Albumin permeability in isolated glomeruli in incipient experimental diabetes mellitus.
OBJECTIVE
The pre-clinical phase of diabetic nephropathy is characterised by increased glomerular filtration rate and episodes of microalbuminuria. The cause of the microalbuminuria has been variably ascribed to alterations 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 very 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 insulin 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 glomerular area. Subsequently, albumin permeability, proteinuria, and iopamidol clearance were determined in an additional group of 40 diabetic animals studied at 24, 72, 96, and 120 h after induction.


RESULTS
Albumin permeability increased steadily from induction in streptozotocin-treated animals, reaching a plateau at approximately 120 h. Glomerular filtration rate was shown to increase significantly at approximately 7 days 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 appearance of the permeability defect in isolated glomeruli and inhibited the increase in glomerular filtration in intact animals. It did not prevent glomerular hypertrophy.


CONCLUSIONS
An albumin permeability defect exists early in isolated non-perfused glomeruli from streptozotocin-treated rats and seems to be independent of glomerular filtration rate alterations.
Carraro
M
M
Institute of Clinical Medicine, University of Trieste, Italy.
Mancini
W
W
Artero
M
M
Zennaro
C
C
Faccini
L
L
Candido
R
R
Armini
L
L
Calci
M
M
Carretta
R
R
Fabris
B
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D006943:Hyperglycemia / Q000503:physiopathology; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use; D007479:Iopamidol / Q000493:pharmacokinetics; D007678:Kidney Glomerulus / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D010539:Permeability; D011507:Proteinuria; D051381:Rats; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012016:Reference Values; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*
D001786:Blood Glucose; D007328:Insulin; D012710:Serum Albumin, Bovine; D007479:Iopamidol