Chronic Kidney Disease

Drug Use in Renal Disease

Despite the British National Formulary (BNF) appendix on renal impairment, prescribing in renal disease remains a challenging area of practice.  As this can be an unforgiving area, it may often be wise to seek expert support when uncertain.  This section gives a brief overview of the key renal changes which impact on drug selection and dosing, explains some of the therapeutic issues which must be considered and highlights key medications which are likely to require a cautious approach.  Some practical points to consider are also included.

 Key Renal Changes

What the kidney does

 The kidneys are important for the regulation of the volume and chemical composition of the blood (and hence the internal environment) by selectively excreting products and water.  The kidney is also the major organ in the body responsible for excretion of most drugs. In renal disease, a number of changes occur in the way in which drugs are handled. These may be changes in the way the body handles the drug (pharmacokinetics) or changes in the way the body acts on the drug (pharmacodynamics). In renal terms, this comes down to

a) how does the degree of kidney impairment affect the handling, safety and effectiveness of the drug

b) does the drug have the potential to worsen the degree of renal impairment and

c) does the drug have the potential to exacerbate complications of renal failure.

Drug Selection and Dosing

 Getting the dose right

 Changes in doses of drugs in renal impairment depends on the severity of renal impairment. Use the eGFR reported as a guide. The British National Formulary offers initial advice on the prescribing of drugs in renal impairment (Appendix 3: Renal impairment). It defines renal impairment as mild (20-50ml/minute), moderate (10-20ml/minute) and severe (<10ml/minute). Both loading and maintenance doses may need to be adjusted.

The Renal Top 5 - drugs to take care with
 

Non steroidal antiinflammatories

Opiates

Pain relief The issue of prescribing analgesia in renal impairment is an important one. Paracetamol and nefopam are generally considered to be ‘safe’ analgesics to use in renal impairment, although nefopam can cause confusion and seizures. Non-Steroidal Anti-Inflammatory drugs can induce renal impairment and should only be used in severe renal impairment that is irreversible. Weak and strong opioid analgesics can accumulate significantly in renal impairment to produce toxic effects such as respiratory depression. So called mild opiates such as DF118 and codeine are amongst the worst offenders.

Spironolactone

Spironolactone is back in vogue following the publication of RALES. What is clear is that this has led to a rise in hospital admissions with life threatening hyperkalaemia. It is also associated with acute renal failure. It should therefore be avoided in patients with an eGFR below 45 mls/min, and carefully evaluated at eGFR between 60 and 45. Patients should be advised to consult their GP if they suffer an intercurrent illenss that may cause intravascular depletion - e.g. D&V - since this may precipitate a metabolic crisis.

ACEi and ARB

Love them or hate them, nephrologists cannot do without them. However they do need to handled with care. Guidance notes can be found here.

Trimethoprim

Trimethoprim is a well loved antibiotic. However it is a potent tubular poison, and can cause hyperkalaemia. If a patient has an eGFR below 60 it should be used with caution, especially if patients are on conventional potassium retaining agents - this may require monitoring. Trimethoprim can also impair creatinine excretion, and a rise in serum creatinine is common - this is NOT a decline in true GFR, but reflects the blockade of the active excretion of creatinine in the tubule.

Metformin

This should be used with caution in people with an eGFR below 60, and probably avoided when the eGFR is less than 45. Once the eGFR falls to 30 metformin should not be used. Lactic acidosis is a serious complication and is more common in patients with renal impairment. Patients who are stable and safe on metformin can develop problems if other agents that affect GFR are introduced (e.g. NSAID, volume depletion from diuretics).

Other Drugs

So many to choose from! This list will be added to as people feedback.

Dialysis patients

For patients with severe renal impairment who are receiving renal replacement therapies, for example haemodialysis or peritoneal dialysis, the responsibility for prescribed drugs often lies in secondary care. Renal replacement therapy can alter the rate of elimination of the drug. Advice on prescribing in renal impairment can also be obtained from local pharmacists and your Medicine Information Centres. The Renal Drug Handbook (edited by and available from the UK Renal Pharmacy Group) is an invaluable source of information too. In general, dosage adjustments in renal replacement therapies are only required for those drugs that require adjustment in renal failure i.e. if the manufacturer’s summary of product characteristics states no change in doses are required in renal failure, then the same is true for renal replacement therapy. No renal replacement therapy is as effective as normal kidneys over a 24 hour period so doses equal to or lower than those used in normal renal function should be given. However, it is wise to consult if you are unsure about drug usage in patients receiving either dialysis or with a renal transplant in situ.