GFR Estimating Equations and Liver Disease

Abstract

It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver disease in order to deliver care and allocate organs for transplantation in a way that improves outcomes. The most commonly used methods to estimate GFR in this population are based on creatinine, which is biased by these patients’ low creatinine production and potentially by elevated serum bilirubin and decreased albumin levels. None of the creatinine based estimated GFR (eGFR) equations have been specifically modified for a population with liver disease, and even measurement of a 24 hour creatinine clearance has limitations. In liver disease, all creatinine based estimates of GFR overestimate gold standard measured GFR (mGFR), and the degree of overestimation is highest at lower mGFR values and in more severe liver disease. Cystatin C based eGFR has shown promise in general population studies by demonstrating less bias than creatinine based eGFR and improved association with clinically important outcomes, but results in the liver disease population have been mixed and further studies are necessary. Ultimately, specific eGFR equations for liver disease or novel methods for estimating GFR may be necessary. However, for now, the limitations of currently available methods need to be appreciated to understand renal function in liver disease.

Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies

“…Furthermore, in patients who are obese (body mass index >30 kg/m 2 ), creatinine‐based eGFR calculation using the MDRD and CKD‐EPI estimates underestimated GFR, whereas cystatin C–based measurement did not . Finally, while results have been mixed, some studies show improved estimation of GFR in severe liver disease because creatinine is biased by low creatine production and elevated bilirubin in these patients …”

“…In another case report, dosing of an aminoglycoside antibiotic cleared by the kidney corrected for eGFR‐creatinine resulted in overestimation of GFR, accumulation of the drug, and, ultimately, AKI in an elderly man. The patient also sustained liver injury, and studies have shown that in advanced liver disease, use of creatinine leads to an overestimation of GFR . To remedy this, cystatin C is recommended for more accurate GFR estimation and dosing guidance .…”

“…The patient also sustained liver injury, and studies have shown that in advanced liver disease, use of creatinine leads to an overestimation of GFR. 37 To remedy this, cystatin C is recommended for more accurate GFR estimation and dosing guidance. 67 Therefore, KDIGO encourages that for the safety of patients with CKD, in posology decisions regarding medications with a narrow therapeutic window, where precision is required, GFR estimations should use cystatin C if direct measurement is not available.…”

REnal Flow and Microstructure AnisotroPy (REFMAP) MRI in Normal and Peritumoral Renal Tissue

“…However, despite its utility as a low‐cost and widely accessible estimate of renal function, eGFR does not assess the laterality of dysfunction, differentiate pathophysiology, or predict recovery. The equations in current use overestimate eGFR in patients with comorbid liver disease, and have poor accuracy in populations with renal dysfunction but normal eGFR; for example, early in the course of diabetes …”

“…differentiate pathophysiology, or predict recovery. The equations in current use overestimate eGFR in patients with comorbid liver disease, 2 and have poor accuracy in populations with renal dysfunction but normal eGFR; for example, early in the course of diabetes. 3,4 Given the limitations of the established measures of renal function, there is a potential role for imaging.…”