Evaluation of renal function in patients with cirrhosis: Where are we now?

Table 1 Summary of the results of the main studies which evaluated the performance of renal function markers and/or glomerular filtration rate estimates estimates comparatively to a reference method in patients with cirrhosis

Ref.	Number of patients	Reference method	Performance of the estimate(s)
Papadakis et al[25], 1987	23 (mGFR = 66)	Inulin	Difference between mean mGFR and ClCr and CG -24 and -52 mL/min respectively in group with decreased mGFR (+10 and +4 in patients with normal mGFR)
Caregaro et al[35], 1994	56 (mGFR = 86.7)	Inulin	Difference between mean mGFR and ClCr and CG -14.6 and -4.9 respectively. Mean overestimation was 51% and 40% respectively in patients with GFR < 80
Roy et al[36], 1998	30 (mGFR = 30)	Inulin	Mean relative overestimation 80% with ClCr when moderate to severe CKD
Orlando et al[37], 1999	20	Inulin	Mean relative overestimation of 4% and 23% respectively for ClCr and CG in Child C patients. Relative difference only +3% and -6% respectively in Child A patients
Woitas et al[26], 2000	44 (mGFR = 37)	Inulin	Sensitivity to detect GFR < 90, 85.7% and 28.5% respectively for elevated CysC and SCr
Demirtaş et al[27], 2001	26 (HRS) (mGFR = 33.5)	99Tc-DTPA	Difference between mean mGFR and ClCr +7
Orlando et al[28], 2002	36 (mGFR = 71.5)	Inulin	Mean overestimation was 75% and 30% respectively for CG and ClCr in patients with decreased GFR (14% and 9% in patients with normal GFR). Sensitivity to detect GFR < 72 were 73%, 23%, 53% and 86% respectively for elevated CysC and SCr, CG and ClCr
Gonwa et al[5], 2004	1447 (Pretransplant) (mGFR = 90.7)	125I-Iothalamate	P30 were 60.8% and 66.7% for respectively CG and MDRD4. Difference between means mGFR and CG and MDRD4 +23.5 and +21.9 respectively
Pöge et al[41], 2006	44 (mGFR = 35.3)	Inulin	Mean absolute bias and P30 was 51.7/4.5%, 48.3/6.8%, 33.3/11.4% and 33.9/13.6% for respectively CG, MDRD4, Hoek and Larsson GFR formula
MacAulay et al[42] 2006	57 (mGFR = 83)	99Tc-DTPAIohexol	Mean difference between formula and mGFR was lower for MDRD6 comparing with CG (+3.5 vs +15.4). However, mean absolute difference was high and similar (23.4 vs 23.6) and poor precision was found with both eGFR (root mean square error 31.5 vs 30.5 for respectively MDRD6 and CG)
Francoz et al[31], 2010	157 (mGFR = 85)	Inulin	Mean absolute bias ± SD was 17 ± 32, 16 ± 29 and 8 ± 22 for CG, MDRD4 and CKD-EPI respectively. In patients with GFR < 70, CKD-EPI bias rose to 19 ± 20
Rognant et al[6], 2010	148 (Alcoholic Cirrhosis) (mGFR = 77)		Median absolute bias ± SD and P30 was 23 ± 23/33.3% and 22 ± 20/40% for CG and MDRD4 respectively
Kim et al[43], 2011	89 (normal SCr) (mGFR = 73)	99Tc-DTPA	Difference between mean mGFR and ClCr, CG and MDRD6 was -14.4/+ 19.1 and -40.1 respectively. AUC of ROC to detect GFR < 60 was 0.721, 0.561, 0.463 and 0.659 for 1/CysC, ClCr, CG and MDRD6 respectively
Xirouchakis et al[47], 2011	74 (mGFR = 81.7)	51Cr-EDTA	Concordance correlation coefficient was 0.61, 0.38 and 0.46 for respectively MDRD4, Larsson and Hoek estimates. P30 was 64% for MDRD4 and 68% for Hoek.
Gerhardt et al[48], 2011	44 (mGFR = 35.3)	Inulin	Median absolute bias and P30 was 40.1/6.8% and 42.5/6.8% for respectively MDRD175 and CKD-EPI
De Souza et al[49], 2013	202 (Pretransplant) (mGFR = 83)	Inulin	Concordance correlation coeffcient and P30 was 0.75/78.7, 0.56/42.6, 0.62/56.4, 0.8/83.2 and 0.82/78.2 for respectively Hoek, MDRD175, CKD-EPI, CKD-EPI CysC and mixed CKD-EPI formula

Acronyms description can be found in the text. GFR: Glomerular filtration rate; HRS: Hepato-renal syndrome; CKD: Chronic kidney disease; CG: Cockcroft and Gault formula; SCr: Serum creatinine.

Table 2 Description of the characteristics of the studies used to develop the common glomerular filtration rate estimates

Name of the study	Number of patients	Country	Reference method	Marker(s)	Mean GFR	Comments
CG 1976	249	Canada	24 h ClCr	SCr	30-130	No normalization on BSA
						Male patients only in the population of the study
MDRD 1999	1628	United States	Renal clearance 125I-Iothalamate	SCr	39.8 ± 21.2	Characteristics of the study population:
						Male 60%
						Black patients 12%
						> 55 yr 42%
						Diabetic patients 6%
						Re-expressed in 2007 to be used with IDMS traceable creatinine assay (MDRD 175)
CKD EPI (PCr) 2009	8254	United States	Various (urinary clearance of exogenous markers)	SCr	68 ± 40	Characteristics of the study population:
						Male 57%
						Black patiens 32%
						> 65 yr 13%
						Diabetic patients 29%
Hoek 2003	123	The Nederlands	Renal clearance 125I-Iothalamate	CysC	Median = 81	Characteristics of the study population:
						Male 48%
						Median age 50 yr
						Diabetic patients 24%
CKDEPI (Cys C and mixed PCr + CysC) 2012	5352	United States	Various (urinary or plasma clearance of exogenous markers)	CysC alone and both CysC and SCr	68 ± 39	Characteristics of the study population:
						Male 58%
						Black patients 40%
						Age > 65 yr 13%
						Diabetic patients 32%
						Patients with BMI > 30 31%

Acronyms description can be found in the text. GFR: Glomerular filtration rate. CKD: Chronic kidney disease; CG: Cockcroft and Gault formula; BMI: Body mass index.