TY - JOUR
T1 - Urinary extracellular vesicle-associated MCP-1 and NGAL derived from specific nephron segments differ between calcium oxalate stone formers and controls
AU - Chirackal, Robin S.
AU - Jayachandran, Muthuvel
AU - Wang, Xiangling
AU - Edeh, Samuel
AU - Haskic, Zejfa
AU - Perinpam, Majuran
AU - Halling, Timothy M.
AU - Mehta, Ramila
AU - Rivera, Marcelino E.
AU - Lieske, John C.
N1 - Funding Information:
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant U54 DK-100227 from the O'Brien Urology Research Center, Rare Kidney Stone Consortium Grant U54 DK-083908, part of the Rare Diseases Clinical Research Network, an initiative of ORDR, NCATS, and NIDDK, and the Mayo Foundation.
Funding Information:
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant U54 DK-100227 from the O’Brien Urology Research Center, Rare Kidney Stone Consortium Grant U54 DK-083908, part of the Rare Diseases Clinical Research Network, an initiative of ORDR, NCATS, and NIDDK, and the Mayo Foundation.
Publisher Copyright:
Copyright © 2019 the American Physiological Society.
PY - 2019
Y1 - 2019
N2 - Randall's plaque (RP; subepithelial calcification) appears to be an important precursor of kidney stone disease. However, RP cannot be noninvasively detected. The present study investigated candidate biomarkers associated with extracellular vesicles (EVs) in the urine of calcium stone formers (CSFs) with low (<5% papillary surface area) and high (≥5% papillary surface area) percentages of RP and a group of nonstone formers. RPs were quantitated via videotaping and image processing in consecutive CSFs undergoing percutaneous surgery for stone removal. Urinary EVs derived from cells of different nephron segments of CSFs (n = 64) and nonstone formers (n = 40) were quantified in biobanked cell-free urine by standardized and validated digital flow cytometer using fluorophore-conjugated antibodies. Overall, the number of EVs carrying surface monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL) were significantly lower in CSFs compared with nonstone former controls (P < 0.05) but did not differ statistically between CSFs with low and high RPs. The number of EVs associated with osteopontin did not differ between any groups. Thus, EVs carrying MCP-1 and NGAL may directly or indirectly contribute to stone pathogenesis as evidenced by the lower of these populations of EVs in stone formers compared with nonstone formers. Validation of EV-associated MCP-1 and NGAL as noninvasive biomarkers of kidney stone pathogenesis in larger populations is warranted.
AB - Randall's plaque (RP; subepithelial calcification) appears to be an important precursor of kidney stone disease. However, RP cannot be noninvasively detected. The present study investigated candidate biomarkers associated with extracellular vesicles (EVs) in the urine of calcium stone formers (CSFs) with low (<5% papillary surface area) and high (≥5% papillary surface area) percentages of RP and a group of nonstone formers. RPs were quantitated via videotaping and image processing in consecutive CSFs undergoing percutaneous surgery for stone removal. Urinary EVs derived from cells of different nephron segments of CSFs (n = 64) and nonstone formers (n = 40) were quantified in biobanked cell-free urine by standardized and validated digital flow cytometer using fluorophore-conjugated antibodies. Overall, the number of EVs carrying surface monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL) were significantly lower in CSFs compared with nonstone former controls (P < 0.05) but did not differ statistically between CSFs with low and high RPs. The number of EVs associated with osteopontin did not differ between any groups. Thus, EVs carrying MCP-1 and NGAL may directly or indirectly contribute to stone pathogenesis as evidenced by the lower of these populations of EVs in stone formers compared with nonstone formers. Validation of EV-associated MCP-1 and NGAL as noninvasive biomarkers of kidney stone pathogenesis in larger populations is warranted.
KW - Extracellular vesicles
KW - Monocyte chemoattractant protein-1
KW - Nephrolithiasis
KW - Neutrophil gelatinase-associated lipocalin
KW - Randall's plaque
KW - Urinary stone disease
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U2 - 10.1152/ajprenal.00515.2018
DO - 10.1152/ajprenal.00515.2018
M3 - Article
C2 - 31461349
AN - SCOPUS:85076065582
SN - 0363-6127
VL - 317
SP - F1475-F1482
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 6
ER -