Estimation of Glomerular Filtration Rate in Patients With Cirrhosis by Using New and Conventional Filtration Markers and Dimethylarginines

Abstract

Background and Aims Equations used to estimate glomerular filtration rate (GFR) are not accurate in patients with cirrhosis. We aimed to develop a new equation to estimate the GFR in subjects with cirrhosis and compare its performance with chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C and creatinine-cystatin C equations, which were derived in populations without cirrhosis. Methods From 2010 through 2014, we measured GFR in 103 subjects with cirrhosis based on non-radiolabeled iothalamate plasma clearance. We measured blood levels of creatinine, cystatin C, beta-trace protein, beta-2 microglobulin, L-arginine, and symmetrical and asymmetrical dimethylarginines simultaneously with GFR. Multivariate linear regression analysis was performed to develop models to estimate GFR. Overall accuracy, defined by the root mean square error (RMSE) of our newly developed model to estimate GFR, was compared with that of the CKD-EPI equations. To obtain an unbiased estimate of our new equation to estimate GFR, we used a leave-one-out cross-validation strategy. Results After we considered all the candidate variables and blood markers of GFR, the most accurate equation we identified to estimate GFR included serum levels of creatinine and cystatin C, as well as patients' age, sex and race. Overall, the accuracy of this equation (RMSE=22.92) was superior to that of the CKD-EPI cystatin C equation (RMSE=27.27, P=0.004). Among subjects with cirrhosis and diuretic-refractory ascites, the accuracy of the equation we developed to estimate GFR (RMSE=19.36) was greater than that of the CKD-EPI cystatin C (RMSE=27.30, P=0.003) and CKD-EPI creatinine-cystatin C equations (RMSE=23.37, P=0.004). Conclusions We developed an equation that estimates GFR in subjects with cirrhosis and diuretic-refractory ascites with greater accuracy than the CKD-EPI cystatin C equation or CKD-EPI creatinine-cystatin C.

Comparison of creatinine and cystatin formulae with 51Chromium‐ethylenediaminetetraacetic acid glomerular filtration rate in patients with decompensated cirrhosis

“…Correlations between 51 Chr‐EDTA GFR and CKD‐EPI‐sCr‐cysC and Mindikoglu‐eGFR recently proposed by Mindikoglu et al . CKD‐EPI, chronic kidney disease–epidemiology; cysC, serum cystatin C; GFR, glomerular filtration rate; Mindikoglu‐eGFR, estimated GFR proposed by Mindikoglu et al .…”

“…CKD‐EPI, chronic kidney disease–epidemiology; cysC, serum cystatin C; GFR, glomerular filtration rate; INR, international normalized ratio; MDRD, Modification of Diet in Renal Disease; MELD, model for end‐stage liver disease; Mindikoglu‐eGFR, estimated GFR proposed by Mindikoglu et al . ; sCr, serum creatinine.…”

“… ‡ P values compare the performance of Mindikoglu‐eGFR with the other estimated GFRs equations. However, the P values for bias reflect difference in the location of bias, not the magnitude.…”

“…CKD‐EPI‐sCr‐cysC and the equation recently proposed by Mindikoglu et al . (Mindikoglu‐eGFR)], were calculated in each patient. Finally, measurement of GFR was assessed with 51 Chromium‐ethylenediaminetetraacetic acid ( 51 Chr‐GFR) by sampling blood, after intravenous injection of tracer over 1–2 min, at 2, 4, and 6 h. 51 Chr‐GFR was calculated using the slope‐intercept technique, correcting for body surface area, and the fast exponential curve recommended by the British Nuclear Medicine Society guidelines .…”

“…However, the latter formula has been developed in patients without liver disease, and thus, its performance in patients with cirrhosis needs further evaluation. More recently, a new sCr‐based and cysC‐based equation has been derived from patients with cirrhosis, but its accuracy has not been validated …”