A Quantitative Approach to Drug Dosing in Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is increasing at an alarming rate. Medication prescribing in this growing population is especially difficult. Many pharmacological agents or their metabolites are eliminated unchanged through the kidney. Drug dosing in CKD is challenging as most patients have a number of comorbid conditions. Patients with CKD take pharmacological agents with potential for drug interactions. Most patients also have alterations to the normal functioning of a number of different organs or systems (e.g. heart, liver, gastrointestinal system) which affect pharmacokinetics of commonly used drugs in CKD. Pharmacokinetic behaviors of most drugs are highly variable in patients with CKD. In addition, pharmacological management of patients with CKD is imprecise and requires estimating renal function, applying clinical judgment and, if available, therapeutic drug monitoring to provide adequate pharmacotherapeutic concentrations to optimize pharmacodynamic response while minimizing toxicities. For drugs that are removed through the renal system unchanged, a dosing modification should be considered according to patient- and drug-specific factors. Renal replacement therapy and dialysis remove pharmacologic agents extensively, and thus a replacement dose is needed to avoid therapeutic failure. By applying a quantitative approach, health care providers can improve pharmacotherapeutic outcomes while reducing adverse drug reactions.

Dose adjustment guidelines for medications in patients with renal impairment: how consistent are drug information sources?

“…2,3 Impaired renal function can have pronounced effects on the pharmacokinetics of many drugs as a result of alterations in glomerular filtration, tubular secretion, reabsorption or metabolism. 4 Therefore, there is an increased risk of drug-related problems such as the use of contraindicated drugs and inappropriate doses, with potential adverse outcomes. 5,6 It is essential to select the proper drug and individualise the dosage in order to avoid the occurrence of adverse events.…”

Renal drug dosing recommendations: evaluation of product information for brands of the same drug

“…Impaired renal function can be associated with alterations in drug absorption, protein binding, metabolism and excretion. Therefore, it is essential to individualise the dosage of many drugs in order to avoid toxicity and the risk of therapeutic failure . The renal function of the patient should be considered when prescribing drugs that are eliminated, unchanged by the kidneys, particularly those (i) with a narrow therapeutic index, (ii) with active metabolites that are primarily excreted by the kidney, or (iii) that are nephrotoxic.…”

The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies

“…Chronic kidney disease (CKD) can adversely affect the pharmacokinetics (PK) or pharmacodynamics (PD) of some therapies. 1 Thus, in order for clinicians to make informed choices, it is important to understand how: 1) the use of glucose-lowering therapies is affected by renal impairment; 2) treatment regimens may need to be modified and how these treatments may impact on CKD outcomes; and 3) the importance of safety across the spectrum of CKD.…”