[Renal impairment induced by nonselective prostaglandin inhibitor]

The role of kidney function is of utmost importance in the maintenance of constant body fluid amount. However, kidneys are at a great risk of exposure due to high intrarenal blood flow and the existing concentrate system. Different damage can originate from renal clearance of various drugs, while metabolites or xenobiotics may be associated with potential nephrotoxic effects, particularly in the presence of additional risk factors. For analgesics such as nonsteroidal antirheumatics (NSARs), it is possible that they inhibit renal production of prostaglandins, potent vasodilators, resulting in tissue ischemia and direct toxicity. Therefore, the aim of this study was to evaluate changes in the cellular potential response of proximal tubules first in the presence of prostaglandin type E (PGE2) and then in the presence of Na-diclofenac, a nonselective prostaglandin inhibitor, and their effects on transport process of substrate (glucose), by using electrophysiological studies in experimental animals. PGE2 was found to play specific role at local intrarenal level, where they directly stimulated the processes of sodium and substrate (glucose) cotransport through luminal membrane of proximal tubules, without changing the control cell potential response. Results with diclofenac as a nonselective cyclooxygenase inhibitor and thus prostaglandin synthesis inhibitor revealed it to cause concentration-dependent depolarization of the cellular potential. It also reduces cotransport of the substrates and ions involved in intracellular equilibrium. At concentrations higher than therapeutic, diclofenac became nonspecific and therefore caused permanent depolarization. Accordingly, the results of these experimental studies may be useful to specialists treating patients suffering from renal dysfunction or kidney diseases. This can also contribute to rationalization of the therapeutic use of analgesics, greater caution and better recognition of the associated risk factors, in elderly or renal patients in particular.