Combining markers of nephrotoxicity and hepatotoxicity for improved monitoring and detection of chronic alcohol abuse.

BACKGROUND: Most of the commonly used markers of chronic alcohol abuse reflect alcohol hepatotoxicity; however, such abuse is deleterious to the kidneys as well. Combined use of serum markers of liver origin and urinary markers of kidney origin may be of diagnostic advantage. METHODS: The study was performed in 73 male alcoholics undergoing detoxification and 36 male alcoholics who had maintained abstinence for > or =6 weeks. Factor analysis, discriminant analysis and receiver operating characteristic (ROC) analysis were used to assess the discriminative power of two urinary markers of alcohol nephrotoxicity, namely beta-N-acetylhexosaminidase (Hex, EC 3.2.1.52) and alanine aminopeptidase (EC 3.4.11.2), and of three serum markers of alcohol hepatotoxicity, namely aspartate aminotransferase (EC 2.6.1.1), alanine aminotransferase (EC 2.6.1.2) and gamma-glutamyltransferase (GGT, EC 2.3.2.2), and of their quantitative combinations. RESULTS: The discriminative power of the urinary markers matched that of the serum markers. Hex and GGT appeared to be the best for discriminating the study groups. Their combination given by the equation G&H=0.62 x ln(GGT)+0.72 x ln(Hex) showed excellent discriminative ability (ROC area under the curve 0.92) that was significantly higher than that of any single marker in this report, indicating superior diagnostic accuracy of the compound marker. CONCLUSIONS: Kidney-derived urinary markers, particularly Hex, can complement or replace, if necessary, serum markers of chronic alcohol abuse that relate to alcohol hepatotoxicity. The compound marker proposed seems a promising tool for the monitoring and perhaps detection of chronic alcohol abuse and warrants further studies.

Alanine aminopeptidase activity in urine: a new marker of chronic alcohol abuse?

BACKGROUND: The purpose of this study was to evaluate the activity of urinary alanine aminopeptidase (AAP), the enzyme released from the brush border membranes of renal proximal tubules, as a new biological marker of chronic alcohol abuse. METHODS: The AAP activity was assayed and compared between a group of 76 alcoholics undergoing detoxification and a group of 37 alcoholics abstaining from alcohol for at least 6 weeks. In all patients, the enzyme activity was measured both in untreated urine (uAAP) and after removal of endogenous AAP inhibitors by molecular filtration on Sephadex (eAAP). RESULTS: There was a correlation between the uAAP and eAAP activities in both groups of patients (r = 0.61 and r = 0.81 in abstinent alcoholics and in alcoholics undergoing detoxification, respectively), and both the uAAP activity and the eAAP activity were significantly and markedly higher in alcoholics being detoxified than in their abstinent counterparts. As revealed by receiver operating characteristic analysis, the discriminative power of the eAAP activity assay was higher than that of the uAAP activity assay. The area under the corresponding receiver operating characteristic curves was 0.84 +/- 0.04 and 0.78 +/- 0.05 (mean +/- SE), respectively. CONCLUSIONS: The results of this study demonstrate that the assays of urinary AAP activity, which relate to the nephrotoxic effects of alcohol abuse, could be a valuable complement to the other presently used markers of chronic alcohol abuse that are generally based on ethanol hepatotoxicity. Compared with the uAAP activity test, the eAAP activity test is of clear diagnostic advantage.