Association between Randall’s plaque and calcifying nanoparticles

Abstract

Objectives

Randall initially described calcified subepithelial papillary plaques, which he hypothesized as nidi for urinary calculi. The discovery of calcifying nanoparticles (CNP), also referred to as nanobacteria, in calcified soft tissues has raised another hypothesis about their possible involvement in urinary stone formation. This research is the first attempt to investigate the potential association of these two hypotheses.

Methods

We collected renal papilla and blood samples from 17 human patients who had undergone laparoscopic nephrectomy. Immunohistochemical staining (IHS) was applied using monoclonal antibody (mAb) against CNP. Homogenized papillary tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) were performed on papillary samples. Serum samples were tested for CNP antigen and antibody with enzyme-linked immunosorbent assay (ELISA).

Results

Randall’s plaques (RP) were visible on gross inspection in 11 out of 17 samples. IHS was positive for CNP antigen in 8 of the visually positive samples, but in only 1 of the remaining samples. SEM revealed spherical apatite-formations in 14 samples confirmed by EDS analysis. In cultures, all serum samples and 13 tissue homogenates grew CNP. In ELISA, 14 samples were positive for CNP-antigen and 11 samples were positive for CNP-antibody.

Conclusion

There was evidence of a link between detection of CNP and presence of RP. Although causality was not demonstrated, these results suggest that further studies with negative control samples should be made to explore the etiology of RP formation, thus leading to a better understanding of the pathogenesis of stone formation.

Keywords:

• calcifying nanoparticles
• nanobacteria
• Randall’s plaque
• urinary stone

Acknowledgements

This research was funded by ARES/Astrobiology at NASA Johnson Space Center (JSC), and Nanobac Pharmaceuticals Inc. We thank Dr Alan H Feiveson (NASA, JSC) for statistical analysis, Dr Adam Hittelman at University of California at San Francisco (UCSF) for coordinating patients’ serum and tissue samples, Dr Craig Schwandt (NASA, JSC) for his support in electron microscopy, and Dr Jean Olson (UCSF) for her assistance in evaluating immunohistochemistry interpretaton. Special thanks to Mission Pharmacal for providing discussion points on stone formation. Our gratitude to Dr Dan Garrison (NASA JSC) for his efficient management of BSL-2 laboratories and Charles Galindo (NASA, JSC) for his assistance. Patrice Colbert’s (NASA, JSC) proficiency in editing the text is greatly appreciated. The authors report no conflict of interest in this manuscript.