Decreased glomerular basement membrane heparan sulfate proteoglycan in renal hypertension

Heparan sulfate proteoglycans (HS-PG) are major components of the glomerular basement membrane (GBM) and play a key role in their molecular organization and function. Moreover, their presence is essential for the maintenance of the selective permeability of the GBM. Recently, we have isolated and characterized a novel small basement-membrane associated HS-PG from human aorta and kidney. By the use of specific monoclonal antibodies we have shown that the novel HS-PG is predominantly located in the GBM. Turnover or, in the course of kidney diseases, degradation of HS-PG from the GBM may lead to urinary excretion of HS-PG. Recently we have shown, that HS-PG is strongly decreased in the GBM of patients with essential hypertension. The aim of the present study was to analyze, whether changes of structure and function of the GBM in patients with renal hypertension can also be detected by measuring the excretion of HS-PG into urine with a sensitive enzyme immunoassay. An standardized exercise protocol was developed which allows to determine the HS-PG content and to exclude the influence of de novo HS-PG synthesis. Before, 15 and 45 min after exercise biochemical characterization of the urinary proteins and HS-PG was performed. A hundred-fold increase in the urinary excretion of HS-PG was seen in normal subjects under exercise. In contrast, in patients with renal hypertension the HS-PG excretion was much less pronounced, leading to only a 2-5-fold increase. These findings were confirmed by immunohistochemical analysis of kidney biopsies using the HS-PG specific monoclonal antibody 1F10/B8. Taken together, these data strongly suggest that HS-PG is decreased in the GBM of patients with renal hypertension.