VOLUME 7 NUMBER 1 • MARCH 2010
29
SA JOURNAL OF DIABETES & VASCULAR DISEASE
C
hronic kidney disease (CKD) affects renal drug elimination and other important processes
involved in drug disposition, including absorption, drug distribution and non-renal clearance.
As a result, the reduced renal excretion of a drug or its metabolites can cause toxicity and
the sensitivity to some drugs is increased even if elimination is unimpaired.
Patients with renal impairment, particularly when eld-
erly, tolerate drug side-effects less well and, impor-
tantly, some drugs are not effective when renal func-
tion is reduced. The British National Formulary (BNF)
provides some important principles of dose adjust-
ment in renal impairment.
1
The level of renal function below which the dose of
a drug must be reduced depends on the proportion
of the drug eliminated by renal excretion or its toxic-
ity. Not all drugs are toxic and in this case precision
in dosing is less important. However, for more toxic
drugs, which may have a small safety margin, dose
regimens based on glomerular filtration rate (GFR)
should be used.
When initiating drug treatment in patients with
chronic kidney disease (CKD) stage 3A, caution and
careful thought are needed rather than dose adjust-
ment, but greater care is needed in CKD stages 3B,
4 and 5.
There are situations where both efficacy and toxic-
ity are closely related to plasma drug concentration.
In these situations, careful observation is necessary
and subsequent doses should be adjusted according
to clinical response and plasma drug concentration,
where measurement is possible. Other important fac-
tors that need to be taken into consideration include
dehydration, pre-existing heart failure and concomi-
tant drug therapy.
2
On the whole, loading doses do not usually need to
be adjusted in patients with chronic kidney disease
and dose adjustments can be made by reducing the
Prescribing for patients with
chronic kidney disease
Hands On
Michael Kirby
Visiting Professor, Faculty of Health
and Human Sciences, Centre for
Research in Primary and Community
Care (CRIPACC), and the Clinical Trials
Coordinating Centre, University of
Hertfordshire, Hatfield, UK.
maintenance dose of the drug, less frequent dosing
intervals or both.
Information in the BNF1 is based on creatinine clear-
ance, because published information on the effects of
renal impairment or drug elimination is usually given
in terms of creatinine clearance as a surrogate of GFR.
However, serum creatinine concentration is unreliable
and the creatinine clearance test is now rarely used,
having been replaced by the estimated GFR (eGFR).
The two measures of renal function are not inter-
changeable but, in practice, eGFR can be used to
determine dosage adjustments in place of creatinine
clearance for most drugs and for most patients of av-
erage build and height. However, for potentially toxic
drugs with a small safety margin and for patients who
are very under- or overweight, the absolute GFR should
be used. This is calculated by multiplying the eGFR by
the individual patient’s body surface area/1.73.
Patients in stage 1, 2 or 3A CKD will not usually
require dosage adjustments, but they are at risk of
continuing renal damage from disease progression,
adverse drug reactions, or both. Many of these pa-
tients will have concurrent conditions such as diabe-
tes, hypertension, and vascular disease. Ageing will
complicate the situation further.
Patients who have a family history of renal disease
or who are taking nephrotoxic drugs are also at in-
creased risk of progression. It is important to watch
out for the adverse effects of medication and be aware
of the patient’s fluid volume status, which includes
both fluid retention or excessive diuresis leading to
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