume static renal function, which is not often the case. “In fact, in the kidney literature there is a description of kinetic GFR which incorporates rates of change that may be warranted to investigate in patients with end-stage liver disease.”
Future research should focus on more effective use of existing biomarkers and identifying better AKI biomarkers to assess risk and patients’ renal status, suggested the editorialists. “There may be differential effects on morbidity and mortality in cirrhotic patients,” they wrote. “More importantly, this will drive the development of concerted efforts focused on minimizing risk for renal injury and incorporate relevant biomarkers into refined predictive models that guide clinical management and allocation guidelines to truly identify patients at highest risk.”