Urinary heparan sulfate proteoglycan excretion in black African women with pre-eclampsia

Abstract

Background. The heparan sulfate proteoglycan of the glomerular basement membrane is considered to be mainly responsible for the charge selectivity of the glomerular basement membrane. Decreased heparan sulfate proteoglycan results in a decreased anionic charge of the glomerular basement membrane with increased heparan sulfate proteoglycan in the urine, and is believed to be responsible for the proteinuria in pre-eclampsia. Aim. To determine the urinary heparan and chondroitin sulfate proteoglycan levels in women with pre-eclampsia. Materials and methods. Eighty-four patients were studied: 28 were normotensive pregnant, 28 were nonproteinuric hypertensive, and 28 were pre-eclamptic. Urine samples were obtained and urinary glycosaminoglycan concentrations were determined using the dimethyl-methylene blue assay. Plotting absorbance against the concentrations of heparan and chondroitin sulfate proteoglycans drew a standard curve. The concentration of heparan and chondroitin sulfate proteoglycans was read-off from the linear portion of the standard curve. The standard solutions contained 25, 50, 100 and 200 mg/l heparan or chondroitin sulfate. The Mann–Whitney U-test was used to detect differences between the three groups, and the Pearson's correlation coefficient was calculated for clinical data correlation of the pre-eclamptic group. Results. Urinary excretion of heparan sulfate proteoglycan (123.1 ± 22.1 mg/l) was significantly increased in the pre-eclamptic group compared with the normotensive pregnant group (60.5 ± 5.1 mg/l; p < 0.0001) and the hypertensive nonproteinuric group (63. 2 ± 3.7 mg/l; p < 0.0001). Urinary chondroitin sulfate proteoglycan excretion followed a similar pattern, being significantly increased in the pre-eclamptic group (88.86 ± 9.79 mg/l) compared with the normotensive pregnant group (49.1 ± 8.49 mg/l; p < 0.0001) and the hypertensive nonproteinuric group (43. 9 ± 5.7 mg/l; p < 0.0001). A significant Pearson's correlation between 24-h urine output vs. 24-h protein excretion (r = 0.51; p < 0.001), and between loss of HSPG versus 24-h urinary protein excretion (r = 0.72; p < 0.0001) was obtained in the pre-eclamptic group. Conclusion. This study demonstrates a reduction of glomerular charge in pre-eclampsia. The strong correlation between the severity of proteinuria and the loss of charge supports the hypothesis that the loss of glomerular charge induces structural changes of the filtration barrier, and may be the mechanism responsible for the proteinuria in pre-eclampsia. Furthermore, the elevated levels of urinary proteoglycan (heparan and chondroitin sulfate proteoglycans) in this disorder show a loss into the urine rather than a neutralization of these macromolecules.