engleski

Changes in kidney function after glucocorticoid treatment

Introduction: Glucocorticoids are often used in many acute or chronic diseases to suppress corresponding symptoms. Short–term glucocorticoid treatment in clinical practice are used for supportive therapy with setrons (antiemetics) in premedication before providing chemotherapy with high emetogenic drugs, then, to reduce oedema at high intracranial pressure as well as for acute interstitial nephritis. However, the response inside the kidney to the short-term application of glucocorticoids is not yet well defined. Therefore, the aim of this study was to observe diuretic response to dexamethasone (the steroidal anti-inflammatory drug) and compare them to controls or to other group of drugs such as diclofenac and indomethacin (the non-steroidal anti-inflammatory drugs = NSAIDs). Materials and Methods: The experiments were performed on male Wistar rats. Cumulative urine volume was collected inside separate metabolic cages during 24 hours, and electrolyte analysis performed before and after intraperitonealy drug administration. Results: Results obtained with dexamethasone indicated stimulation of diuresis, i.e. urine volume increased in dose-dependent manner: 0.2 mg/kg b.m. by 43%, 0.4 mg/kg b.m. by 54% and 0.8 mg/kg b.m. by 63% after 24 hours in comparison to the control values (n=3-9). Time dependent stimulation in diuresis and sodium excretion was most pronounced within third and eight hours after drug application. Contrary to that, results obtained with the NSAID Na-diclofenac at a pharmacological dose (4 mg/kg b.m.) showed a diuresis decrease by 18.2 +/- 5.2% as early as at 24 h (n=12). The experiments performed with another NSAID such as indomethacin (2.8 mg/kg b.m.) also showed diuresis reduction by 12.0% +/-9% (n=5) at 24 h. Conclusions: An opposite diuretic response by short-term application of both group of drugs (steroidal and non-steroidal anti-inflammatory drugs) indicate that different mechanisms are involved. Study results showed that glucocorticoids such as dexamethasone influenced some processes involved in the regulation of tubular ion transport and/or by changing activity of some enzymes. Dexamethasone is possibly binding to the high affinity corticoid receptor, which is one of the nuclear receptors and change its transcriptional activity. By changing the activity of some enzymes (kinase isoforms), its change the activity of ion channels and Na, K-ATPase, which are involved in the regulation of transport processes and consequentially in the diuretic response. This short-term dexamthasone effect, makes them especially useful for therapy in conditions were water retention would be disadvantage. However, NSAIDs such as diclofenac and indomethacin led to an opposite effect, ed. caused diuresis reduction, what indicate that different mechanisms are involved. The effect of NSAIDs might be interpreted as a consequence of intrarenal vasoconstriction caused by diminished vasodilatatory prostaglandins and modulation of tubular ion transport processes. Therefore, therapeutic doses of NSAIDs can cause acute renal insufficiency as side effects, because of exposure to high intrarenal blood flow and drug concentration.

kidney; glucocorticoid

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