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Assessment of kidney function in cirrhosis: Are we moving closer to accurate estimation of glomerular filtration rate?

A. Ma,A. Juanola,E. Solà

Published 2022 in Liver international (Print)

ABSTRACT

Patients with liver cirrhosis commonly develop impaired kidney function both in the acute and chronic settings, with associated poor kidney and patient outcomes.1,2 In addition, preexisting impaired kidney function also affects postliver transplant outcomes.3 Thus, most organ allocation policies are based on the model for endstage liver disease (MELD) or MELDSodium (MELDNa) scores, which weigh serum creatinine heavily to account for the importance of renal function. However, the limitations of serum creatinine in the context of cirrhosis are widely known. Whilst general factors such as age, sex and ethnicity influence creatinine levels, there are cirrhosisspecific conditions, including sarcopenia, elevated bilirubin and ascites, that have unpredictable effects on creatinine levels, leading to possible underor overdiagnosis of renal impairment, inequities in organ allocation and even inadequate indication for simultaneous liverkidney (SLK) transplant.4– 6 The increasing prevalence of metabolic syndrome and nonalcoholic fatty liver diseaserelated cirrhosis is expected to lead to increased frequencies of chronic kidney disease (CKD) in cirrhosis, making the assessment of kidney function an even more relevant problem in this setting. Whilst direct measurement of glomerular filtration rate (mGFR) remains the gold standard for the assessment of kidney function,7 it is impractical, expensive and is not always available. Accurate renal function assessment remains an enormous issue in the management of patients with cirrhosis, affecting clinical decisionmaking. In this issue of Liver International, Campion and colleagues present a muchneeded, detailed and comprehensive review that brings clarity as to available tools to estimate GFR in patients with cirrhosis, highlighting major advantages and flaws for each available method.8 Whilst serum creatinine remains an imperfect tool to estimate kidney function in both acute and chronic kidney disease, it is standardized, cheap and widely available. In fact, the very definitions we use for acute kidney injury (AKI) in cirrhosis, hepatorenal syndrome and acuteonchronic liver failure are based on serum creatinine values, and all have excellent correlation with shortand longterm prognosis.1,9,10 Creatinine is clearly here to stay. The true issue is that we need convincing evidence that changing the way renal function is currently estimated will change management and/or patient outcomes, which is no easy feat. The answer lies perhaps in understanding the interplay between renal function and two specific settings: MELDbased organ allocation and SLK transplant. Whilst accurate assessment of kidney function and their implications in patient prognosis is always important, they are crucial in the setting of liver transplantation. In their review, the authors summarized the existing data on the effect of renal function on organ allocation. Sex disparities are a major issue, with women more likely to die or become too sick for transplant whilst on the waitlist.11 The use of serum creatinine in MELDbased systems is likely, at least in part, to blame. It would seem logical that using more novel, less sexinfluenced, biomarkers such as cystatin C (CysC) would decrease such sex inequalities. In fact, there is growing evidence in the setting of cirrhosis that CysC has a better correlation with mGFR than serum creatinine and correlates with prognosis.12,13 The single study of 429 patients from Finkenstedt and colleagues mentioned in this review showed that, although MELDCysC based allocation would lead to less sex differences, it would ultimately not improve the predictive power of MELD for 90day mortality.14 Nevertheless, this was a singlecentre study in which, at baseline, men and women did not have significantly different mortality rates. Thus, these findings cannot be externally applied in settings in which sex outcome disparities do exist. The other proposed novel allocation system that was appraised in this review is the MELDGRAILNa equation, in which creatinine is replaced by eGFR calculated using the GRAIL score (including age, sex, race, creatinine, blood urea nitrogen and albumin).15 With potentially better predictive performance and decreased sex inequities compared to MELD, the authors rightfully point out that this tool is one of the most promising. We can only hope for more prospective studies supporting its use. Very recently, MELD 3.0 has been reported as an optimized version of the MELD score to improve organ allocation. Amongst other adjustments, MELD 3.0 includes for the first time a coefficient to account for the female sex. Results show that this new version of the MELD score is more accurate to predict shortterm mortality than MELDNa and addresses important known limitations of the system, including the disadvantages that women had been facing. Thus, this represents an important step forward in addressing sex disparities in organ allocation.16 Furthermore, most centres consider SLK transplants when the estimated and/or measured GFR falls below 30– 35 ml/min. Overall, CysCbased equations have shown promising results and seem to outperform creatininebased equations. However, they still have

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