Prevention of Renal Adverse Drug Reactions

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.