Combining markers of nephrotoxicity and hepatotoxicity for improved monitoring and detection of chronic alcohol abuse
-
Ewa Taracha
Abstract
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 ≥6weeks. 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 β-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 γ-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×ln(GGT)+0.72×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.
Clin Chem Lab Med 2006;44:1446–52.
References
1. Alling C, Chick JD, Anton R, Mayfield RD, Salaspuro M, Helander A, et al. Revealing alcohol abuse: to ask or to test? Alcohol Clin Exp Res 2005; 29:1257–63.10.1097/01.ALC.0000171489.55856.A5Search in Google Scholar
2. Conigrave KM, Davies P, Haber P, Whitfield JB. Traditional markers of excessive alcohol use. Addiction 2003; 98(Suppl 2):31–43.10.1046/j.1359-6357.2003.00581.xSearch in Google Scholar
3. Helander A. Biological markers in alcoholism. J Neural Transm 2003; 110(Suppl 66):15–22.10.1007/978-3-7091-0541-2_2Search in Google Scholar
4. Reynaud M, Schellenberg F, Loiseaux-Meinier MN, Schwan R, Maradeix B, Planche F, et al. Objective diagnosis of alcohol abuse: compared values of carbohydrate-deficient transferrin (CDT), γ-glutamyl transferase (GGT) and mean corpuscular volume (MCV). Alcohol Clin Exp Res 2000; 24:1414–19.Search in Google Scholar
5. Helander A, Fors M, Zakrisson B. Study of Axis-Shield new %CDT immunoassay for quantification of carbohydrate-deficient transferrin (CDT) in serum. Alcohol Alcohol 2001; 36:406–12.10.1093/alcalc/36.5.406Search in Google Scholar
6. Schwan R, Albuisson E, Malet L, Loiseaux MN, Reynaud M, Schellenberg F, et al. The use of biological laboratory markers in diagnosis of alcohol misuse: an evidence-based approach. Drug Alcohol Depend 2004; 74:273–9.10.1016/j.drugalcdep.2004.01.002Search in Google Scholar
7. Godart B, Mennetrey L, Schellenberg F, Pages JC, Bacq Y. Carbohydrate-deficient transferrin and γ-glutamyl transpeptidase in the evaluation of alcohol consumption. A five-year retrospective study of 633 outpatients in a single center. Gastroenterol Clin Biol 2005; 29:113–6.10.1016/S0399-8320(05)80712-2Search in Google Scholar
8. Koch H, Meerkerk GJ, Zaat JO, Ham MF, Scholten RJ, Assendelft WJ. Accuracy of carbohydrate-deficient transferrin in the detection of excessive alcohol consumption: a systematic review. Alcohol Alcohol 2004; 39:75–85.10.1093/alcalc/agh031Search in Google Scholar
9. Salaspuro M. Carbohydrate-deficient transferrin as compared to other markers of alcoholism: a systematic review. Alcohol 1999; 19:261–71.10.1016/S0741-8329(99)00044-0Search in Google Scholar
10. Hock B, Schwarz M, Domke I, Grunert VP, Wuertemberger M, Schiemann U, et al. Validity of carbohydrate-deficient transferrin (%CDT), γ-glutamyltransferase and mean corpuscular erythrocyte volume (MCV) as biomarkers for chronic alcohol abuse: a study in patients with alcohol dependence and liver disorders of non-alcoholic and alcoholic origin. Addiction 2005; 100:1477–86.10.1111/j.1360-0443.2005.01216.xSearch in Google Scholar PubMed
11. Anton RF, Lieber C, Tabakoff B. Carbohydrate-deficient transferrin and γ-glutamyltransferase for the detection and monitoring of alcohol use: results from a multisite study. Alcohol Clin Exp Res 2002; 26:1215–22.Search in Google Scholar
12. Chen J, Conigrave KM, Macaskill P, Whitfield JB, Irving L. Combining carbohydrate-deficient transferrin and γ-glutamyltransferase to increase diagnostic accuracy for problem drinking. Alcohol Alcohol 2003; 38:574–82.10.1093/alcalc/agg113Search in Google Scholar PubMed
