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) percentage of RP and a group of non-stone formers. RP 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 non-stone formers (n=40) were quantified in bio-banked cell-free urine by standardized and validated digital flow cytometer using fluorophore-conjugated antibodies. Overall, the number of EVs carrying surface monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly lower in CSFs compared to non-stone former controls (p<0.05), but did not differ statistically between the CSFs with low and high RP. The number of EVs associated with osteopontin (opn) 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 to non-stone formers. Validation of EV-associated MCP-1 and NGAL as noninvasive biomarkers of kidney stone pathogenesis in larger populations is warranted.
American journal of physiology. Renal physiology. 2019 Aug 28 [Epub ahead of print]
Robin S Chirackal, Muthuvel Jayachandran, Xiangling Wang, Samuel Edeh, Zejfa Haskic, Majuran Perinpam, Timothy M Halling, Ramila Mehta, Marcelino E Rivera, John C Lieske
Division of Nephrology and Hypertension, Mayo Clinic, United States., Medical Sciences Building, Mayo Clinic College of Medicine, United States., Division of Hematology Research, Mayo Clinic, United States., Health Sciences Research, Mayo Clinic, United States., Department of Urology, Mayo Clinic, United States., Medicine, Mayo Clinic College of Medicine, United States.