Novel aspects of pharmacological therapies for acute renal failure.
Acute renal failure (ARF) comprises several syndromes that are associated with a sudden decrease in renal function. ARF is common among critically ill patients, is typically multifactorial and is of great prognostic significance. Indeed, even moderate changes in renal function significantly add to the morbidity and worsen mortality associated with ARF. Recent definitions, namely the renal Risk, Injury, Failure, Loss of renal function and End-stage kidney disease (RIFLE) classification or Acute Kidney Injury Network (AKIN) criteria, which incorporate the levels of oliguria in addition to fractional serum creatinine elevation, are important because the magnitude of kidney injury according to those definitions correlates very well with both short- and long-term patient survival. However, preventive strategies are most effective when started before oliguria or elevated serum creatinine is detectable, as those criteria already reflect established renal tubular cell injury. New biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP) or kidney injury molecule-1 (KIM-1) that increase prior to the serum creatinine elevation are promising and have been proven to be useful in this regard in a few clinical trials. In addition, genetic profiling may define patients at risk earlier and help to individualize preventive strategies. Well established strategies include limiting dehydration and hypotension by the use of intravenous isotonic fluids at an optimal and individualized rate, as well as avoiding exposure to nephrotoxins, which include aminoglycosides, amphotericin or non-ionic contrast. Generally accepted and evidence-based pharmacological preventive or therapeutic options have not yet been established, although many drugs (e.g. renal vasodilators, diuretics and HMG-CoA reductase inhibitors [statins]) have been tested. New promising agents interfere with the apoptotic signalling that can occur in the setting of toxin exposure or ischaemia-reperfusion injury, limit inflammatory responses or modulate endothelial cell activation. In the future, these new approaches will enable us to extend our therapeutic repertoire.
Division of Nephrology and Hypertension, University of Kiel, Kiel, Germany. kunzendorf@nephro.uni-kiel.de
Ulrich
U
Kunzendorf
Michael
M
Haase
Lars
L
Rölver
Anja
A
Haase-Fielitz
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors
D015415:Biomarkers; D003404:Creatinine