Very small embryonic-like stem cells: A predictor synergizing with complement and inflammatory factors for immunoglobulin A nephropathy prognosis

Abstract

BACKGROUND

Immunoglobulin A nephropathy (IgAN), a common primary glomerular disease, may progress to end-stage renal disease (ESRD). Stem cells regulate renal repair by countering mesangial injury, but the prognostic value very small embryonic-like stem cells (VSELs) and their synergy with complement/inflammatory biomarkers in IgAN remain unclear. Single-pathway biomarkers are inaccurate for ESRD prediction, and combined stem cell-complement/inflammatory risk stratification awaits validation.

AIM

To clarify the independent prognostic value of VSELs, complement factor I (CFI), C3a, and tumor necrosis factor-α (TNF-α) in IgAN patients and explore whether their combined detection can improve the accuracy of ESRD prediction.

METHODS

A retrospective analysis was conducted on 255 IgAN patients from our hospital, who were stratified into ESRD (31 cases) and non-ESRD (224 cases) groups based on follow-up outcomes. Complement alternative pathway indices included complement factor B, CFI, C3a, complement factor H, and sC5b-9; inflammatory biomarkers included monocyte chemoattractant protein-1, interleukin-6, TNF-α, B-cell activating factor, and C-X-C motif chemokine ligand 10; stem cell indicators included VSELs, hematopoietic stem cells, and endothelial progenitor cells. Statistical methods included t-tests, χ² tests, Spearman correlation, Logistic regression, receiver operating characteristic curves, and Kaplan-Meier survival analysis.

RESULTS

IgAN patients in ESRD had lower complement factor B, CFI, C3a, and higher monocyte chemoattractant protein-1, interleukin-6, TNF-α, and VSELs compared to non-ESRD (all P < 0.001), with CFI, C3a, TNF-α, and VSELs as independent ESRD predictors (all P < 0.05). The combined detection of CFI, TNF-α, and VSELs showed a higher predictive value for ESRD [area under the curve (AUC) = 0.916] than single indicators (CFI: AUC = 0.660; TNF-α: AUC = 0.818; VSELs: AUC = 0.749). Spearman correlation analysis revealed that VSELs were weakly positively correlated with CFI and TNF-α, while estimated glomerular filtration rate was positively correlated with CFI and negatively correlated with TNF-α (all P < 0.05). High VSELs indicated poorer renal prognosis (P < 0.001), with no significant differences in renal survival for CFI or TNF-α (all P > 0.05).

CONCLUSION

VSELs, along with CFI and TNF-α, are independent predictors of ESRD in IgAN patients, with VSELs providing a more reliable indicator of poor renal prognosis. Their combined detection achieves high predictive accuracy (AUC = 0.916), offering a non-invasive prognostic tool independent of Oxford classification features, thus enhancing risk stratification and individualized intervention strategies.

Keywords: Complement alternative pathway; Stem cell indicators; Inflammatory markers; Immunoglobulin A nephropathy; Estimated glomerular filtration rate; End-stage renal disease

Core Tip: As a key stem cell indicator, very small embryonic-like stem cells, combined with complement alternative pathway indices and inflammatory biomarker tumor necrosis factor-α, are independent predictors of end-stage renal disease in immunoglobulin A nephropathy patients. Their combined detection yields high predictive accuracy, outperforming single indicators and enabling reliable risk stratification. High very small embryonic-like stem cells correlate with poor renal prognosis, and these serological markers predict outcomes independent of Oxford classification, providing a non-invasive alternative to renal biopsy and enriching individualized intervention biomarkers.