Non‐radiological assessment of kidney stones using the kidney injury test (KIT), a spot urine assay

Abstract

A total of 136 spot urine samples from 98 individuals, with and without kidney stone disease, were processed in a predefined assay to measure six DNA and protein markers in order to generate a risk score for the non-invasive detection of nephrolithiasis. From this cohort, 56 individuals had spot, non-timed urine samples collected at the time of radiographically confirmed kidney stones, and 54 demographically matched, healthy controls without kidney stone disease also provided spot, non-timed urine samples. Sixteen individuals with persistent stone disease had more than one urine sample. Using a proprietary microwell-based KIT assay, we measured cell-free DNA (cfDNA), methylated cfDNA, clusterin, creatinine, protein and CXCL10. A KIT stone score was computed across all markers using the prior locked KIT algorithm. The KIT stone score, with a scale of 0 to 100, was then correlated with demographic variables, kidney stone burden, obstructive kidney stone disease, and urine solutes in 24-h urine collections. ResultsThe scaled KIT stone score, a composite of all six biomarkers, readily discriminated individuals with current or prior radiographically confirmed kidney stones from healthy controls without kidney stone disease (P < 0.001). In individuals with nephrolithiasis, KIT stone score also correlated with radiologically measured stone size (P = 0.017) and differentiated patients with a clinical radiological diagnosis of obstructive nephrolithiasis associated with upper renal tract dilatation (P = 0.001). Stone burden as assessed by KIT stone score, however, did not correlate with the any of the traditional measures of 24-h urine solutes or the 24-h urine supersaturation levels. In patients with persistent stone disease, where multiple urine samples were collected over time and after different interventions, the use of KIT stone score could non-invasively track stone burden over time through a spot urine, non-timed urine sample. ConclusionsA random, spot urine-based assay, KIT stone score, can noninvasively detect, quantify and monitor current stone burden, and may thus minimize radiographic exposure for kidney stone detection. The KIT stone score assay may also help monitor stone recurrence risk for patients with nephrolithiasis, without the requirement for 24-h urine collections.

Macrophage Function in Calcium Oxalate Kidney Stone Formation: A Systematic Review of Literature

“…However, evidence regarding Mφs in urinary sediments is scant, and the direct manipulation of Mφ phenotypes for clinical use needs to be determined ( 56 ). Future investigations should strive to establish a urinary biomarker for liquid biopsies ( 57 ), and an Mφ-specific target therapy using antibodies, vectors, and nanoparticles ( 58 , 59 ).…”

A large staghorn stone diagnosed and managed in an asymptomatic patient using the “Kidney Injury Test (Kit)” spot urine assay: A case report

“…The KIT Score could risk-stratify stone recurrence and provide an objective measure of kidney stone burden with a lower limit of detection of 2 mm. 3 Higher levels are present in obstructive compared to non-obstructive nephrolithiasis. 3 Prior studies including 139 urine samples with 54 healthy controls validated the variation of KIT Stone-Score values between healthy non-stone formers and kidney stone patients and identified KIT's ability to detect kidney stone formers.…”

Targeted Urine Metabolomics for Monitoring Renal Allograft Injury and Immunosuppression in Pediatric Patients

“…These are first observations, should be consolidated with more integrative analysis of multi-omic datasets, and could be further aided by spatial metabolomics. Use of metabolomics for kidney disease outcomes generally could complement diagnostics made using other modalities, including gene expression, cell-free DNA, and proteomics [ 65 , 66 , 67 , 68 , 69 ].…”