Shang-Mei Li,1,* La-Wei Yang,2,* Zhi-Qing Huang,1 Jia-Ying Ma,1 Jiao-Hua Wu,1 Hua-Feng Liu,1,2 Yong-Zhi Xu,1,2 Mian-Na Luo1,2 

1Department of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, 524001, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, 524001, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Mian-Na Luo; Yong-Zhi Xu, Department of Nephrology, Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue South, Xiashan District, Zhanjiang, Guangdong Province, 524001, People’s Republic of China, Tel +86 13763015687, Email luomianna@126.com; lxyzhi@126.com

Objective: The role of crescent formation in primary membranous nephropathy (PMN) and its potential impact on prognosis remain an area of ongoing investigation. This study stratifies patients with PMN into two cohorts: one with crescents and one without. It then compares these groups to investigate the influence of crescents on the prognosis of PMN.
Methods: In this retrospective analysis, we included patients who had a confirmed diagnosis of PMN and exhibited crescents upon renal biopsy. The study population was sourced from the medical records at the Affiliated Hospital of Guangdong Medical University in Zhanjiang, China, spanning from January 2017 to June 2023. To enable a comparative analysis of clinical, pathological, and prognostic features, a control group was established, comprising 106 patients diagnosed with PMN who did not have crescent formation. These controls were randomly selected from the same time frame. Regular follow-up of the patients continued in the outpatient setting for at least six months.
Results: A total of 53 patients with PMN and crescent formation were included in this study, while 106 individuals without crescents served as a randomly selected control group. Patients with PMN and crescents exhibited higher systolic blood pressure (P = 0.015), 24-hour proteinuria (P = 0.006), serum creatinine (P = 0.029) levels, and lower glomerular filtration rate (P = 0.002), compared to those without crescents. Histological examination revealed a higher proportion of focal segmental sclerosis (P < 0.001), spherical sclerosis (P < 0.001), arteriosclerosis (P = 0.02), and interstitial fibrosis with tubular necrosis (P = 0.002) in patients with PMN and crescent formation. Immunofluorescence staining demonstrated a weaker IgG4 fluorescence intensity in patients with PMN and crescent formation. At the end of the follow-up period, patients with PMN and crescents had a lower remission rate (P = 0.022), poorer renal function (P = 0.007), and lower albumin (P = 0.039) levels. Kaplan-Meier (KM) analysis identified proteinuria and crescent formation as independent risk factors for adverse outcomes in patients with PMN (P < 0.001 and P < 0.05). Immunohistochemistry staining revealed positive expression of CD68 and CD20 in the renal interstitium of patients with PMN, regardless of the presence of crescents.
Conclusion: Crescent formation is associated with a risk of adverse outcomes in patients with PMN. Patients with crescents exhibit severe clinical and pathological features and have poorer prognoses.

Keywords: crescents, primary membranous nephropathy, risk factor