30
VOLUME 7 NUMBER 1 • MARCH 2010
dehydration.
Patients in stage 3B, 4 and 5 CKD are likely to need dosage adjustments
and, as a result of this, will need ongoing monitoring. Some diagnostic
procedures such as an intravenous pyelogram and some computed tomo-
graphic scans require the use of contrast dye, which can be nephrotoxic. It
is important to alert the radiology department if renal disease is known or
suspected and the department will need an up-to-date eGFR result.
The eGFR is normalised for a person with a body surface area of 1.73
m
2
but this will need to be converted back to a non-normalised GFR in
people whose size differs significantly from average.
4,5
This is also particu-
larly important when prescribing in cancer chemotherapy. You can convert
a normalised eGFR to an actual eGFR using the Monstellar formula to
calculate a person’s body surface area (the square root of their height in
cm multiplied by their weight in kg, divided by 3 600).
4,6
Whenever possible, potentially nephrotoxic drugs should be avoided al-
together. Patients need to know about the potential dangers from nephro-
toxic non-prescription medicines and alternative remedies. These include
over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs),
Chinese herbal medicines, alternative therapies and other herbal treat-
ments.
7
Where there is doubt, refer to the summary of product characteristics
(SPC) and the BNF, which has a section on renal impairment and a table of
drugs to be avoided or used with caution in renal impairment. This means
starting with a lower dose of the drug, increasing the dose more gradu-
ally and monitoring renal function more frequently. It is wise to repeat the
eGFR within two weeks of starting treatment.
8
Lengthening the dosing interval has a lower risk of toxicity but a higher
risk of sub-therapeutic drug levels, whereas dose reduction offers a more
constant drug level but a higher risk of toxicity.
3
Patients with CKD require dosing adjustments for digoxin, some an-
tihypertensive agents, hypoglycaemic agents, anti-anaphylactic medica-
tion, antimicrobial agents, analgesic agents, NSAIDs and herbal products.
Many of these patients will require several of these types of agents during
the course of their disease.
The Drug and Therapeutics Bulletin reviewed drugs and the kidney in
2006
4
and the following section summarises some of its recommenda-
tions.
Antihypertensive drugs
Thiazide diuretics and ACE inhibitors are recommended as first-line treat-
ment for hypertension.
9
The trouble with diuretics is that as the eGFR falls,
less of the drug reaches the nephron, so the diuretic may lose its effec-
tiveness. When the GFR falls below 30 ml/min/1.73 m
2
or blood pressure
control deteriorates, thiazide diuretics may need to be replaced by more
potent loop diuretics such as furosemide.
10
Angiotensin II (Ang II) causes systemic vasoconstriction, which increas-
es blood pressure and kidney diffusion. It also causes vasoconstriction
of the efferent arteriole, increasing intraglomerular hydrostatic pressure.
Angiotensin receptor blocker (ARB) drugs inhibit the Ang II receptors and
ACE inhibitors act to inhibit the production of Ang II. The reduction in hy-
drostatic pressure results in a reduction in proteinuria and slowing of the
progression of kidney disease.
11
ACE inhibitors and ARBs are both, therefore, reno-protective. However,
when using these drugs, serum creatinine elevations will occur. An in-
crease of no more than 30% is acceptable after starting one of these
drugs as long as the creatinine level does not continue to rise.
12
During
initiation of ACE inhibitors or ARBs, it is recommended that serum creati-
nine or eGFR is monitored within one to two weeks of initiation.
Potassium levels should also be monitored. ACE inhibitors and ARBs
should not routinely be initiated in patients with a serum potassium higher-
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Hands On
Clinical recommendations on drug use for
patients with CKD
A medicines review should be undertaken in any newly identified
•
patient with CKD.
Patients with CKD should be asked about over-the-counter and
•
herbal medicines, to ensure medications are indicated and safe
for the individual to take.
Where a drug to be used “with caution” is prescribed in CKD, a
•
clinical review should take place every two weeks.
Greater care is required when initiating drugs in CKD stages 3B,
•
4 and 5.
Medications with toxic metabolites should be avoided. The least
•
nephrotoxic agents should be used, and alternative medications
prescribed if necessary to avoid potential drug interactions.
Clinicians should be aware of drugs with active metabolites that
•
can exaggerate pharmacological effects.
In patients with impairment of renal function, dosages of drugs
•
cleared by the kidney should be adjusted based on renal function
(calculated as creatinine clearance or GFR).
Initial dosages should be determined using published guidelines
•
where available and adjusted based on patient response.
Serum drug concentrations may be used to monitor effectiveness
•
and toxicity if appropriate.
Adapted from Munar
et al
. 2007
3
