Medicines and the kidneys

Last updated: Friday, August 03, 2018

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:

Cross-section of the kidney

1. Excretion

Reduced renal clearance of drugs in renal impairment is an important factor when considering dosage adjustments. A fall in renal drug clearance usually indicates a reduction in the number of functioning nephrons.

Apart from the parent drug, many active or toxic drug metabolites depend upon the kidney for elimination. 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.

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. 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 failure 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.