Glomerular permselectivity at the onset of nephropathy in type 2 diabetes mellitus.
The development of microalbuminuria in individuals with type 2 diabetes mellitus is associated with a 10-fold increase in the risk of progression to overt nephropathy and eventual end-stage renal failure. The present study reports long-term (up to 8 yr) follow-up of 43 Pima Indians with type 2 diabetes detected on screening to have microalbuminuria. The natural history of albuminuria in these individuals included progression to overt proteinuria (urinary albumin excretion > or = 300 mg/d) in half of the participants by 7 yr of follow-up. The size selectivity of the glomerular barrier was also investigated using dextran sieving and pore theory. Whereas a comparison group of macroalbuminuric Pima Indians had an excess of large pores that served as a macromolecular "shunt," individuals with microalbuminuria had a shunt size no different from long-term diabetic, normoalbuminuric control subjects. An abrupt transition from little or no relationship to a highly significant and positive relationship between increasing albuminuria and shunt size occurred at an albumin-to-creatinine ratio of approximately 3000 mg/g. Shunt size in macroalbuminuric individuals correlated with the extent of foot process broadening. Podocyte foot processes in microalbuminuric participants were not different from those in control subjects. In conclusion, although microalbuminuria in type 2 diabetic Pima Indians often heralds progressive glomerular injury, it is not the result of defects in the size permselectivity of the glomerular barrier but rather of changes in either glomerular charge selectivity or tubular handling of filtered proteins or of a combination of these two factors.
Lemley
Kevin V
KV
Division of Pediatric Nephrology, Stanford University School of Medicine, Stanford, California.|Division of Nephrology, Stanford University School of Medicine, Stanford, California.
Blouch
Kristina
K
Division of Nephrology, Stanford University School of Medicine, Stanford, California.
Abdullah
Isha
I
Division of Nephrology, Stanford University School of Medicine, Stanford, California.
Boothroyd
Derek B
DB
Department of Statistics, Stanford University School of Medicine, Stanford, California.
Bennett
Peter H
PH
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Phoenix, Arizona.
Myers
Bryan D
BD
Division of Nephrology, Stanford University School of Medicine, Stanford, California.
Nelson
Robert G
RG
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Phoenix, Arizona.
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000378:metabolism* / Q000652:urine; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000378:metabolism*; D018450:Disease Progression; D005919:Glomerular Filtration Rate; D006801:Humans; D007198:Indians, North American; D007678:Kidney Glomerulus / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D010539:Permeability; D011507:Proteinuria / Q000652:urine; D012016:Reference Values