Glucocorticoids and control of glomerular filtration rate

Glucocorticoids given acutely or chronically at physiological/pharmacological doses increase GFR in both experimental animals and humans. Glomerular micropuncture studies have shown that in the normal rat kidney, glucocorticoids vasodilate both the preglomerular and efferent resistances and result in an increase in glomerular plasma flow, which is the sole factor responsible for the increase in GFR. However, the mechanism(s) initiating these alterations in the glomerular microcirculation remain obscure. The glucocorticoid-induced increase in GFR does not appear to be due to volume expansion or alteration in tubulo-glomerular feedback activity. Chronic glucocorticoid administration has been shown to increase renal prostaglandin synthesis in some but not all species; however, a link between increased prostaglandin production and glucocorticoid-induced increase in GFR has not been established. A number of studies have examined glucocorticoid-induced alterations in renal vascular reactivity to vasoconstrictor agonists and the data have been conflicting. The suggestion that glucocorticoid-stimulated ANP production evokes the increase in GFR is unlikely to be correct based on substantial differences in the glomerular hemodynamic changes seen with ANP or glucocorticoids. An interesting proposal that appears well worth exploring is that glucocorticoids may increase GFR through their effects on catabolism of proteins to increase production of amino acids. Amino acid infusion markedly elevates GFR and has a similar glomerular hemodynamic profile as that of glucocorticoids. By virtue of their action to increase GFR, glucocorticoids increase the rate of electrolyte and water delivery into the nephron. Therefore, glucocorticoid-induced alterations in electrolyte and water excretion may be secondary to an elevation in GFR, in addition to direct actions of glucocorticoids on the tubule. Also, by determining the hemodynamic state of the kidney, and hence, rate of fluid delivery through the nephron, glucocorticoids may influence the sensitivity of the nephron to regulatory influences. Glucocorticoids have their most profound effect (especially clinically) by modifying the immunological or cellular mechanisms responsible for glomerular injury. Less important is their ability to increase GFR. In view of some evidence that suggests increasing glomerular pressure accelerates the progression of established renal disease, some might speculate that glucocorticoids actually increase glomerular damage under certain conditions.