Drugs and the kidney

The kidney plays a critical role in the elimination of many drugs from the body, hence consideration should be given to a patient’s renal function whenever any drug is prescribed. Much kidney disease is unrecognized, but the widespread reporting of estimated glomerular filtration rates (eGFR) has brought greater awareness of the prevalence of chronic kidney disease (CKD) and thereby encouraged medical practitioners to take account of reduced renal function when prescribing. CKD is very often one of many coexisting comorbid conditions, especially in elderly patients, when particularly careful thought must be given to appropriate drug dosing and the possibility of drug interactions.

A reduced GFR is the primary reason for reduced excretion of drugs in renal failure, but drug absorption, distribution, protein binding, metabolism, and pharmacodynamics may all be affected. Key general points are:

1 Both filtration and secretion of drugs appear to fall in parallel and in proportion to the GFR.

2 The clinical significance of a reduction in GFR and increased drug half-life depends on the relative importance of renal excretion and metabolism as a mode of elimination, and the therapeutic ratio of the drug.

3 If nonrenal clearance accounts for elimination of more than 50% of a drug, then no adjustment needs be made to dose or frequency of administration. Dosages of drugs which are mainly excreted in active form by the kidney (i.e. as unchanged drug or active metabolites) may need to be modified to avoid accumulation.

4 Potentially toxic drugs should only be used in patients with renal failure if there is a specific indication for their use and if therapy can be monitored appropriately. If dose adjustment is required, then dose, dose interval, or both can be adjusted to achieve the desired therapeutic profile.