Consensus definitions of renal function in hepatorenal syndrome (HRS) are inconsistent – excellent potential of MDRD calculated glomerular filtration rate

Background and Aims: Discrimination of HRS type 1, associated with an ominous progno-sis from HRS type 2 and, moreover from normal renal function is of great clinical importance in patients with cirrhosis. The consensus definition (Hepatology 1996;23:164–176) of HRS type 1 comprises a serum creatinine concentration (Crea) above 2.5mg/100ml or a creatinine clearance (CrCl) below 20ml/min with cut-off values for normal renal function of 1.5mg/100ml or 40ml/min. Unfortunately, most studies on renal function in cirrhosis excluded pts. with HRS and the accordance of the cut-off values above has not been investigated. Aim of the present study was the comparison of Crea with measured CrCl and with the glomerular filtration rate calculated by the MDRD formula incorporating age, sex and race (GFRm), recently suggested to accurately reflect GFR (Clin Chem 2006;52:5–18).

Methods: 143 samples of serum and 24hrs collected urine from hospitalized pts. with cirrhosis and various degrees of renal impairment were analyzed. Crea was determined by a rate blanked modified Jaffe' reaction.

Results: According to consensus Crea cut-off values, there were 15 HRS type 1, 19 HRS type 2 and 109 without HRS. CrCl (median;range) in HRS type 1 was 11 (4–42)ml/min with 2 above 20ml/min and in pts without HRS 70 (13–199)ml/min with 17 below 40ml/min. GFRm was 18 (13–25)ml/min and 90 (39–163)ml/min, respectively. Applying ROC analysis best cut-off values for diagnosis of HRS type 1 were 27.5ml/min for CrCl (AUC 0.95) and 26.5ml/min for GFRm (AUC 1.0). For the exclusion of any HRS (type 1 and type 2) GFRm had the best cut-off at 49ml/min (AUC 0.97), CrCl at 28.5ml/min (AUC 0.92). Thus, the margin of cut-off values between “HRS type 1“ and “exclusion of HRS“ was much wider and thus apparently superior for GFRm than for CrCl. Correlations of GFRm were r=0.92 with 1/Crea and r=0.59 with CrCl.

Conclusion: This is the first study with a large number of patients to compare established cri-teria of renal failure in HRS. Cut-off values of Crea and CrCl were found to be inconsistent. GFRm allows for excellent discrimination of patients with HRS type 1 and without HRS, respectively. GFRm should therefore be further investigated in prospective trials on HRS.