SYSTEMATIC REVIEW OF MEASURED CREATININE CLEARANCE (MCCREA) AS A MARKER OF GLOMERULAR FILTRATION IN PATIENTS WITH LIVER CIRRHOSIS

N Proulx, H Clark, A Akbari, A Rostom

University of Ottawa, Ontario

BACKGROUND: Adequate assessment of glomerular filtration rate (GFR) in patients with liver cirrhosis is essential for proper dosing of drugs (ie diuretics) as well as the detection and monitoring of chronic renal disease. Serum creatinine fails to rise in liver cirrhosis even with severe renal impairment and this may be related to a marked decrease in the production of hepatic creatine. Recent articles demonstrated significant overestimation of GFR (gold standard being inulin clearance [CIn]) by MCCrea as shown by reported positive MCCrea/CIn ratios. Furthermore the extent of this overestimation may be dependant on liver cirrhosis severity. The aim of this study was to perform a systematic review aimed at evaluating MCCrea as a marker of GFR when compared to the GFR gold standard CIn in stable patients with liver cirrhosis of varying severity.
METHOD: Potentially relevant, manually searched, English, French, Italian and Spanish articles were identified from the Medline, Old medline, Index medicus and Cochrane library databases. Inclusion/exclusion criteria were applied on the potentially relevant articles by two independent reviewers. Data was pooled by retrieving the values from the graphs of individual articles.
RESULTS: The 7 articles describe a homogeneous stable group of 193 predominantly male (79%) patients with weighted mean age of 56.1 years. The majority (81%) were in a decompensated Child class B or C with 50 % having either a posthepatitic or postviral cause to their cirrhosis. Controlled studies do not show a relationship between MCCrea/CIn and liver cirrhosis severity. For the total population, the Pearson correlation coefficient (r) = 0.78 (p< 0.001) and Intraclass correlation coefficient (ICC) = 0.87 (95%CI 0.82-0.90). For the subgroup with GFR < 60 ml/min, r = 0.72 (p<0.001), ICC = 0.75 (95%CI 0.59-0.85) and the mean difference (MD) [Bland method] = 8.1 ml/min (95% CI -20.3 - 40.4). For the subgroup with GFR > 60 ml/min, r = 0.52 (p<0.001), ICC = 0.66 (95%CI 0.52-0.75) and MD = 15.3 ml/min (95% CI -37.2 - 67.8).
CONCLUSION: GFR overestimation by MCCrea is not influenced by liver cirrhosis severity. MCCrea may be a worse indicator of GFR in patients without renal disease (GFR>60 ml/min) when compared to those with renal disease (GFR<60 ml/min). At higher GFR values the substantial lack of agreement between MCCrea and CIn may not justify their interchangeable use and novel GFR markers are therefore needed in this patient population.