VOLUME 7 NUMBER 1 • MARCH 2010
31
than-the-normal reference range. Beware of volume depletion caused by
gastrointestinal upsets, particularly in the elderly on these drugs, as this
can cause acute renal failure. This will usually reverse within two or three
days of discontinuing the ACE inhibitor or ARB drug, which can be rein-
stated when recovery has taken place.
13
Propranolol, metoprolol and carvedilol are metabolised by the liver and
can be used at the usual doses. However, atenolol, bisoprolol, celiprolol,
nebivolol and sotalol may need reduction in the dose or frequency of dos-
ing. The calcium channel blockers amlodipine and nifedipine can be used
at the usual doses, but verapamil, diltiazem and lercanidipine may require
reduction in the dose or frequency. Lercanidipine is not recommended
when GFR is below 30 ml/min. Digoxin requires a 25–75% dosage reduc-
tion when the GFR falls below 50 ml/min
14
and levels should be checked
regularly.
Antiepileptic drugs
In the early stages of renal disease, phenytoin can be used at the usual
dose, but once kidney disease becomes severe, protein binding is af-
fected, with greater distribution of the drug to other tissues.
15
The dose
may need to be reduced for gabapentin, pregabalin, sodium valproate and
vigabatrin. Carbamazepine requires very close monitoring and a critical
benefit/risk appraisal.
Antidepressant drugs
Citalopram and fluoxetine can be used at usual doses in mild/moderate
CKD but the dose may need to be reduced with paroxetine and venlafax-
ine. Beware of lithium toxicity.
Analgesics and NSAIDs
These drugs are linked to a three-fold increased risk of acute renal failure.
Their use can cause nephrotic syndrome with interstitial nephritis, and re-
sult in chronic kidney disease. Short-term NSAID use can be well tolerated
if the patient is well hydrated and has good renal function in the absence
of heart failure, diabetes or hypertension.
3
However, these drugs inhibit
cyclo-oxygenase (COX) enzymes, causing altered renal blood flow and
reduction in GFR.
16
They can also cause salt and water retention, together
with hypertension, and may cause interstitial nephritis.
17
Patients with renal artery stenosis, cardiac failure and liver disease are
more vulnerable, particularly if they become dehydrated.
18
As with ACE
inhibitors, NSAIDs should be stopped immediately whenever there is de-
hydration or fluid depletion. Particular care should be taken when using
NSAIDs with diuretics and/or ACE inhibitors.
19,20
COX-2 inhibitors should
also be avoided in renal disease, wherever possible.
21
Aspirin use in CKD
should be restricted to its cardiovascular indications.
1
Alternatives to NSAIDs include paracetamol, which can be used at the
usual dose, although this should be used with caution. Due to increased
sensitivity, all opioid analgesics should be given at a reduced dose and/
or increased dosage interval. Codeine, dihydrocodeine, morphine and tra-
madol doses must be reduced because of reduced excretion of both the
drugs and their active metabolites. Fentanyl, hydromorphone and oxyco-
done do not appear to have active metabolites that require renal elimina-
tion and, therefore, may be preferred.
Antimicrobial drugs
Trimethoprim is secreted by the renal tubules and is, therefore, an effec-
tive agent for treating lower urinary tract infections. The dose needs to be
lowered in CKD and the patient monitored for hyperkalaemia and increas-
ing creatinine concentration.
Doxycycline, clarithromycin, erythromycin, fluconazole, ketoconazole,
metronidazole, co-fluampicil and amoxicillin can be used at normal doses.
Examples where things have gone wrong
Elderly lady with CKD (creatinine 220
•
μ
mol/l, but eGFR 30) on
furosemide/ACE-I for CCF who developed diarrhoea and became
dehydrated leading to acute renal failure and needed dialysis for
two weeks. Advice is to stop furosemide/ACE (and NSAIDs) during
any intercurrent illness associated with pyrexia or fluid loss (diar-
rhoea and vomiting).
Patient with CKD and UTI given trimethoprim – creatinine rises
•
from 200
μ
mol/l to 400
μ
mol/l (but comes down nicely within
seven days once it is stopped). Advice is to avoid trimethoprim
in CKD (use
eg
cephalosporin). This is not really renal failure so
much as interference with tubular creatinine excretion, but caused
considerable concern nonetheless – and was totally avoidable.
Patient with CKD develops shingles. Given normal dose aciclo-
•
vir and ends up with neurotoxicity (confusion, impaired conscious
level), suspected encephalitis but lumbar puncture (LP) normal.
Aciclovir was stopped, resulting in complete recovery. It is really
important that the acicolvir dose is reduced according to GFR.
Digoxin toxicity is rare because most people know to reduce the
•
dose of digoxin in CKD.
NSAID drugs: use only if absolutely necessary, as they are the
•
most frequent cause of acute or chronic renal failure. They should
be given for the shortest time with caution and with careful moni-
toring of blood tests, BP and fluid retention if a CKD patient needs
more than a week’s treatment. Should be avoided in everyone in
stage 4 CKD (simple analgesics preferred).
SA JOURNAL OF DIABETES & VASCULAR DISEASE
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