Long-term furosemide treatment in the normal rat: dissociation of glomerular hypertrophy and glomerulosclerosis.

Abstract

Furosemide treatment produces glomerular hypertrophy and augments glomerular capillary hydraulic pressure in the normal rat. Similar processes have been implicated in the progression of glomerulosclerosis (GS). Whereas prior experiments with furosemide treatment of 6 to 8 weeks duration have produced no detrimental effects on renal function or structure, the effects of more prolonged treatment are unknown. Male Munich-Wistar rats were pair fed with or without furosemide, 40 mg/d, from the time of weaning through 10 months of age. At selected time points, 24-hour urine collections were obtained for total protein and volume determination. At the end of the study, light and electron microscopic morphometric studies were performed. Renal cortical hypertrophy and glomerular hypertrophy were sustained throughout the 9 months of treatment in the group receiving furosemide. The cortical interstitial area was increased in the furosemide group, but this did not appear to be the result of fibrosis. Proximal and distal tubule diameter were unaffected by treatment. No differences in GS or glomerular ultrastructure were shown. This study provides no evidence of detrimental glomerular effects of furosemide in normal animals. Further studies of furosemide treatment under conditions of preexisting renal pathological conditions are warranted to confirm the safety of this treatment in situations analogous to those seen in the clinical setting. Interstitial expansion also warrants further study in this setting.