Urine-creatinine concentration as a marker of urine dilution: reflections using a cohort of 45,000 samples.

BACKGROUND: Statistical data from a wide cohort of subjects should provide arguements for a more valid interpretation of urine-creatinine concentrations as laboratory marker of urine dilution. METHODS: Unselected, consecutive urine-creatinine concentrations from 11,811 women and 13,009 men in a clinical chemistry laboratory (mainly from clinical trials and employment medicine departments) and from 7300 women and 12,456 men in a toxicological chemistry laboratory (mainly from drug screenings for re-issuing drivers licenses or from employment medicine departments) were evaluated by descriptive and comparative statistics. RESULTS: Women (clinical chemistry lab, toxicological chemistry lab): mean 723 mg/L, 921 mg/L; median 568 mg/L, 728 mg/L; 2.5-97.5% percentile range 189-2198 mg/L, 129-2690 mg/L. Men (clinical chemistry lab, toxicological chemistry lab): mean 975 mg/L, 1395 mg/L; median 802 mg/L, 1241 mg/L; 2.5-97.5% percentile range 256-2660 mg/L, 204-3520 mg/L. The rate of urine-creatinine concentrations of >3000 mg/L (up to 3-fold of the upper limit of the reference range) was higher for men in both laboratories and for both genders in the toxicological chemistry lab compared with the clinical chemistry lab (toxicological chemistry lab: 697 for men (5.6%) and 111 for women (1.5%), clinical chemistry lab: 200 for men (1.5%) and 93 for women (0.8%)). CONCLUSIONS: Utmost caution should be taken when interpreting urinary creatinine concentrations that fall below so-called cut-offs. Cut-offs greater than the gender-specific 2.5% percentiles bear a high risk of misinterpretation regarding urine adulteration. Such cut-offs are no longer acceptable. At present, the borderline range of >50mg/L to <200mg/L given by the Australian Standard AS/NZS4308:2008 and indicating dilute urines but are not implicated in adulteration seems to fit best with the clinical and forensic requirements. Nevertheless, using gender-independent urine-creatinine concentration cut-offs can discriminate women since women have in general lower muscle mass and thus lower urinary creatinine concentrations compared with men. Future concepts of drug screen in urine should use gender-specific and creatinine-adjusted decision limits.