Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers

Zhang, Jiqing; Kumar, Sanjay; Jayachandran, Muthuvel; Wang, Stanley; Wilson, Elena; Lieske, John C.

doi:10.21203/rs.3.rs-64903/v1

Cited by 1 publication

(1 citation statement)

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“…However, CD68 gene expression did not differ between nonstone formers and stone formers (19). A recent study published by our group demonstrated that urinary excretion of CD68-positive extracellular vesicles (derived from activated M1 macrophages) was significantly lower in stone formers compared with nonstone formers, suggesting greater intrarenal expression of proinflammatory macrophages and their vesicles within stone formers (30). In addition, experiments using a hyperoxaluric experimental mouse model demonstrated that daily intra-abdominal administration of IL-4 and IL-13 and transfusion of CD206-positive macrophages increased intrarenal M2 macrophage accumulation and suppressed calcium oxalate crystal formation compared with a control group (25).…”

Section: Discussionmentioning

confidence: 98%

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

Dejban

Wilson

Jayachandran

et al. 2022

CJASN

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Background and objectives: Urinary stone disease has been associated with inflammation, but the specific cell interactions that mediate events remain poorly defined. This study compared calcification and inflammatory cell patterns in kidney tissue from radical nephrectomy specimens of patients without and with a history of urinary stone disease. Design, setting, participants, and measurements: Non-tumor parenchyma of biobanked radical nephrectomy specimens from age- and sex-matched stone formers (n=44) and non-stone formers (n=82) were compared. Calcification was detected by Yasue staining and inflammatory cell populations by immunohistochemistry for CD68 (pro-inflammatory M1 macrophages), CD163 and CD206 (anti-inflammatory M2 macrophages), CD3 (T-lymphocytes), and tryptase (mast cells). Calcifications and inflammatory cells were quantified in cortex and medulla using Image-Pro® analysis software. Results: Calcification in the medulla of stone formers was higher than in non-stone formers (p<0.001). M1 macrophages in the cortex and medulla of stone formers were greater than in non-stone formers (p<0.001), and greater in stone former medulla than stone former cortex (p=0.02). There were no differences in age, sex, body mass index, tumor characteristics (size, stage, or thrombus), vacular disease status, or estimated glomerular filtration rate between the groups. M2 macrophages, T-lymphocytes, and mast cells did not differ by stone former status. There was a correlation between M1 macrophages and calcification in the medulla of stone formers (rho=0.48; p=0.001) and between M2 macrophages and calcification in the medulla of non-stone formers (rho=0.35; p=0.001). T-lymphocytes were correlated with calcification in the cortex of both non-stone formers (rho=0.27; p=0.01) and stone formers (rho=0.42; p=0.004) whereas mast cells and calcification were correlated only in cortex of stone formers (rho=0.35; p=0.02). Conclusions: Higher medullary calcification stimulated accumulation of pro-inflammatory rather than anti-inflammatory macrophages in stone formers.

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Section: Discussionmentioning

confidence: 98%