Agbim, U. and S. K. Asrani (2019). “Cirrhosis and the Acute Kidney Injury/Chronic Kidney Disease Continuum: The Path Chosen Matters.” Clin Gastroenterol Hepatol Apr 17. [Epub ahead of print].
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The study [Cullaro G., Verna E.C., and Lai J.C.: Association between renal function pattern and mortality in patients with cirrhosis. Clin Gastroenterol Hepatol 2019] notably raised several important issues. First, renal dysfunction is exceedingly common and the temporal dimension of where the patient lies on the AKI/CKD continuum may matter. Although a mathematical model such as the MELD or MELD-Na may attempt to summarize AKI, CKD, or AKI/CKD by a singular serum creatine concentration or its surrogates, these may be 3 separate entities, each with their own trajectory. A young cirrhotic patient with a MELD score of 25 and a serum creatinine concentration of 2 mg/dL driven by AKI owing to volume depletion may have a different trajectory than an older cirrhotic patient with a similar MELD but volume depletion complicating underlying CKD. Overall, AKI exerts a greater influence in risk of mortality on CKD than it does on those with normal renal function. Intuitively thinking, this makes sense because any insult, whether small or large, on an otherwise diseased kidney can drive cirrhotics in an unfavorable direction. This is relevant given the increasing prevalence of CKD in this population, necessitating favorable strategies to avoid or mitigate further renal injury, thereby minimizing the potential for waitlist mortality. Hence, mechanisms and chronicity of renal dysfunction may be important even before an eventual transplant. Second, this study emphasized the need to measure renal function effectively. 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. Several biomarkers, in addition to patient characteristics, currently are being evaluated to assess renal function. The operationalization of AKI, particularly in cirrhosis, has been problematic throughout the literature, and it will be necessary to formalize a consistent definition to measure the real effect of renal dysfunction. Furthermore, AKI represents a heterogeneous entity with a multitude of phenotypes (hypovolemic nephropathy, vasogenic nephropathy, acute tubular necrosis, hepatorenal syndrome), as does CKD, and it is unclear in this analysis how any particular AKI phenotypic insult influences risk. Finally, the study highlighted the importance of extrahepatic factors in determining mortality on the waitlist. Although in all comers, a mathematical model such as the MELD-Na score may be able to predict that a registrant with a higher MELD-Na score has an increased risk of mortality than someone with a lower MELD-Na score (e.g., score of 40 vs 6), the ability of any statistical model to parse out differences in patients with similar MELD scores is difficult. The presence of comorbid conditions, malnutrition and sarcopenia, infections, critical illness, and now pattern of renal dysfunction, all may play a role. (Excerpt from text of editorial, article in press, not paginated.)
