Podocyte Injury and Long-term Kidney Prognosis in Patients with Lupus Nephritis

Background: Lupus nephritis (LN) is a major complication of systemic lupus erythematosus. Like other types of glomerulonephritis, podocyte injury has been observed in patients with LN. However, the association between podocyte injury and kidney prognosis in patients with LN has not been well elucidated. This study aimed to explore the association between podocyte injury and clinical and histological status and kidney prognosis in patients with LN.

Methods: Seventy-five patients histopathologically diagnosed with LN were enrolled in this study. Early growth response 1 (EGR1) expression in podocytes, representing podocyte injury, was detected through immunohistochemistry. The correlation between the proportion of glomeruli with podocytes expressing EGR1 (%EGR1glo) and the clinical and histological features of LN was evaluated. Subsequently, the association between %EGR1glo and kidney prognosis was examined in a group of patients with LN classes III, IV, or V who showed ≥ 0.5 g/g of urinary protein-to-creatinine ratio (UPCR) and received immunosuppressive therapy. Hazard ratio was calculated using univariate Cox proportional hazards regression.

Results: %EGR1glo was highest in patients with LN class IV, significantly correlated with Systemic Lupus Erythematosus Disease Activity Index score, urinary protein level, and the prevalence of glomeruli showing cellular/fibrocellular crescents, endocapillary hypercellularity, and fibrinoid necrosis, and inversely correlated with eGFR. Higher %EGR1glo was significantly associated with sustained ≥ 30% eGFR decline over 10 years in patients with LN classes III, IV, or V (n = 42) (hazard ratio, 1.58 [95% confidence interval, 1.07-2.36] per 10% increase in %EGR1glo). There was no significant interaction between patients grouped by kidney function, urinary proteinuria level, presence of cellular/fibrocellular crescents, degree of tubulointerstitial fibrosis, and LN classification.

Conclusions: Podocyte damage, as indicated by EGR1 expression, was associated with poor long-term kidney prognosis in patients with active LN. Treatment strategies based on the extent of podocyte injury may be necessary.