Clinically important drug nephrotoxicity results from the complex interplay between the intrinsic toxic capacity of the drug, the level of drug exposure, i.e. dosage and duration, and patient-related risk factors.
PREVENTION OF RENAL ADVERSE DRUG
REACTIONS
Clinically
important drug nephrotoxicity results from the complex interplay between the
intrinsic toxic capacity of the drug, the level of drug exposure, i.e. dosage
and duration, and patient-related risk factors.
Drugs
with a high nephrotoxic potential should be preserved for the treatment of
life-threatening diseases. The use of aminoglycoside antibiotics, for example,
should be limited to the treatment of sepsis or neutropenic fever. Cyclosporine
is part of the stan-dard immunosuppressive therapy after organ
trans-plantation, but its use in the treatment of psoriasis is more
questionable in view of the high incidence of chronic irreversible renal damage
(Vercauteren et al., 1998).
Many
toxic insults to the kidney, with the obvious exception of idiosyncratic drug
reactions, are related to the degree of exposure. Especially, in drugs that
accumulate in renal tissue prolonged or repetitive ther-apy is associated with
an accrued risk for toxicity. For example, aminoglycoside nephrotoxicity
occurred more frequently when therapy was prolonged for three or more days
(Pateson, Robson and Wagener, 1998). Drug interactions interfering with drug dispo-sition
may lead to nephrotoxicity. Inhibition of drug-metabolising enzymes or efflux
transporters decreases the rate of metabolism of the object drug. This, in
turn, can result in increased serum concentrations and potential drug toxicity
if the drug has a narrow therapeutic index. For instance, a major dose-related
adverse effect of statins is myopathy. If not recog-nised, rabdomyolysis and
ARF may result. The risk for ARF is significantly increased when statins are
combined with drugs inhibiting the CYP3A4 system such as cyclosporine,
macrolide antibiotics or itra-conazole (Vlahakos et al., 2002).
Age
along with pre-existing renal disease and volume depletion (i.e. true
hypovolaemia or reduced effective circulating volume) are well-recognised risk
factors for hospital-acquired ARF (Shusterman et al., 1987). The latter risk factor for nephrotoxicity is
modifiable by intervention prior to the exposure to a nephrotoxic insult. In
the case of radiocontrast-induced nephropathy, hydration with sodium chloride
or sodium bicarbonate (Merten et al.,
2004) before contrast exposure has been shown to protect against nephropathy.
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