ADMINISTRATION OF DEXAMETHASONE INDUCES PROTEINURIA OF GLOMERULAR ORIGIN IN MICE

The administration of glucocorticoids has been reported to exacerbate proteinuria in a few patients with glomerulonephritis. This effect has not been well recognized, and the pathogenetic mechanism responsible for this phenomenon remains to be clarified. In this study, we observe d that a high daily oral dose (0.5 mg/kg body weight) of dexamethasone was capable of inducing overt proteinuria in mice, beginning on day 5 and persisting for a 19-day duration, One fourth of mice also intermi ttently presented with slight hematuria beginning on day 12, Renal les ions in the dexamethasone-treated mice, which were killed an day 23, w ere characterized by mild mesangial expansion, segmental or global hya linosis/sclerosis in deep cortical glomeruli, and focal tubular change s. No glomerular inflammatory cell infiltration or proliferative lesio n was noted in any of the mice. Ultrastructural features of glomeruli included mesangial widening characterized by either an increase of mes angial matrix, dilated mesangial channels filled with slightly electro n-dense material or mesangial lysis-like appearance showing intracytop lasmic microcysts filled with electron-lucent material, and evidence t o support injury of endothelial cells, erythrocytes, and podocytes. An immunofluorescence study revealed enhanced glomerular deposition of I gG, IgA, IgM, and fibrinogen (P < 0.001, compared with normal control mice), but no glomerular C3 deposition was identified in any of the de xamethasone-treated mice. Charge analysis showed no impairment in anio nic property of glomerular tufts in the dexamethasone-treated mice. In addition, the dexamethasone-induced proteinuria was greatly attenuate d by treatment with a low molecular weight heparin, although it was no t reduced by an angiotensin-converting enzyme Inhibitor, Data from the se experiments suggest that a large dose of glucocorticoids is potenti ally nephrotoxic. Alteration of a size-dependent permeability may pred ominantly contribute to the dexamethasone-induced proteinuria. However , the effect of glomerular hyperfiltration may be only partially invol ved in the pathogenesis of this dexamethasone-induced glomerulopathy i n mice. (C) 1998 by the National Kidney Foundation, Inc.