LAUSR

Background Polypharamacy is common among patients with chronic kidney disease (CKD), but little is known about urinary excretion of many drugs and their metabolites among CKD patients. Methods To evaluate self-reported medication use in relation to urine drug metabolite levels in a large cohort of CKD patients, the Germany Chronic Kidney Disease study, we ascertained self-reported use of 158 substances and 41 medication groups and coded active ingredients according to the Anatomical Therapeutic Chemical classification system. We used a nontargeted mass spectrometry-based approach to quantify metabolites in urine; calculated specificity, sensitivity, and accuracy of medication use and corresponding metabolite measurements; and used multivariable regression models to evaluate associations and prescription patterns. Results Among 4885 participants, there were 108 medication-drug metabolite pairs based on reported medication use and 78 drug metabolites. Accuracy was excellent for measurements of 36 individual substances in which the unchanged drug was measured in urine (median, 98.5%; range 61.1%-100%). For 66 pairs of substances and their related drug metabolites, median measurement-based specificity and sensitivity were 99.2% (range 84.0%-100%) and 71.7% (range 1.2%-100%), respectively. Commonly prescribed medications for hypertension and cardiovascular risk reduction-including angiotensin-II receptor blockers, calcium channel blockers, and metoprolol-showed high sensitivity and specificity. Although self-reported use of prescribed analgesics (acetaminophen, ibuprofen) was <3% each, drug metabolite levels indicated higher usage (acetaminophen, 10%-26%; ibuprofen, 10%-18%). Conclusions This comprehensive screen of associations between urine drug metabolite levels and self-reported medication use supports the use of pharmacometabolomics to assess medication adherence and prescription patterns in persons with CKD, and indicates underreported use of medications available over the counter, such as analgesics.