7. Drug-Induced Kidney Injury

Acute kidney injury is an independent risk factor for patient mortality, even with small decrements in kidney function. In addition, it increases length of stay in the hospital and increases cost of treatment. Renal injury is often multifactorial, with drugs being only one of the factors in its pathogenesis. Hence, it is often difficult to estimate involvement of drugs as a cause of acute kidney injury. However, some data shows that in almost one quarter of cases of severe acute kidney injury nephrotoxic drugs are signifficant contributors. Renal handling of drugs involves glomerular filtration, excretion through transcellular transport into tubular fluid and reabsorbtion from the tubular fluid. High renal blood flow and process of concentration of drugs and their metabolites during formation of urine predisposes kidneys to toxic drug injury. From the pathogenic (pathophysiologic) perspective drug-induced kidney injury can be devided into hemodynamic, intrinsic (injury to renal tissue) and intrarenal obstruction (obstruction of tubule fluid flow). From didactical point of view kidney histology can be divided into four compartments: glomeruli, tubules, interstitium and vasculature. Each of these compartments can be target of drug-induced injury, with clinical and laboratory manifestations being dependent on which of them is predominantly involved. It is important to appreciate that a single drug renal toxicity can involve multiple pathophysiologic pathways and that predisposing factors are common to virtually all causative agents mediating kidney injury. Dehydration, hypotension, preexisting kidney disease, advanced age, diabetes and simultaneous use of multiple nephrotoxic drugs all greatly increase risk for any nephrotoxic drug to exert its nephrotoxic effect. At an increased risk are particularly patients in intensive care units.