Calcium Phosphate-Induced Injury in Kidney Tubular Cells-Supersaturated Solution vs Preformed Crystals

Authors

Onyebuchi C. Ukaeje, Calcium Signaling Laboratory, Veterans Affairs Medical Center, Research Service, Washington, District of Columbia, USA.
Sanjit K. Roy, Calcium Signaling Laboratory, Veterans Affairs Medical Center, Research Service, Washington, District of Columbia, USA.
Samuel Shin, Calcium Signaling Laboratory, Veterans Affairs Medical Center, Research Service, Washington, District of Columbia, USA.
Sumiyya Raheem, Calcium Signaling Laboratory, Veterans Affairs Medical Center, Research Service, Washington, District of Columbia, USA.
Cory Reyes, Calcium Signaling Laboratory, Veterans Affairs Medical Center, Research Service, Washington, District of Columbia, USA.
Bidhan C. Bandyopadhyay, Calcium Signaling Laboratory, Veterans Affairs Medical Center, Research Service, Washington, District of Columbia, USA.

Document Type

Journal Article

Publication Date

2-1-2025

Journal

Journal of biochemical and molecular toxicology

Volume

39

Issue

2

DOI

10.1002/jbt.70145

Keywords

apoptosis; calcium phosphate crystals; crystalline nephropathy; necrosis; oxidative stress; proximal tubular cells; supersaturated solution

Abstract

Crystalline nephropathy (CN) is characterized by deposition of microcrystals within the kidney tubular microstructure, specifically in the renal tubular cells. Nephropathic conditions have been observed in kidney stone patients as nephrocalcinosis, resulting from the deposition of calcium phosphate (CaP) microcrystals mainly within the renal tubule. CaP microcrystals trigger nephrotoxicity and cell death leading to acute and chronic kidney disease and in some cases end stage renal disease. Although supersaturation of calcium (Ca)- and phosphate (PO ) ions in the urine was described as a main factor the precise mechanism of cell death by distinguishing the impact of supersaturated solution vs the crystalline substances is unclear. Here we show the differential effect of CaP solution vs preformed crystal (as crystalline CaP) on the nephrotoxicity and the degree and type of cell death using a murine kidney tubular cell line, LLCPK1. We examined the cellular [cell viability, lactate dehydrogenase (LDH) and HO releases and Annexin+ propidium iodide (PI) staining] and molecular events [gene expressions, oxidative and endoplasmic reticular (ER) stress] towards understanding the mechanism of CN. The results of the study demonstrated that CaP in solution exerts injury effect on LLCPK1 cells. The addition of CaP solution showed stronger necrosis than the preformed crystals as shown by PI staining and the releases of LDH and HO. Overall, the results in the study revealed a novel mechanism differentiating the kidney cell injury between the insult mediated by supersaturated CaP solution and preformed CaP crystals.

APA Citation

Ukaeje, Onyebuchi C.; Roy, Sanjit K.; Shin, Samuel; Raheem, Sumiyya; Reyes, Cory; and Bandyopadhyay, Bidhan C., "Calcium Phosphate-Induced Injury in Kidney Tubular Cells-Supersaturated Solution vs Preformed Crystals" (2025). GW Authored Works. Paper 6658.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6658

Department

Medicine