The thickness of glomerular basement membrane predicts complete remission in primary membranous nephropathy

Abstract

Objective

Glomerular basement membrane (GBM) thickening is a typical and essential histopathological characteristic for the diagnosis of primary membranous nephropathy (PMN). The present study aimed to explore the relationship between GBM thickness and treatment response in PMN patients.

Methods

A total of 128 patients with nephrotic syndrome concurrent with PMN were studied. The highest GBM thickness was measured from at least five glomerular capillary loops using an electron microscope, and the mean value was obtained. Patients were categorized into three groups according to the tertiles of GBM thickness as follows: Group 1 (GBM thickness ≤ 1100 nm, n = 48), Group 2 (1100 nm < GBM thickness ≤ 1300 nm, n = 40), Group 3 (GBM thickness >1300 nm, n = 40). Clinicopathological features and treatment response were compared among the three groups. The associations of GBM thickness with complete remission (CR) were assessed by Cox proportional hazard analyses and a cubic spline curve.

Results

During a median follow-up period of 25.80 months, 69 (53.9%) patients achieved CR. Kaplan–Meier analysis showed that the non-CR probability was significantly higher in the highest tertile of GBM thickness (p˂0.001). Univariate Cox proportional hazard analysis indicated that GBM thickness was associated with CR (HR per SD 0.617, 95% CI [0.471–0.809], p˂0.001). After adjusting for age, duration of PMN, estimated glomerular filtration rate (eGFR), urinary protein excretion, grade of C3 deposition, and titer of serum anti-phospholipase A2 receptor (PLA2R) antibody, GBM thickness remained an independent predictor of CR (HR per SD 0.580, 95% CI [0.436–0.772], p˂0.001). Further multivariable-adjusted restricted cubic spline analysis confirmed a significant reverse linear association between GBM thickness and CR (p for nonlinear = 0.1261).

Conclusions

GBM thickness is an independent risk factor of CR. PMN patients with an increased level of GBM thickening at diagnosis have a lower probability of achieving CR.

Keywords:

• GBM thickness
• primary membranous nephropathy
• complete remission
• proteinuria

Acknowledgments

None.

Ethical approval

The research was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (approval number: No.2018-SR-250).

Informed consent

Informed consent was obtained from all patients included in the study.

Consent for publication

All authors gave consent for publication.

Author contributions

SD designed and conducted the research and analyzed the data. LS contributed substantially to the writing and critical review of the manuscript. CZ, MZ, BS, YY, and HM reviewed the manuscript. CX coordinated and conceived the study as well as revised the manuscript. BZ was the guarantor of this work and had complete access to all the data in the study. All authors have read the final paper and approved the submission.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (82100767), the Natural Science Foundation of Jiangsu Province (BK20191075), "PRO•Run" Fund of the Nephrology Group of CEBM, Project of clinical capability improvement of the First Affiliated Hospital of Nanjing Medical University(JSPH-MC-2021-14), Project of Beijng Bethune Charitable Foundation(PAYJ-058), and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institution.

This work was supported by grants from the National Natural Science Foundation of China (82100767), the Natural Science Foundation of Jiangsu Province (BK20191075), "PRO•Run" Fund of the Nephrology Group of CEBM, Project of clinical capability improvement of the First Affiliated Hospital of Nanjing Medical University (JSPH-MC-2021-14), Project of Bethune PuAi Medical Research Fund (PAYJ-058), and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institution.