Medicines and the kidneys

Last updated: Tuesday, March 08, 2022

The way that a medicine behaves in the body can be strongly influenced by the kidney and any degree of reduced function it has. The kidney affects medicines in three principal ways:

1. Excretion

Most systemically administered drugs are eliminated at least partly by the kidney, even if it is only a small proportion of the dose. However, for some drugs, the kidney is the major site for elimination of unchanged drug and these are particularly liable to require careful dose adjustment in renal dysfunction to prevent accumulation. 

Examples of drugs principally eliminated unchanged by the kidney include:

In addition, there are drugs with therapeutic activity at least partly dependent upon metabolites that are excreted unchanged by the kidney. An example is allopurinol, which has an active metabolite called oxipurinol which works in the same way as the parent drug. Some drugs have toxic metabolites that are eliminated renally. For example nor-pethidine, a major metabolite of pethidine, can accumulate in renal failure to cause CNS toxicity such as convulsions. The high incidence of adverse drug reactions seen in patients with renal failure may be explained in part by the accumulation of drugs themselves or their metabolites.

The effectiveness of some drugs may be reduced with advancing renal impairment such as nitrofurantoin; inadequate urine concentrations may result in treatment failure when the GFR is <30mL/min.

Cross-section of the kidney

2.  Distribution and bioavailability

Renal insufficiency frequently alters the volume of distribution of drugs. Oedema or ascites may increase the apparent volume of distribution of highly water-soluble drugs (e.g. gentamicin). Higher doses may be needed to produce the desired therapeutic effect. Conversely dehydration or muscle wasting may result in unexpectedly high plasma concentrations of drugs.

Predicting the clinical consequences of altered protein binding in renal insufficiency is difficult. Plasma protein binding is decreased when plasma urea levels are high (uraemia) due to altered albumin affinity for the drug. Patients with chronic kidney disease may also have hypoalbuminaemia. Decreased binding results in more free drug being available at the site of action but a shorter half-life as more free drug can be metabolised and/or excreted.

Patients with uraemia are often more susceptible to drug effects (e.g. increased effect of CNS depressants due to increased permeability of the blood brain barrier).

3. Metabolism

The kidney is a site of metabolism in only two clinically important examples. The conversion of 25-hydroxycholecalciferol to the active form of vitamin D called 1,25-dihydroxycholecalciferol (calcitriol) takes place in the kidney, and this process is often impaired in patients with renal failure. Patients with renal disease requiring vitamin D supplementation should be given the hydroxylated derivatives: either alfacalcidol (1-alpha-hydroxycholecalciferol) or calcitriol.

The kidney is also a major site of insulin metabolism and so patients with diabetes and renal failure may require less insulin.