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Drug Prescribing in Renal Impairment

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Assessment of renal function

Prescribing in renal impairment
Nephrotoxic drugs
Use of a dosage table
References

PatientPlus articles are written by UK doctors and are based on research evidence, UK and
European Guidelines. They are designed for health professionals to use, so you may find the
language more technical than the condition leaflets.

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Renal impairment may be acute or chronic - both of which can result in problems with
medications. Renal impairment may be the result of a variety of renal or systemic diseases,
such as diabetic nephropathy or systemic lupus erythematosus. Normal ageing results in a
decline in renal function due to loss of nephrons. When prescribing for elderly patients, it
should therefore be assumed that some degree of renal impairment exists[1, 2].If even mild
renal impairment is considered likely, renal function should be checked before prescribing any
drug which requires dose modification. Reasons for problems with medications in renal
impairment include:

Failure to excrete a drug or its metabolites.

Many side-effects being poorly tolerated by patients with renal impairment.
Some drugs ceasing to be effective when renal function is reduced.

Computerised alerts are likely to become more important in reducing errors of prescribing in
patients with renal impairment[3, 4].

Assessment of renal function[5]

See separateAssessing Renal Functionarticle.

Normal GFR is approximately 100 ml/minute/1.73 m2.

Since April 2006 in the UK, most local laboratories calculate estimated glomerular
filtration rate (eGFR) on all samples sent for creatinine measurement.

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Prescribing in renal impairment

Drugs that are renally excreted may need to have their doses reduced in patients with
renal insufficiency or end-stage kidney disease:
For prescribing purposes, renal impairment is usually divided into three grades:
Mild: GFR 20-50 ml/minute; serum creatinine approximately 150-300 mol/L.
Moderate: GFR 10-20 ml/minute; serum creatinine approximately 300-700
mol/L.
Severe: GFR less than 10 ml/minute; serum creatinine >700 mol/L.
Patients with a GFR above 50 ml/minute do not usually require any dosage
adjustment.
Nephrotoxic drugs should, if possible, be avoided in patients with renal disease
because the consequences of nephrotoxicity are likely to be more serious when
the renal reserve is already reduced.
 The situation may change if a patient begins dialysis, since some drugs will be
removed by the dialysis. Dialysis may lead to the loss of therapeutic effect for some
drugs.
Drugs to which particular attention must be given include many antibiotics,
histamine H2-receptor antagonists, digoxin, anticonvulsants and non-steroidal anti-
inflammatory drugs (NSAIDs).
For many drugs with only minor or no dose-related side-effects very precise modification
of the dose regimen is unnecessary and a simple scheme for dose reduction is sufficient.
For more toxic drugs with a small safety margin, dose regimens based on GFR should be
used.
The total daily maintenance dose of a drug can be reduced either by reducing the size of
the individual doses or by increasing the interval between doses. For some drugs, if the
size of the maintenance dose is reduced it will be important to give a loading dose if an
immediate effect is required. The loading dose should usually be the same size as the
initial dose for a patient with normal renal function.

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Drugs causing biochemical changes

Prescribing any drug that increases potassium levels is potentially very dangerous - eg,
potassium supplements and potassium-sparing diuretics. Other products that contain
potassium include ispaghula husk laxatives.
Products with a high sodium content (eg, some antacids) may cause sodium and water
retention in patients with renal impairment.
Excessive vitamin D replacement therapy can cause hypercalcaemia that may precipitate
or exacerbate renal impairment. Many patients with chronic kidney disease (CKD) are
prescribed alfacalcidol; therapy should therefore be closely monitored.

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Nephrotoxic drugs
Drugs causing prerenal damage

Drugs that cause excessive gastrointestinal losses, either through diarrhoea or vomiting,
also cause volume depletion and may precipitate acute kidney injury (AKI).
NSAIDs, even in short courses, can cause AKI as a result of renal underperfusion.
Angiotensin-converting enzyme (ACE) inhibitors can also cause a deterioration in renal
function. However, this is a problem only in patients with compromised renal perfusion,
particularly those with renal artery stenosis.
Care should be taken when an ACE inhibitor and NSAID are prescribed together, as this
combination may precipitate an acute deterioration in renal function.

