# Hemoglobin-associated CALR in proximal tubule cells can be used as a biomarker for idiopathic membranous nephropathy

**Authors:** Shuting Pang, Qiuyan Tan, Boji Xie, Bingmei Feng, Rongbin Zhou, Zige Liu, Haiyuan Wei, Yian Huang, Mujia Jili, Yuli Xie, Shanshan Li, Binran Zhao, Wei Li, Rirong Yang

PMC · DOI: 10.3389/fmed.2025.1574852 · Frontiers in Medicine · 2025-06-11

## TL;DR

Researchers found that the CALR gene in kidney cells can serve as a biomarker for idiopathic membranous nephropathy, a leading cause of adult kidney disease.

## Contribution

The study identifies CALR as a novel biomarker and explores its role in immune and physiological processes related to idiopathic membranous nephropathy.

## Key findings

- CALR is significantly associated with the development and progression of idiopathic membranous nephropathy.
- CALR is involved in immune response and hemoglobin production, highlighting its dual functional roles.
- Validation through RNA-seq, immunohistochemistry, and qRT-PCR confirmed CALR's relevance in the disease.

## Abstract

Idiopathic membranous nephropathy (IMN) is the leading cause of nephrotic syndrome in adults. Given the limited diagnostic options currently available, we performed RNA sequencing (RNA-seq) of urinary cells to identify potential urinary biomarkers for IMN and to investigate its underlying disease mechanisms.

We conducted RNA-seq analysis on cells isolated from both first-void and second-void morning urine samples. By integrating these data with single-cell RNA sequencing (scRNA-seq) data from IMN and healthy kidney tissues, we performed comprehensive analyses including: Inflammatory index assessment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Ontology (GO) functional annotation, Gene Set Enrichment Analysis (GSEA) enrichment analysis, Protein-Protein Interaction (PPI) network construction. Candidate differentially expressed genes (DEGs) were further validated using urinary cell RNA-seq data. Key genes were ultimately identified through Weighted Gene Co-expression Network Analysis (WGCNA) and subsequently verified by immunohistochemical and Quantitative Real-Time PCR (qRT-PCR) experiments of tissue expression patterns.

Our findings demonstrate that the CALR gene is significantly associated with IMN pathogenesis and progression. Functionally, CALR plays crucial roles in both immune response (particularly in antigen presentation) and physiological processes (notably in hemoglobin production).

## Linked entities

- **Genes:** CALR (calreticulin) [NCBI Gene 811]
- **Diseases:** idiopathic membranous nephropathy (MONDO:0013860), nephrotic syndrome (MONDO:0005377)

## Full-text entities

- **Genes:** CALR (calreticulin) [NCBI Gene 811] {aka CALR1, CRT, HEL-S-99n, RO, SSA, cC1qR}
- **Diseases:** Inflammatory (MESH:D007249), IMN (MESH:D015433), nephrotic syndrome (MESH:D009404)

## Full text

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## Figures

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## References

56 references — full list in the complete paper: https://tomesphere.com/paper/PMC12187741/full.md

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Source: https://tomesphere.com/paper/PMC12187741