Login to Access Video or Poster Abstract: MP19-19
Sources of Funding: NIDDK U54 DK100227

Introduction

Randall’s plaques (RP) appear to be an important precursor of urinary stone disease. However, RP cannot be noninvasively detected. Furthermore, the biologic processes that mediate growth of RP remain unclear. This study was designed to identify specific micro RNA (miRNAs) changes within urinary extracellular vesicles (EVs) based on stone forming status, and the amount of intrarenal RP.

Methods

A total of 40 subjects were included in this study. First time (incident) stone formers and population controls were recruited from the community (n=10 each). RP were assessed via endoscopic digital imaging with quantitative analysis in consecutive idiopathic calcium oxalate stone formers undergoing percutaneous surgery for stone removal. Subjects with high amounts of RP (HP; > 5% papillary surface area coverage; n=10) were age (+/- 5 yrs) and sex matched to a group with low amounts of RP (LP; < 5% papillary surface area coverage; n=10). Small non-coding miRNAs within urinary EVs were quantitated by XRNA Exosome RNA-Seq Library Kit (System Biosciences, Palo Alto, CA). Differentially expressed miRNAs with a p-value of 0.05 or lower were chosen for pathway analysis and miRNA target prediction comparing LP versus HP, and population controls versus stone formers.

Results

When controls were compared to stone formers, a total of 10 miRNA were increased (6 to 10-fold), while 5 miRNA were decreased (2 to 5-fold). When LP were compared to HP stone formers, 3 miRNA were increased (6.5 to 10-fold) while 7 miRNA were decreased (6-9 fold). The upregulated miRNAs contribute in calcification, cell proliferation, acute kidney injury, renal fibrosis, pro-apoptotic and pro-inflammatory pathways whereas down-regulated miRNAs contribute anti-apoptotic and anti-inflammatory processes, prevent renal fibrosis, ischemic injury, and progression of chronic kidney disease.

Conclusions

Stone formers and those with high amounts of RP excrete distinct populations of miRNAs within urinary EVs. These miRNAs may serve as novel biomarkers to indicate the presence of RP. These miRNAs may also provide new insights into early renal cellular processes in the progression of stone pathogenesis and RP and new tools for the screening, diagnosis, risk stratification and monitoring of pharmacological therapy for persons with idiopathic stone disease. Further studies to validate and extend these observations are needed.

Funding

NIDDK U54 DK100227