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Drugs causing intr arenal damage

Intrarenal damage may result in a direct toxic effect on the kidneys or hypersensitivity
reactions.
Most drugs that cause damage within the kidneys do so as a result of hypersensitivity
reactions, which involve either glomerular or interstitial damage.
 Drugs that have been reported to cause glomerulonephritis include penicillamine, gold,
captopril, phenytoin and some antibiotics, including penicillins, sulfonamides and
rifampicin.
Drugs that may cause interstitial nephritis include penicillins, cephalosporins,
sulfonamides, thiazide diuretics, furosemide, NSAIDs and rifampicin.
There are a number of drugs that cause direct toxicity to the renal tubules (acute tubular
necrosis) - eg, aminoglycosides, amphotericin and ciclosporin.

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Drugs causing postrenal damage (urinary tr act obstruction)

High-dose sulfonamides, acetazolamide or methotrexate may cause crystalluria and

could therefore cause urinary tract obstruction.
Anticholinergics (eg, tricyclic antidepressants), and alcohol may cause urinary tract
obstruction due to retention of urine in the bladder.

Related articles

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More related content

Other nephrotoxic drugs

Cephalosporins: cephaloridine, one of the first cephalosporins introduced, has been

associated with direct renal toxicity and is no longer in clinical use. Other cephalosporins
are much less likely to produce renal damage but third-generation cephalosporins (eg,
cefixime) have (very rarely) been reported to cause nephrotoxicity.
Analgesics:
 NSAIDs may cause AKI due to hypoperfusion and interstitial nephritis, as well as
analgesic nephropathy (chronic interstitial nephritis and papillary necrosis).
Analgesic nephropathy has been most commonly seen with combination analgesic
products that contain aspirin and/or paracetamol.
Analgesic nephropathy is one of the few preventable causes of CKD. Discontinuation
of the drugs often results in stabilisation or even improvement in renal function but
continued use leads to further renal damage.
Lithium: serum levels of lithium consistently above the therapeutic range have been
associated with development of a nephrogenic diabetes insipidus.

Use of a dosage table

Dose recommendations are based on the severity of renal impairment and creatinine
clearance and/or GFR. The serum creatinine concentration is sometimes used instead as a
measure of renal function but is only a rough guide, even when corrected for age, weight and
sex. Nomograms should be used where accuracy is important.

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Further reading & references

Peritoneal dialysis in chronic kidney disease; Renal Association (2010)
Chronic kidney disease: early identification and management of chronic kidney disease
in adults in primary and secondary care; NICE Clinical Guidelines (July 2014)

1. Bell JS, Blacker N, Leblanc VT, et al; Prescribing for older people with chronic renal
impairment. Aust Fam Physician. 2013 Jan-Feb;42(1-2):24-8.
2. Jones SA, Bhandari S; The prevalence of potentially inappropriate medication prescribing
in elderly patients with chronic kidney disease. Postgrad Med J. 2013 Feb 16.
3. Joosten H, Drion I, Boogerd KJ, et al; Optimising drug prescribing and dispensing in
subjects at risk for drug errors due to renal impairment: improving drug safety in
primary healthcare by low eGFR alerts. BMJ Open. 2013 Jan 24;3(1). pii: e002068. doi:
10.1136/bmjopen-2012-002068. Print 2013.
4. Erler A, Beyer M, Petersen JJ, et al; How to improve drug dosing for patients with renal
impairment in primary care - a cluster-randomized controlled trial. BMC Fam Pract. 2012
Sep 6;13:91. doi: 10.1186/1471-2296-13-91.
5. Continuing good CKD management; The Renal Association

Disclaimer: This article is for information only and should not be used for the diagnosis or
treatment of medical conditions. EMIS has used all reasonable care in compiling the
information but make no warranty as to its accuracy. Consult a doctor or other health care
professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author: Current Version: Peer Reviewer:

Dr Colin Tidy Dr Gurvinder Rull Dr Adrian Bonsall
Document ID: Last Checked: Next Review:
489 (v7) 23/09/2016 22/09/2021

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