RT Book, Section A1 Nolin, Thomas D. A2 Lerma, Edgar V. A2 Rosner, Mitchell H. A2 Perazella, Mark A. SR Print(0) ID 1149117506 T1 Clinical Pharmacology and the Kidney T2 CURRENT Diagnosis & Treatment: Nephrology & Hypertension, 2e YR 2017 FD 2017 PB McGraw-Hill Education PP New York, NY SN 9781259861055 LK accessmedicine.mhmedical.com/content.aspx?aid=1149117506 RD 2024/10/07 AB Patients with chronic kidney disease (CKD) typically are prescribed an extraordinarily high number of medications compared to individuals without kidney disease. This is due to the presence of numerous comorbidities, including cardiovascular, hematologic, endocrine, psychiatric, and mineral and bone disorders. Notably, patients with end-stage renal disease exhibit the highest medication burden, taking an average of 12 medications (prescribed and over-the-counter) with a median pill burden of 19 per day. All CKD patients are at high risk for developing medication-related problems, including adverse drug effects and drug interactions, leading to suboptimal therapeutic outcomes, and vigilance is required to optimize drug use. Many drugs are predominantly eliminated by the kidney and can accumulate in CKD patients, and even those that are predominantly nonrenally cleared (ie, undergo hepatic metabolism) may require dose adjustment to maximize therapeutic outcomes and to minimize adverse events. As a general rule, if 30% or more of a drug is eliminated unchanged by the kidney, then it will likely require dosage regimen adjustment in CKD patients, especially those with advanced kidney disease (stages 3–5 CKD). A firm knowledge of general principles of pharmacokinetics, and especially of the effects of kidney disease on drug disposition, together with a basic understanding of processes to identify and resolve medication-related problems will facilitate improved drug selection, dosing and safety in all patients with impaired kidney function. This chapter presents clinically relevant pharmacokinetic and pharmacodynamic alterations commonly observed in patients with CKD, provides pragmatic approaches for proactively adjusting drug dosage regimens in these patients, and briefly discusses important medication safety considerations.