Therapeutic Mechanism of Glucocorticoids on Cellular Crescent Formation in Patients With Antiglomerular Basement Membrane Disease

Abstract

Background: This study aimed to explore the therapeutic mechanism of glucocorticoids (GCs) in antiglomerular basement membrane disease.

Materials and methods: Thirty-four patients with biopsy-proven antiglomerular basement membrane nephritis were divided into the following 2 groups: group 1 (patients treated with GCs, n = 22) and group 2 (patients who were not treated with GCs, n = 12). The expression of parietal epithelial cells (PECs), activated PECs and glucocorticoid receptors (GRs) was examined quantitatively and compared between the 2 groups. Correlations between GR expression in glomeruli and patients' clinicopathological indices were also analyzed.

Results: Compared with patients in group 2, patients in group 1 showed lower levels of serum creatinine (SCr) (P = 0.03), average cellular crescent percentage (P = 0.005) and macrophages infiltrating in renal interstitium (P = 0.03). PECs (P = 0.007) and activated PECs (P = 0.03) were strongly detected in the cellular components of classic crescents, and both were significantly reduced in group 1 compared to group 2. GR expression either in glomeruli (P = 0.01) or interstitium (P = 0.009) was lower in group 1 after GCs treatment than in group 2. Additionally, GR expression in glomeruli was strongly correlated with renal function (SCr: r = 0.45, P = 0.009; eGFR: r = -0.35, P = 0.046), the proportion of cellular crescents (r = 0.67, P < 0.001), PECs (r = 0.64, P < 0.001) and activated PECs (r = 0.72, P < 0.001), and the degree of interstitial (r = 0.50, P = 0.004) and glomerular (r = 0.49, P = 0.007) macrophage infiltration.

Conclusions: GCs might exert their therapeutic effects via inhibiting the activation and proliferation of PECs, as well as macrophage infiltration, which could contribute to crescent formation and determine renal survival. GRs are involved in this process as well.

Keywords: Activation and proliferation; Crescent; Glucocorticoid receptor; Glucocorticoids; Parietal epithelial cells.