Identifying patients at high risk of inappropriate drug dosing in periods with renal dysfunction

Introduction Dosing of renally cleared drugs in patients with kidney failure often deviates from clinical guidelines but little is known about what is predictive of receiving inappropriate doses. Methods and materials We combined data from the Danish National Patient Register and in-hospital data on drug administrations and estimated glomerular filtration rates for admissions between 1 October 2009 and 1 June 2016, from a pool of about 2.9 million persons. We trained artificial neural network and linear logistic ridge regression models to predict the risk of five outcomes (>0, ≥1, ≥2, ≥3 and ≥5 inappropriate doses daily) with index set 24 hours after admission. We used time-series validation for evaluating discrimination, calibration, clinical utility and explanations. Results Of 52,451 admissions included, 42,250 (81%) were used for model development. The median age was 77 years; 50% of admissions were of women. ≥5 drugs were used between admission start and index in 23,124 admissions (44%); the most common drug classes were analgesics, systemic antibacterials, diuretics, antithrombotics, and antacids. The neural network models had better discriminative power (all AUROCs between 0.77 and 0.81) and were better calibrated than their linear counterparts. The main prediction drivers were use of anti-inflammatory, antidiabetic and anti-Parkison’s drugs as well as having a diagnosis of chronic kidney failure. Sex and age affected predictions but slightly. Conclusion Our models can flag patients at high risk of receiving at least one inappropriate dose daily in a controlled in-silico setting. A prospective clinical study may confirm this holds in real-life settings and translates into benefits in hard endpoints.