Urinary extracellular vesicle-associated MCP-1 and NGAL derived from specific nephron segments differ between calcium oxalate stone formers and controls

Robin S. Chirackal, Muthuvel Jayachandran, Xiangling Wang, Samuel Edeh, Zejfa Haskic, Majuran Perinpam, Timothy M. Halling, Ramila Mehta, Marcelino E. Rivera, John C. Lieske

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)F1475-F1482
JournalAmerican journal of physiology. Renal physiology
Volume317
Issue number6
DOIs
StatePublished - Dec 1 2019

Fingerprint

Calcium Oxalate
Chemokine CCL2
Nephrons
Calcium
Kidney Calculi
Biomarkers
Urine
Osteopontin
Kidney Diseases
Lipocalin-2
Extracellular Vesicles
Population
Membrane Proteins
Antibodies

Keywords

  • extracellular vesicles
  • monocyte chemoattractant protein-1
  • nephrolithiasis
  • neutrophil gelatinase-associated lipocalin
  • Randall’s plaque
  • urinary stone disease

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Urinary extracellular vesicle-associated MCP-1 and NGAL derived from specific nephron segments differ between calcium oxalate stone formers and controls. / Chirackal, Robin S.; Jayachandran, Muthuvel; Wang, Xiangling; Edeh, Samuel; Haskic, Zejfa; Perinpam, Majuran; Halling, Timothy M.; Mehta, Ramila; Rivera, Marcelino E.; Lieske, John C.

In: American journal of physiology. Renal physiology, Vol. 317, No. 6, 01.12.2019, p. F1475-F1482.

Research output: Contribution to journalArticle

Chirackal, Robin S. ; Jayachandran, Muthuvel ; Wang, Xiangling ; Edeh, Samuel ; Haskic, Zejfa ; Perinpam, Majuran ; Halling, Timothy M. ; Mehta, Ramila ; Rivera, Marcelino E. ; Lieske, John C. / Urinary extracellular vesicle-associated MCP-1 and NGAL derived from specific nephron segments differ between calcium oxalate stone formers and controls. In: American journal of physiology. Renal physiology. 2019 ; Vol. 317, No. 6. pp. F1475-F1482.
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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.

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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.

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