Optimizing therapeutics for hospitalized patients with impaired renal function

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DESCRIPTION (provided by applicant): A third of patients admitted to the hospital have underlying renal impairment or develop acute renal failure during their hospital course. The majority of these patients are prescribed a drug that is sensitive to renal function, and should be dose adjusted to avoid drug accumulation and toxicity. Over three decades of research has produced a variety of techniques to estimate renal clearance and other pharmacokinetic parameters which can instruct prescribers on how to adjust doses or frequencies of administration. However, few of these techniques are reliably applied by physicians or other providers, and inaccurate dosing in the setting of renal insufficiency has been identified as one of the major causes of preventable adverse drug events. Computerized prescriptions with automated guidance for prescribers will ultimately provide the safeguards and real-time assistance that is needed to prevent dosing errors. However, the existing implementations may not be sophisticated enough to offer accurate dosing recommendations. For example, the widely used Cockcroft-Gault estimate for renal clearance is inaccurate at the extremes of weight and age and with rapid changes in kidney function. All of these caveats are frequently present in hospitalized patients. It is unknown how many of the drug recommendations generated by a 'single-model1 approach would be altered if a more tailored, individualized approach was applied. We hypothesize that 3 major changes to a renal dose decision support system will substantially alter the guidance: 1) estimate drug clearance with a model tailored to patient characteristics 2) notification of changes to drug clearance which should alter existing drug therapy 3) apply medication-specific pharmacokinetic models to dose therapies with a narrow therapeutic range. We will test our hypothesis by simulating the performance of each redesigned component in a large dataset of patient and prescription data. Relevance to public health: Hospitalized patients with impaired kidney function need special care and monitoring to avoid drug accumulation and direct kidney toxicity. Computerized systems of care are needed to optimally assist with drug dosing and to assist physicians with maintaining vigilance when sudden changes in health status make prior drug dosing obsolete.