Serum 25-hydroxyvitamin D as a predictive biomarker of clinical outcomes in patients with primary membranous nephropathy

Suyan Duan; Si Chen; Fang Lu; Meng Zhou; Ling Jiang; Chen Chen; Luhan Geng; Rui Sun; Yili Xu; Zhimin Huang; Chengning Zhang; Bo Zhang; Huijuan Mao; Changying Xing; Yanggang Yuan

doi:10.3389/fnut.2023.1171216

Serum 25-hydroxyvitamin D as a predictive biomarker of clinical outcomes in patients with primary membranous nephropathy

Front Nutr. 2023 Apr 25:10:1171216. doi: 10.3389/fnut.2023.1171216. eCollection 2023.

Authors

Suyan Duan^#¹, Si Chen^#¹, Fang Lu¹, Meng Zhou¹, Ling Jiang¹, Chen Chen¹, Luhan Geng¹, Rui Sun¹, Yili Xu¹, Zhimin Huang¹, Chengning Zhang¹, Bo Zhang¹, Huijuan Mao¹, Changying Xing¹, Yanggang Yuan¹

Affiliation

¹ Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Background: Primary membranous nephropathy (PMN) is an immune-related disease with increased morbidity and the most common cause of adult nephrotic syndrome (NS). The serum 25-hydroxyvitamin D [25(OH)D)], a biomarker of vitamin D (VD) status, tends to decline in patients with kidney disease. However, the relationship between 25(OH)D and PMN is still unclear. Therefore, this study aims to clarify the association between 25(OH)D and disease severity and therapy response of PMN.

Methods: A total of 490 participants diagnosed with PMN by biopsy from January 2017 to April 2022 were recruited at the First Affiliated Hospital of Nanjing Medical University. The correlations between baseline 25(OH)D and manifestations of nephrotic syndrome (NS) or seropositivity of anti-PLA2R Ab were confirmed by univariate and multivariate logistic analyses. Spearman's correlations were used to examine the associations between baseline 25(OH)D and other clinical parameters. In the follow-up cohort, Kaplan-Meier analysis was used to assess remission outcomes among groups with low, medium, and high levels of 25(OH)D. Furthermore, the independent risk factors for non-remission (NR) were explored by COX regression analysis.

Results: At baseline, 25(OH)D was negatively related to 24-h urinary protein and serum anti-PLA2R Ab. The lower level of baseline 25(OH)D was associated with an increased risk for the incidence of NS in PMN (model 2, OR 6.8, 95% CI 4.4, 10.7, P < 0.001) and seropositivity of anti-PLA2R Ab (model 2, OR 2.4, 95% CI 1.6, 3.7, P < 0.001). Furthermore, the lower level of 25(OH)D during follow-up was demonstrated as an independent risk factor for NR even after adjusting age, gender, MBP, 24 h UP, serum anti-PLA2R Ab, serum albumin, and serum C3 [25(OH)D (39.2-62.3 nmol/L): HR 4.90, 95% CI 1.02, 23.53 P = 0.047; 25(OH)D < 39.2 nmol/L: HR 17.52, 95% CI 4.04, 76.03 P < 0.001); vs. 25(OH)D ≥ 62.3 nmol/L]. The Kaplan-Meier survival analysis also demonstrated that the higher level of follow-up 25(OH)D had a higher possibility of remission than the lower one (log-rank test, P < 0.001).

Conclusion: Baseline 25(OH)D was significantly correlated with nephrotic proteinuria and seropositivity of anti-PLA2R Ab in PMN. As an independent risk factor for NR, a low level of 25(OH)D during follow-up might serve as a prognostic tool for sensitively identifying cases with a high probability of poor treatment response.

Keywords: 25 (OH) vitamin D; anti-phospholipase A2 receptor antibody; predictor; primary membranous nephropathy; proteinuria.

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (82170699 and 81870469 to YY and 82100767 to SD), the Natural Science Foundation of Jiangsu Province (BK20191075 to SD), “PRO•Run” Fund of the Nephrology Group of CEBM (KYJ202206–0003-6 to YY), the “333 Project” of Jiangsu Province, the Six Talent Peaks Project in Jiangsu Province (WSN-010 to YY), “Yiluqihang⋅Shenmingyuanyang” Medical Development and Scientific Research Fund Project on Kidney Diseases (SMYY20220301001 to YY), Project of Clinical Capability Improvement of the First Affiliated Hospital of Nanjing Medical University (JSPH-MC-2021-14 to SD), Project of Bethune PuAi Medical Research Fund (PAYJ-058 to SD), Postgraduate Research & Practice Innovation Program of Jiangsu Province (JX10213856 to MZ), and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institution.