Background/Purpose: The heparin sulphate proteoglycans (HSPGs) in the glomerular basement membrane (GBM) play an important role in the charge-selective permeability of the glomerular filter. The b-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by selectively degrading the negatively charged side chains of HSPGs within the GBM in various forms of glomerulonephritis. We evaluated plasma and urinary activity of heparanase and determined association between its levels and proteinuria in patients with lupus nephritis.

Methods: Plasma from 86 patients with systemic lupus erythematosus (SLE) and 24 normal healthy subjects were collected. The clinical and laboratory data of the patients were obtained at the time of sampling. Forty six patients had a history of lupus nephritis and their urine was also collected. Proteinuria was defined as more than 500 mg/24h or spot urine protein/creatinine ratio > 0.5. Heparanase activity of plasma and urine was determined by a commercially available kit.

Results: Plasma heparanase activity was significantly elevated in SLE patients compared to healthy controls (734.9 ± 91.1 vs. 203.6 ± 87.1 mIU/ml, p = 0.038), but its activity was not different between patients with lupus nephritis and those without (743.3 ± 105.5 vs. 722.3 ± 166.1 mIU/ml, p = 0.915). However, urinary heparanase activity was significantly elevated in SLE patients with lupus nephritis compared to those without lupus nephritis and healthy controls (1299.7 ± 200.5 vs. 337.5 ± 35.2 and 203.6 ± 87.1 mIU/ml, p = 0.046 and 0.026, respectively). Thirty six of patients with lupus nephritis showed significant proteinuria and urinary heparanase activity of them was significantly elevated compared with those of patients without proteinuria (997.0 ± 245.3 vs. 194.6 ± 122.0 mIU/ml, p = 0.006). Importantly, urinary heparanase activity was positively correlated with protein excretion (r = 0.381, p = 0.003). Moreover, urinary heparanase activity showed an inverse correlation with C3 complement level and complement haemolytic activity (CH50) (r = -0.495, p = 0.002 and r = -0.565, p < 0.001) and had a tendency to associate negatively with C4 complement levels (r = -0.299, p = 0.072).

Conclusion: Urinary heparanase activity was elevated in patients with lupus nephritis and reflect the urinary protein excretion, suggesting a potential role in the pathogenesis of proteinuria in lupus nephritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/urinary-heparanase-activity-is-elevated-in-patients-with-lupus-nephritis-and-correlate-with-protein-excretion/