This study examined whether the prevention of diabetes-related albuminuria by aminoguanidine (AG) or ramipril (RAM) may be mediated by a common postglomerular basement membrane renal intracellular mechanism involving protein kinase C (PKC). The renal handling of albumin was examined over 24 weeks in control and streptozotocin (STZ)-induced diabetic rats. A radioimmunoassay (RIA) that measures intact albumin, and intravenously injected tritium-labeled rat serum albumin, was used to assess the proportion of intact albumin and albumin fragments in urine. Diabetes was induced in male Sprague-Dawley rats by the intravenous administration of STZ at a dose of 5 0 mg/kg. Age-matched control rats received buff e r alone. Diabetes was characterized by an increase in blood glucose (>15 mmol/l), an increase in GHb (means at 24 weeks 29.3 ± 1.1%; control 6.1 ± 0.1%, P < 0.005), an increase in glomerular filtration rate (GFR) (4.13 ± 0 . 1 5 ml/min; control 3.54 ± 0.19 ml/min, P < 0.005), an increase in intact albumin excretion rate (expressed as geometric mean 11.64 / 2 . 1 1 mg/24 h; control 0.74 / 1 . 5 7 mg/24 h, P < 0.

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Further studies are required to define the safety of the formulation of irinotecan with HA. While this study was not adequately powered to demonstrate survival differences, these phase II data indicated HA-Irinotecan to be a promising therapy demonstrating improved efficacy compared to irinotecan-alone.