Urinary podocyte and TGF-β1 mRNA as markers for disease activity and progression in anti-glomerular basement membrane nephritis.

Publication Type:

Journal Article

Source:

Nephrol Dial Transplant, Volume 32, Issue 11, p.1818-1830 (2017)

Abstract:

Background: Podocyte depletion causes glomerulosclerosis, with persistent podocyte loss being a major factor driving disease progression. Urinary podocyte mRNA is potentially useful for monitoring disease progression in both animal models and in humans. To determine whether the same principles apply to crescentic glomerular injury, a rat model of anti-glomerular basement membrane (anti-GBM) nephritis was studied in parallel with a patient with anti-GBM nephritis.

Methods: Podocyte loss was measured by Wilms' Tumor 1-positive podocyte nuclear counting and density, glomerular epithelial protein 1 or synaptopodin-positive podocyte tuft area and urinary podocyte mRNA excretion rate. Glomerulosclerosis was evaluated by Azan staining and urinary transforming growth factor (TGF)-β1 mRNA excretion rate.

Results: In the rat model, sequential kidney biopsies revealed that after a threshold of 30% podocyte loss, the degree of glomerulosclerosis was linearly associated with the degree of podocyte depletion, compatible with podocyte depletion driving the sclerotic process. Urinary podocyte mRNA correlated with the rate of glomerular podocyte loss. In treatment studies, steroids prevented glomerulosclerosis in the anti-GBM model in contrast to angiotensin II inhibition, which lacked a protective effect, and urinary podocyte and TGF-β1 mRNA markers more accurately reflected both the amount of podocyte depletion and the degree of glomerulosclerosis compared with proteinuria under both scenarios. In a patient successfully treated for anti-GBM nephritis, urinary podocyte and TGB-β1 mRNA reflected treatment efficacy.

Conclusion: These results emphasize the role of podocyte depletion in anti-GBM nephritis and suggest that urinary podocyte and TGF-β1 mRNA could serve as markers of disease progression and treatment efficacy.