13. Yersin B, Nicolet JF, Dercrey H, Burnier M, van Melle G, Pecoud A. Screening for excessive alcohol drinking. Comparative value of carbohydrate-deficient transferrin, γ-glutamyltransferase, and mean corpuscular volume. Arch Int Med 1995; 155:1907–11.10.1001/archinte.1995.00430170103013Search in Google Scholar
14. Conigrave KM, Degenhardt LJ, Whitfield JB, Saunders JB, Helander A, Tabakoff B. CDT, GGT, and AST as markers of alcohol use: The WHO/ISBRA collaborative project. Alcohol Clin Exp Res 2002; 26:332–9.10.1111/j.1530-0277.2002.tb02542.xSearch in Google Scholar
15. Chan AW. Biochemical markers for alcoholism. In: Windle M, Searles JS, editors. Children of alcoholics: critical perspectives. New York: Guilford Press, 1990:39–71.Search in Google Scholar
16. Harasymiw J, Seaberg J, Bean P. Detection of alcohol misuse using a routine test panel: the early detection of alcohol consumption (EDAC) test. Alcohol Alcohol 2004; 39:329–35.10.1093/alcalc/agh061Search in Google Scholar
17. Sillanaukee P, Massot N, Jousilahti P, Vartiainen E, Poikolainen K, Olsson U, et al. Enhanced clinical utility of γ-CDT in a general population. Alcohol Clin Exp Res 2000; 24:1202–6.Search in Google Scholar
18. Sillanaukee P, Olsson U. Improved diagnostic classification of alcohol abusers by combining carbohydrate-deficient transferrin and γ-glutamyltransferase. Clin Chem 2001; 47:681–5.10.1093/clinchem/47.4.681Search in Google Scholar
19. Hultberg B, Isaaksson A, Tiderström G. β-Hexosaminidase, leucine aminopeptidase, hepatic enzymes and bilirubin in serum of chronic alcoholics with acute ethanol intoxication. Clin Chim Acta 1980; 105:317–23.10.1016/0009-8981(80)90111-4Search in Google Scholar
20. Kärkkäinen P, Jokelainen K, Roine R, Suokas A, Salaspuro M. The effects of moderate drinking and abstinence on serum and urinary β-hexosaminidase levels. Drug Alcohol Depend 1990; 25:35–8.10.1016/0376-8716(90)90137-4Search in Google Scholar
21. Taracha E, Habrat B, Chmielewska K, Baran H, Szukalski B. The activity of β-hexosaminidase (uHex) and γ-glutamyltransferase (uGGT) in urine as non-invasive markers of chronic alcohol abuse. II. Opiate-dependent subjects receiving methadone substitution. World J Biol Psychiatry 2002; 3:44–9.10.3109/15622970209150600Search in Google Scholar
22. Taracha E, Habrat B, Woźniak P, Walkowiak J, Szukalski B. The activity of β-hexosaminidase (uHex) and γ-glutamyltransferase (uGGT) in urine as non-invasive markers of alcohol abuse. I. Alcohol-dependent subjects. World J Biol Psychiatry 2001; 2:184–9.10.3109/15622970109026807Search in Google Scholar
23. Kärkkäinen P, Salaspuro M. β-Hexosaminidase in the detection of alcoholism and heavy drinking. Alcohol Alcohol 1991; 26(Suppl 1):459–64.Search in Google Scholar
24. Taracha E, Habrat B, Lehner M, Wisłowska A, Woronowicz BT, Bogulas M, et al. Alanine aminopeptidase (AAP) activity in urine: a new marker of chronic alcohol abuse? Alcohol Clin Exp Res 2004; 28:729–35.10.1097/01.ALC.0000125347.93779.81Search in Google Scholar
25. World Health Organization. The ICD-10 classification of mental and behavioural disorders: criteria for research. Geneva: WHO, 1993.Search in Google Scholar
26. Maruhn D. Rapid colorimetric assay of β-galactosidase and N-acetyl-β-glucosaminidase in human urine. Clin Chim Acta 1976; 73:453–61.10.1016/0009-8981(76)90147-9Search in Google Scholar
