Albumin permeability in isolated glomeruli in incipient experimental diabetes mellitus

Aims/hypothesis. The pre-clinical phase of diabetic nephropathy is characte rised by increased glomerular filtration rate and episodes of microalbuminu ria. The cause of the microalbuminuria has been variably ascribed to altera tions of the size or charge selective barriers of the glomerulus or both or as a consequence of the haemodynamic changes. Our aim was to investigate v ery early albumin permeability alterations in isolated glomeruli which were not subject to perfusion pressure. Methods. Isolated glomeruli were studied from 120 male Wistar rats, divided into three groups: streptozotocin-treated, streptozotocin-treated with ins ulin pellet implants, and controls. From each group ten animals were killed at 7, 14, 28, and 56 days after induction. Study variables included blood pressure, proteinuria, iopamidol clearance, albumin permeability and glomer ular area. Subsequently, albumin permeability, proteinuria, and iopamidol c learance were determined in an additional group of 40 diabetic animals stud ied at 24, 72, 96, and 120 h after induction. Results. Albumin permeability increased steadily from induction in streptoz otocin-treated animals, reaching a plateau at approximately 120 h. Glomerul ar filtration rate was shown to increase significantly at approximately 7 d ays and proteinuria correlated with it. Glomerular hypertrophy was observed both in streptozotocin-treated animals and in streptozotocin-treated rats with insulin pellet implants. Strict blood glucose control delayed the appe arance of the permeability defect in isolated glomeruli and inhibited the i ncrease in glomerular filtration in intact animals. It did not prevent glom erular hypertrophy. Conclusion/interpretation. An albumin permeability defect exists early in i solated non-perfused glomeruli from streptozotocin-treated rats and seems t o be independent of glomerular filtration rate alterations.