Correction of Urine Cotinine Concentrations for Creatinine Excretion: Is It Useful?

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The validity of plasma or serum cotinine concentrations as a marker and stable measure of chronic nicotine intake is well documented (1)(2)(3)(4)(5)(6). Although considerably less exact as a measure of cigarette consumption (2)(4), cotinine concentrations are often used for that purpose as well. Applications include screening of individuals before recruitment into research studies and smoking cessation clinical trials, as an outcome marker of treatment efficacy, and for evaluation of adequacy of dosage in conjunction with nicotine replacement therapy (7). Measurement of salivary or spot urinary cotinine concentrations is frequently selected as a noninvasive alternative to blood-derived assays for reasons of logistics, cost, and subject retention (6)(8)(9)(10). As has been done with other analytes, urine cotinine-to-creatinine concentration ratios are commonly determined to correct for dilutional effects (6)(11)(12)(13), although a recent review of markers for tobacco use suggests that this step might be unnecessary (10).

Considering the disparate renal handling of cotinine and creatinine (14), we were interested in determining whether this additional laboratory procedure and calculation was justified. Because spot urinary cotinine measurements are often used as a surrogate for serum cotinine determinations, we investigated how well spot urinary cotinine measurements correlated with concurrent serum concentrations in smokers, and whether normalizing for urine creatinine concentration improved the relationship.