27. Jung K, Scholz D. An optimized assay of alanine aminopeptidase activity in urine. Clin Chem 1980; 26:1251–4.10.1093/clinchem/26.9.1251Search in Google Scholar
28. Wensing G, Neumann U, Ohnhaus EE, Heidemann HT. Effect of antipyrine and phenobarbital on renal γ-glutamyltransferase excretion in human urine. Clin Pharmacol Ther 1990; 48:575–81.10.1038/clpt.1990.194Search in Google Scholar
29. Mattenheimer H, Maruhn D. Preanalytical treatment of urine. In: Jung K, Mattenheimer H, Burchardt U, editors. Urinary enzymes in clinical and experimental medicine. Berlin: Springer Verlag, 1992:89–95.Search in Google Scholar
30. Matteucci E, Giampietro O. To store urinary enzymes: how and how long? Kidney Int 1994; 46(Suppl 47):58–9.Search in Google Scholar
31. Kairisto V, Poola A. Software for illustrative presentation of basic clinical characteristics of laboratory tests – Graph ROC for Windows. Scand J Clin Lab Invest 1995; 55(Suppl 222):43–60.10.3109/00365519509088450Search in Google Scholar
32. Grzybowski M, Younger JG. Statistical methodology: III. receiver operating characteristic curves. Acad Emerg Med 1997; 4:818–26.10.1111/j.1553-2712.1997.tb03793.xSearch in Google Scholar
33. Martinez LD, Barón AE, Helander A, Conigrave KM, Tabakoff B. The effect of total body water on the relationship between alcohol consumption and carbohydrate-deficient transferrin. Alcohol Clin Exp Res 2002; 26:1097–104.10.1111/j.1530-0277.2002.tb02644.xSearch in Google Scholar
34. Sillanaukee P, Strid N, Allen JP, Litten RZ. Possible reasons why heavy drinking increases carbohydrate-deficient transferrin. Alcohol Clin Exp Res 2001; 25:34–40.10.1111/j.1530-0277.2001.tb02124.xSearch in Google Scholar
35. Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 1993; 39:561–77.10.1093/clinchem/39.4.561Search in Google Scholar
36. Walter H, Hertling I, Benda N, Konig B, Ramskogler K, Riegler A, et al. Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patients. Alcohol 2001; 25:189–94.10.1016/S0741-8329(01)00188-4Search in Google Scholar
37. Brenner H, Gefeller O. Variation of sensitivity, specificity, likelihood ratios and predictive values with disease prevalence. Stat Med 1997; 16:981–91.10.1002/(SICI)1097-0258(19970515)16:9<981::AID-SIM510>3.0.CO;2-NSearch in Google Scholar
38. Martines D, Morris AI, Gilmore IT, Ansari MA, Patel A, Quayle JA, et al. Urinary enzyme output during detoxification of chronic alcoholic patients. Alcohol Alcohol 1989; 24:113–20.10.1093/oxfordjournals.alcalc.a044874Search in Google Scholar
39. Anttila P, Järvi K, Latvala J, Romppanen J, Punnonen K, Niemelä O. Biomarkers of alcohol consumption in patients classified according to the degree of liver disease severity. Scand J Clin Lab Invest 2005; 65:141–51.10.1080/00365510510013532Search in Google Scholar PubMed
40. Schellenberg F, Schwan R, Mennetrey L, Loiseaux MN, Pages JC, Reynaud M. Dose-effect relation between daily ethanol intake in the range 0–70 grams and %CDT value: validation of a cut-off value. Alcohol Alcohol 2005; 40:531–4.10.1093/alcalc/agh194Search in Google Scholar PubMed
41. Hermida J, Casal JA, Tutor JC. Effect of partial proteolysis on the activation energy of β-N-acetylhexosaminidase precursor and mature forms. Clin Chem Lab Med 2003; 41:302–5.10.1515/CCLM.2003.048Search in Google Scholar PubMed
©2006 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Initiation and progression of atherosclerosis – enzymatic or oxidative modification of low-density lipoprotein?
