Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats.
Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P < 0.01) but failed to increase in DI-DM. Urinary albumin excretion more than doubled in LE-DM but rose by only 34% in DI-DM rats (P < 0.05). Kidney hypertrophy was also less intense in DI-DM than in LE-DM (P < 0.001). These results suggest that VP plays a critical role in diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.
Bardoux
P
P
Institut National de la Santé et de la Recherche Médicale, Unité 367, 17, Rue du Fer à Moulin 75005 Paris, France.
Martin
H
H
Ahloulay
M
M
Schmitt
F
F
Bouby
N
N
Trinh-Trang-Tan
M M
MM
Bankir
L
L
D000419:Albuminuria; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D003919:Diabetes Insipidus / Q000235:genetics / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D006029:Glycosuria; D006984:Hypertrophy; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy; D009929:Organ Size; D051381:Rats; D011910:Rats, Brattleboro; D020318:Rats, Long-Evans; D014667:Vasopressins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D014667:Vasopressins; D003404:Creatinine