INHIBITION OF RENAL ORNITHINE DECARBOXYLASE ACTIVITY FAILS TO REDUCE KIDNEY SIZE AND URINARY ALBUMIN EXCRETION IN DIABETIC RATS WITH MANIFEST KIDNEY HYPERTROPHY

Formation of polyamines has previously been shown to play an important role for initial kidney growth in experimental diabetes, as treatment of diabetic rats with a selective ornithine decarboxylase (ODC) inhib itor, initiated immediately after diabetes induction, abolishes the in itial kidney growth. In order to investigate the role of polyamine for mation for the maintenance of diabetic kidney hypertrophy, ODC inhibit ion was initiated after manifest kidney hypertrophy had occurred. The kidney weight in diabetic rats was significantly larger than in contro l rats after a diabetes duration of 7, 14, 50 and 71 days and the tota l glomerular volume was increased in kidneys from diabetic rats after a diabetes duration of 71 days. Renal activity of ODC was increased in diabetic rats throughout the study period of 71 days. Treatment of di abetic rats with the selective ODC inhibitor di-fluoro-methyl-ornithin e (DFMO) was maintained for two periods (days 7-14 and days 50-71). DF MO treatment had no effect on 24-h food consumption, blood glucose con centration or body weight. However, despite almost total inhibition of the kidney ODC activity, there was no effect on kidney growth or tota l glomerular volume in the DFMO treated diabetic rats compared to plac ebo treated diabetic rats. Finally, the urinary albumin excretion was markedly increased in diabetic rats with no effects of ODC-inhibition. In conclusion, inhibition of ODC initiated in diabetic rats with mani fest kidney enlargement had no effect on renal size, glomerular volume or urinary albumin excretion. These findings together with our previo us findings indicate that the role of polyamines in diabetic kidney en largement is restricted to the first week after diabetes induction.