- Blood transfusions in athletes. Old dogmas, new tricks
- Molecular detection of tyrosinase transcripts in peripheral blood from patients with malignant melanoma: correlation of PCR sensitivity threshold with clinical and pathologic disease characteristics
- Increase in and clearance of cell-free plasma DNA in hemodialysis quantified by real-time PCR
- Lipoprotein lipase gene polymorphism at the PvuII locus and serum lipid levels in Guangxi Hei Yi Zhuang and Han populations
- Interpretation of cardiac troponin T behaviour in size-exclusion chromatography
- Point-of-care C-reactive protein testing in febrile children in general practice
- Improvement in HPLC separation of porphyrin isomers and application to biochemical diagnosis of porphyrias
- Measurement of late-night salivary cortisol with an automated immunoassay system
- Combining markers of nephrotoxicity and hepatotoxicity for improved monitoring and detection of chronic alcohol abuse
- Stone or stricture as a cause of extrahepatic cholestasis – do liver function tests predict the diagnosis?
- Insulin resistance and enhanced protein glycation in men with prehypertension
- Prevalence-dependent decision limits for the early detection of type 2 diabetes mellitus in venous blood, venous plasma and capillary blood during glucose challenge
- Analytical performance and clinical utility of the INNOTEST® PHOSPHO-TAU(181P) assay for discrimination between Alzheimer's disease and dementia with Lewy bodies
- Variations in assay protocol for the Dako cystatin C method may change patient results by 50% without changing the results for controls
- Approved IFCC recommendation on reporting results for blood glucose: International Federation of Clinical Chemistry and Laboratory Medicine Scientific Division, Working Group on Selective Electrodes and Point-of-Care Testing (IFCC-SD-WG-SEPOCT)
- National survey on the pre-analytical variability in a representative cohort of Italian laboratories
- 10% CV concentration for the fourth generation Roche cardiac troponin T assay derived from Internal Quality Control data
- Biological variation of non-SI traceable biological quantities: example of proteins
- Effect of tibolone therapy on lipids and coagulation indices
- Acknowledgement
- Contents Volume 44, 2006
- Author Index
- Subject Index
Articles in the same Issue
- Initiation and progression of atherosclerosis – enzymatic or oxidative modification of low-density lipoprotein?
- Blood transfusions in athletes. Old dogmas, new tricks
- Molecular detection of tyrosinase transcripts in peripheral blood from patients with malignant melanoma: correlation of PCR sensitivity threshold with clinical and pathologic disease characteristics
- Increase in and clearance of cell-free plasma DNA in hemodialysis quantified by real-time PCR
- Lipoprotein lipase gene polymorphism at the PvuII locus and serum lipid levels in Guangxi Hei Yi Zhuang and Han populations
- Interpretation of cardiac troponin T behaviour in size-exclusion chromatography
- Point-of-care C-reactive protein testing in febrile children in general practice
- Improvement in HPLC separation of porphyrin isomers and application to biochemical diagnosis of porphyrias
- Measurement of late-night salivary cortisol with an automated immunoassay system
- Combining markers of nephrotoxicity and hepatotoxicity for improved monitoring and detection of chronic alcohol abuse
- Stone or stricture as a cause of extrahepatic cholestasis – do liver function tests predict the diagnosis?
- Insulin resistance and enhanced protein glycation in men with prehypertension
- Prevalence-dependent decision limits for the early detection of type 2 diabetes mellitus in venous blood, venous plasma and capillary blood during glucose challenge
- Analytical performance and clinical utility of the INNOTEST® PHOSPHO-TAU(181P) assay for discrimination between Alzheimer's disease and dementia with Lewy bodies
- Variations in assay protocol for the Dako cystatin C method may change patient results by 50% without changing the results for controls
- Approved IFCC recommendation on reporting results for blood glucose: International Federation of Clinical Chemistry and Laboratory Medicine Scientific Division, Working Group on Selective Electrodes and Point-of-Care Testing (IFCC-SD-WG-SEPOCT)
- National survey on the pre-analytical variability in a representative cohort of Italian laboratories
- 10% CV concentration for the fourth generation Roche cardiac troponin T assay derived from Internal Quality Control data
- Biological variation of non-SI traceable biological quantities: example of proteins
- Effect of tibolone therapy on lipids and coagulation indices
- Acknowledgement
- Contents Volume 44, 2006
- Author Index
- Subject Index
