Glomerular changes in normo- and microalbuminuric patients with long-standing insulin-dependent diabetes mellitus.
Normalbuminuric patients who have long-standing IDDM have a wide range of renal structure, from within normal limits to advanced lesions that overlap those of patients who have high levels of MA and border on those seen in patients who have overt DN. Patients who have low-level MA have reduced glomerular structure similar to that of patients who have NA. Low GFR, hypertension, or both can occur in patients who have NA or low-level MA and are associated with more advanced lesions. Patients who have MA and AER greater than 45 mg/24 hr have more advanced lesions than do patients with NA or low-level MA, but similar lesions are present in these patients whether AER is greater than or less than 100 mg/24 hr. Increasing AER in NA and MA patients who have long-standing IDDM is associated with GBM and mesangial expansion. A structural basis for MA cannot currently be deduced from studies of glomerular epithelial cell fine structure, capillary wall charge site analysis, or immunohistochemical studies of renal ECM composition. Hemodynamic adaptations to mesangial expansion and reduced filtration surface and, perhaps, hydraulic conductivity may accelerate glomerular damage, as expressed by increasing AER. Microalbuminuria derives its clinical utility in IDDM, as it identifies a population of patients at statistically increased risk of progression to overt DN by acting as a marker of already well-established DN lesions. Although MA is currently the best of the widely used indicators of DN risk, it is not precise. Therapies that reduce MA may ultimately slow or prevent progression toward ESRD, but this finding requires confirmation by demonstrating that a given treatment strategy can preserve GFR.
Fioretto
P
P
Department of Internal Medicine, University of Padova, Italy.
Mauer
M
M
D000419:Albuminuria / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*