CYP3A5 ALLELE A IS ASSOCIATED WITH HIGHER BLOOD PRESSURE VALUES IN YOUNG PATIENTS WITH KIDNEY TRANSPLANT ON CALCINEURIN INHIBITORS

The second part of this in-depth clinical review focuses on drugs used in the prevention of AKI in the patient at risk and/or in the management of the patient with incipient AKI. Among the drugs used to maintain a normal renal perfusion pressure, norepinephrine and vasopressin are most commonly used in hypotensive critically ill patients. The most recent RCT did not find a difference between low-dose vasopressin plus norepinephrine and norepinephrine alone in patients with septic shock, suggesting that either approach is reasonable. However, vasopressin may be beneficial in the less severe septic shock subgroup. Loop diuretics may convert an oliguric into a non-oliguric form of AKI that may allow easier fluid and/or nutritional support of the patient. Volume overload in AKI patients is common and diuretics may provide symptomatic benefit in that situation. However, loop diuretics are neither associated with improved survival, nor with better recovery of renal function in AKI. Among the renal vasodilating drugs, the routine administration of dopamine to patients for the prevention of AKI or incipient AKI is no longer justified. On the other hand, although additional studies may be warranted, fenoldopam may appear to be a likely candidate for the prevention of AKI, particularly in critically ill patients, if the positive results obtained in some recent studies are confirmed. Trials with natriuretic peptides were in general inconclusive but despite the fact that nesiritide is currently approved by the FDA only for the treatment of heart failure, this vasodilator may in the future play a role in the prevention of AKI, particularly in association with heart failure and cardiac surgery. The most recent trials seem to confirm a potential positive preventive effect of N-acetylcysteine (NAC), particularly in contrast-induced nephropathy (CIN), NAC alone should never take the place of IV hydration in patients at risk for CIN; fluids likely have a more substantiated benefit. At present, initiation of statin therapy for the prevention of CIN cannot be recommended, but these drugs should not be stopped before a radiological intervention in patients on chronic statin therapy. Rasburicase is very effective in the prevention of acute tumour lysis syndrome. Erythropoietin (EPO) has tissue-protective effects and prevents tissue damage during ischaemia and inflammation, and currently trials are performed with EPO in the prevention of AKI post-cardiac surgery, CIN and post-kidney transplantation. From this review it becomes clear that single-drug therapy will probably never be effective in the prevention of AKI and that multiple agents may be needed to improve outcomes. In addition, drugs should be administered early during the course of the disease.