Kidney Week

Abstract: SA-PO0289

Kidney Cortex Macrophages Prevent the Formation of Mineral Stones by Reabsorbing Phosphate from the Urine

Session Information

• Bone and Mineral Metabolism: Basic Research
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 501 Bone and Mineral Metabolism: Basic

Authors

• Wang, Yuxi, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Yuxi Wang, MD

• Shen, Xiao, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Xiao Shen, MD

• Weng, Yuancheng, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Yuancheng Weng, PhD

• Han, Fei, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Fei Han, MD

Background

Resident macrophages play important roles beyond immunity to fulfill tissue-specific needs and handle specific stresses resident tissue routinely endures. Tubular obstruction by particles such as mineral stones is a continuous challenge to the kidney, but the roles of macrophages in kidney stone development are not fully addressed.

Methods

Knockout mice, transcriptomics data analysis, immunohistochemistry, flow cytometry analysis, cell culture, real-time PCR, blood and urine biochemical analyses.

Results

MØ in cortex and medulla differ in transcriptomes, Slc34a1, which encodes sodium-dependent phosphate transporter 2A, was notably expressed in the cortex MØ. Kidney MØ expressed a high level of SLC34A1 relative to other tissue MØ. Using ³²P, we proved that cortex MØ could uptake Pi in a SLC34A1-dependent manner.

Abrogation of Slc34a1 expression by cortex MØ resulted in an increased urinary Pi excretion, leading to a decrease of PTH with increased VD₃, but no overt hypophosphatemia. Thus, we fed Slc34a1^ΔMØ mice with a low-phosphorus diet, a more profound reduction of Pi concentration in plasma occurred in the mutated mice.

We estimated that SLC34A1-mediated Pi reabsorption by MØ was around ~20%. Thus the loss of MØ’s ability in reabsorbing Pi could place a threat to an oversaturation of Pi and CaPi crystal formation. We imaged the kidneys using a fluorescent bisphosphonate (OsteoSense) that can bind to crystalline CaPi, there were about 10-fold increase of OsteoSense⁺ crystals in Slc34a1^ΔMØ mice.

When the culture medium was supplemented with different doses of oversaturated CaPi, monocytes indeed responded by upregulating Slc34a1 expression. This pattern also happened when mice were fed high-phosphorous diet, and tubular epithelial cells were injured at the same time. We also observed the pattern in hydroxylapatite-induced vascular calcification.

Conclusion

In this study, we found that kidney cortex MØ distinguishably and highly express Slc34a1, deprivation of Slc34a1 expression in kidney MØ led to a urinary Pi excretion and a rampant CaPi microparticle deposition. The importance of MØ but not tubular epithelial cells in modulating Pi concentration in the urine was highlighted by their different responses to CaPi microcrystals. The cellular mechanisms involving MØ should be explored in the future for therapeutical application on kidney stone diseases.

Funding

• Government Support – Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025fqhhzzdq