Helper T‐cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques

Abstract

Objectives To elucidate the difference in the lithogenesis of calcium oxalate and calcium phosphate stones. Methods Renal papillary tissues were obtained from 23 idiopathic calcium oxalate and seven calcium phosphate stone patients who had undergone endoscopic lithotripsy. Samples were individually collected from two different regions in each patient: the papillary mucosa containing Randall's plaque and mucosa not containing Randall's plaque. A microarray analysis was carried out on those tissues to compare their gene expression patterns. Furthermore, a causal pathway analysis comparing their differences was carried out. Results Cluster analysis showed that gene expression profiles of calcium phosphate stone patients markedly differed from those of calcium oxalate stone patients. Disease and function analysis showed that Randall's plaque‐containing tissues of calcium phosphate stone‐forming patients had significantly higher movement and migration of mononuclear leukocytes, and lower tendency toward infection and lymph node formation than Randall's plaque‐containing tissues of calcium oxalate stone formers. Additional pathway analysis showed increased immune cell signaling in calcium phosphate formers, such as the helper T cell 1 and 2 pathways, which was confirmed by their messenger ribonucleic acid expression. Conclusions The present results show the upregulation of helper T‐cell signaling pathways in Randall's plaque‐containing papillae in calcium phosphate, but not in calcium oxalate stone formers. Thus, helper T‐cell immune responses and the related inflammatory processes seem to lead to the formation of calcium phosphate stones on Randall's plaques.

Inflammatory Cells in Nephrectomy Tissue from Patients without and with a History of Urinary Stone Disease

“…This study did not reveal a significant difference in the cortical or medullary T lymphocyte distribution of nonstone formers compared with stone formers. Upregulation of the T helper signaling pathway within the Randall’s plaque-containing papilla of calcium phosphate stone formers has been reported (31), and other studies suggest the possibility that T cell stimulation is followed by macrophage activation (32). It has also been reported that T cell migration was stimulated by treatment with exosomes derived from calcium oxalate–treated macrophages (29).…”

Bisphosphonate Use May Reduce the Risk of Urolithiasis in Astronauts on Long‐Term Spaceflights

“…Finally, we did not assess bone resorptive inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. We have reported that these cytokines can trigger inflammatory macrophage activation and induce renal stone formation in mice and humans (24)(25)(26)(27)(28)(29) . In addition, IL-1β and TNF-α are increased during spaceflight, with a trend for increased IL-6 (30).…”

“…We have reported that these cytokines can trigger inflammatory macrophage activation and induce renal stone formation in mice and humans. ( 24 , 25 , 26 , 27 , 28 , 29 ) In addition, IL‐1β and TNF‐α are increased during spaceflight, with a trend for increased IL‐6. ( 30 ) Further studies are needed to assess changes in these blood and urinary cytokines as risk factors for renal stone formation during spaceflight.…”

Osteopontin: An important protein in the formation of kidney stones

“…In the renal papillae containing the Randall’s plaques (thought to be the starting point of stone formation), the helper T-cell signaling pathway protein is upregulated. Thus, helper T-cell immune responses and associated inflammatory processes appear to lead to the formation of calcium phosphate stones on Randall’s plaques ( Taguchi et al, 2019 ).…”