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Role of fibroblast growth factor-23 in renal disease activity and bone density involvement in patients with lupus nephritis
Nashwa M Azoz, Ammar A Ammar, Howaida A Nafady, Rabea A Gadelkareem, Essam M Abdel Aziz, Randa A Elzohne
Nashwa M Azoz, Ammar A Ammar, Essam M Abdel Aziz, Internal Medicine-Nephrology Division, Assiut University Hospital, Faculty of Medicine, Assiut University, Assiut 71711, Egypt
Howaida A Nafady, Internal Medicine-Clinical Hematology Unit, Assiut University Hospital, Faculty of Medicine, Assiut University, Assiut 71711, Egypt
Rabea A Gadelkareem, Department of Urology, Assiut Urology and Nephrology Hospital, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Randa A Elzohne, Department of Clinical Pathology, Assiut University Hospital, Faculty of Medicine, Assiut University, Assiut 71711, Egypt
Randa A Elzohne, Department of Clinical Pathology, Badr University in Assiut, New Nasser City 82516, Assiut, Egypt
Author contributions: Azoz NM and Ammar AA designed the research, collected the data, and wrote the paper; Nafady HA and Elzohne RA contributed to literature review, writing, revision, and supervision of the work; Gadelkareem RA and Abdel Aziz EM contributed to statistical analysis, literature review, writing, and revision; all authors approved the paper.
AI contribution statement: A few parts were assessed using an online program for language polishing, and they are now revised manually.
Institutional review board statement: The proposal of this study was approved by the Ethics Committee of the Faculty of Medicine, Assiut University, Egypt, on March 11, 2025. The institutional review board number is 04-2025-100349.
Informed consent statement: All participants provided informed consent.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Rabea A Gadelkareem, Assistant Professor, Department of Urology, Assiut Urology and Nephrology Hospital, Faculty of Medicine, Assiut University, Elgamaa Street, Assiut 71515, Egypt.
rabeagad@aun.edu.eg
Received: February 24, 2026
Revised: March 17, 2026
Accepted: May 13, 2026
Published online: September 25, 2026
Processing time: 171 Days and 6 Hours
BACKGROUND
Systemic lupus erythematosus-associated lupus nephritis (LN) represents a major contributor to disease-related morbidity. Disturbances in bone metabolism frequently coexist with LN, driven in part by persistent inflammation and impaired renal function. These factors are closely linked to decreased bone mineral density (BMD) and a heightened risk of fractures. Fibroblast growth factor-23 (FGF-23) has recently been recognized as a key regulator of mineral homeostasis and may serve as a marker reflecting both renal disease activity and skeletal involvement. Nevertheless, its precise role in LN activity and its impact on bone health remain inadequately defined.
AIM
To determine the predictive value of FGF-23 in renal disease activity and bone density changes in patients with LN.
METHODS
A cross-sectional hospital-based study included 100 adult patients with LN. Patients were classified into active (n = 50) and inactive LN (n = 50). All patients underwent clinical assessment, laboratory investigations, renal imaging, renal biopsy when indicated, and BMD assessment using dual-energy X-ray absorptiometry. Serum FGF-23 was measured using enzyme-linked immunosorbent assay. Statistical analysis included comparative tests, correlation analysis, logistic regression, and receiver operating characteristic curve analysis.
RESULTS
Patients with active LN had significantly higher FGF-23 levels compared with those with inactive LN (149.44 ± 37.09 pg/mL vs 122.56 ± 36.91 pg/mL; P < 0.001). BMD was significantly lower in patients with active LN (0.42 ± 0.19 g/cm² vs 0.56 ± 0.16 g/cm²; P < 0.001), with low BMD observed in 80% of patients with active LN vs 26% of those with inactive LN. FGF-23 level showed a significant negative correlation with BMD (r = -0.67, P = 0.001). Elevated FGF-23 level independently predicted low BMD (odds ratio = 4.18) and active LN (odds ratio = 2.18). At a cut-off point of ≥ 135 pg/mL, FGF-23 predicted low BMD with 79.5% accuracy.
CONCLUSION
FGF-23 may be a promising biomarker for renal disease activity and BMD in patients with LN. Its elevation may reflect the interplay between disturbances in mineral metabolism, inflammatory processes, and renal involvement. Nevertheless, further large-scale, longitudinal studies are required to validate these observations and clarify the clinical utility of FGF-23 in patients with LN.
Core Tip: Fibroblast growth factor-23 (FGF-23) regulates mineral metabolism and may reflect both renal activity and skeletal involvement. The present study demonstrated that serum FGF-23 levels were significantly associated with renal disease activity and bone mineral density (BMD) in patients with lupus nephritis. Elevated FGF-23 levels were correlated with impaired renal function and reduced BMD. Therefore, FGF-23 may be a valuable biomarker of renal disease activity and the risk of bone loss. Routine assessment of serum FGF-23 in patients with lupus nephritis may aid in risk stratification and disease monitoring. Additionally, those patients should undergo regular evaluation of BMD parameters.
