The Steno Hypothesis and Glomerular Basement Membrane Biochemistry in Diabetic Nephropathy

1994 ◽  
pp. 203-212 ◽  
Author(s):  
Allan Kofoed-Enevoldsen
Keyword(s):  
Diabetic Nephropathy ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Basement Membrane Biochemistry

Temporary effects of circulating Amadori products on glomerular filtration properties in the normal mouse

2001 ◽  
Vol 280 (1) ◽  
pp. F103-F111 ◽  
Author(s):  
I. Londoño ◽  
M. Bendayan
Keyword(s):  
Diabetic Nephropathy ◽  
Basement Membrane ◽  
Glomerular Filtration ◽  
Glomerular Basement Membrane ◽  
Normal Mouse ◽  
Early Diabetes ◽  
Amadori Products ◽  
Time Points ◽  
Glycated Proteins ◽  
Filtration Properties

Previous studies have established a preferential glomerular filtration of glycated BSA (gBSA), as well as a facilitated filtration of BSA in the presence of gBSA. We intend to determine whether these modifications are permanent or transitory. gBSA was intravenously injected into anesthetized normal mice and maintained in circulation for 30 min, 1, 2, 24, and 48 h. Five minutes before death, FITC-BSA was injected. On immunocytochemical evaluations, increased glomerular filtration of FITC-BSA was found at all circulating time points. Changes at 24 and 48 h were less pronounced. Glomerular basement membrane (GBM)-to-lumen gBSA labeling ratios were similar at all time points suggesting no accumulation of gBSA in the GBM. Seventy percent of the gBSA was cleared from the circulation and the GBM after 24 h, and 95% after 48 h. This was confirmed in experiments with radiolabeled tracers. These results suggest that the alteration in GBM permeability to BSA in the normal mouse are due to the presence of gBSA and are gradually overcome along with its clearance from circulation. In early diabetes, increasing concentrations of circulating glycated proteins could be responsible for changes in glomerular permselectivity and probably for the alteration in glomerular filtration properties leading to diabetic nephropathy.

scholarly journals Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy

Diabetologia ◽  
1995 ◽  
Vol 38 (10) ◽  
pp. 1169-1175 ◽  
Author(s):  
J. H. M. Berden ◽  
J. van den Born ◽  
A. A. van Kraats ◽  
M. A. H. Bakker ◽  
K. J. M. Assmann ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Heparan Sulphate ◽  
Anionic Sites

scholarly journals Danaparoid sodium lowers proteinuria in diabetic nephropathy.

1997 ◽  
Vol 8 (3) ◽  
pp. 456-462 ◽  
Author(s):  
J W van der Pijl ◽  
F J van der Woude ◽  
P H Geelhoed-Duijvestijn ◽  
M Frölich ◽  
F J van der Meer ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Side Effects ◽  
Basement Membrane ◽  
Renal Disease ◽  
Heparan Sulfate ◽  
Crossover Study ◽  
Glomerular Basement Membrane ◽  
Diabetic Patients ◽  
Danaparoid Sodium ◽  
Urinary Creatinine

Diabetic nephropathy is a progressive renal disease with thickening of the glomerular basement membrane and mesangial expansion and proliferation as histological hallmarks. The presence of the glycosaminoglycan side chains of heparan sulfate proteoglycan, an important constituent of the glomerular basement membrane, is decreased in diabetic nephropathy proportionally to the degree of proteinuria. Danaparoid sodium is a mixture of sulfated glycosaminoglycans consisting mainly of heparan sulfate. The study presented here involved performing a randomized placebo-controlled crossover study with danaparoid sodium in diabetic patients with overt proteinuria. The aim of the study was to evaluate the effect on proteinuria and safety/tolerability. Nine patients completed the study, without major side effects; the crossover study consisted of two 6-wk periods of treatment with 750 anti-Xa units danaparoid sodium subcutaneously once-daily or placebo. Following danaparoid sodium, significant declines of both albuminuria and proteinuria were found. After danaparoid sodium, the albumin excretion ratio standardized for urinary creatinine reduced with 17% in comparison with an increase of 23% after placebo (95% confidence interval of the difference,-75.9-3.9%; P = 0.03). The percentage change of the urinary protein excretion corrected for urinary creatinine differed at 8 wk significantly between both treatment arms (P = 0.001). Additional parameters for safety as hematological, hemostasis, biochemical parameters, and fundusphotography did not show any clinically significant difference for both groups. Only two patients had minor skin hematomas at the injection site while using danaparoid sodium. In conclusion, the supplementation was found to be feasible and was not associated with side effects. A significant decline of proteinuria was found. More prospective dose-finding and long-term studies must be performed to see whether danaparoid sodium could not only induce a reduction of proteinuria but also halt the progression of renal disease.

scholarly journals Selective proteinuria in diabetic nephropathy in the rat is associated with a relative decrease in glomerular basement membrane heparan sulphate

Diabetologia ◽  
1995 ◽  
Vol 38 (2) ◽  
pp. 161-172 ◽  
Author(s):  
J. van den Born ◽  
A. A. van Kraats ◽  
M. A. H. Bakker ◽  
K. J. M. Assmann ◽  
L. P. W. J. van den Heuvel ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Heparan Sulphate ◽  
Relative Decrease
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