Through the Looking Glass: Unraveling the Stage-Shift of Acute Rejection in Renal Allografts.

Sub-optimal sensitivity and specificity in current allograft monitoring methodologies underscore the need for more accurate and reflexive immunosurveillance to uncover the flux in alloimmunity between allograft health and the onset and progression of rejection. QSant-a urine based multi-analyte diagnostic test-was developed to profile renal transplant health and prognosticate injury, risk of evolution, and resolution of acute rejection. Q-Score-the composite score, across measurements of DNA, protein and metabolic biomarkers in the QSant assay-enables this risk prognostication.

Urinary Biomarkers for Kidney Allograft Injury.

The current standard of serum creatinine and biopsy to monitor allograft health has many limitations. The most significant drawback of the current standard is the lack of sensitivity and specificity to allograft injuries, which are diagnosed only after significant damage to the allograft. Thus, it is of critical need to identify a biomarker that is sensitive and specific to the early detection of allograft injuries.

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

The Kidney Injury Test (KIT) Stone-Score provides an objective measure of stone burden. Unlike urinary supersaturation the KIT Stone-Scores assess underlying stone disease rather than urinary solute composition. We report a case of a 43-year-old woman with no history of nephrolithiasis who underwent an elective, voluntary KIT assay and was diagnosed with a large staghorn renal stone after an unanticipated markedly elevated score.

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

Despite new advancements in surgical tools and therapies, exposure to immunosuppressive drugs related to non-immune and immune injuries can cause slow deterioration and premature failure of organ transplants. Diagnosis of these injuries by non-invasive urine monitoring would be a significant clinical advancement for patient management, especially in pediatric cohorts. We investigated the metabolomic profiles of biopsy matched urine samples from 310 unique kidney transplant recipients using gas chromatography-mass spectrometry (GC-MS).

Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients.

In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for the detection of biopsy-confirmed acute rejection in kidney transplants. Using a cohort of 223 distinct urine samples collected from three independent sites and from both adult and pediatric renal transplant patients, we examined the diagnostic utility of the urinary Q-Score for detection of acute rejection in renal allografts. Statistical models based upon the measurements of the six QSant biomarkers (cell-free DNA, methylated-cell-free DNA, clusterin, CXCL10, creatinine, and total protein) generated a renal transplant Q-Score that reliably differentiated stable allografts from acute rejections in both adult and pediatric renal transplant patients.

A urine score for noninvasive accurate diagnosis and prediction of kidney transplant rejection.

Accurate and noninvasive monitoring of renal allograft posttransplant is essential for early detection of acute rejection (AR) and to affect the long-term survival of the transplant. We present the development and validation of a noninvasive, spot urine-based diagnostic assay based on measurements of six urinary DNA, protein, and metabolic biomarkers. The performance of this assay for detecting kidney injury in both native kidneys and renal allografts is presented on a cohort of 601 distinct urine samples.

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

Objectives: To evaluate the utility of kidney injury test (KIT) assay urinary biomarkers to detect kidney stones and quantify stone burden.

Patients And Methods: 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.

Noninvasive Urinary Monitoring of Progression in IgA Nephropathy.

Standard methods for detecting and monitoring of IgA nephropathy (IgAN) have conventionally required kidney biopsies or suffer from poor sensitivity and specificity. The Kidney Injury Test (KIT) Assay of urinary biomarkers has previously been shown to distinguish between various kidney pathologies, including chronic kidney disease, nephrolithiasis, and transplant rejection. This validation study uses the KIT Assay to investigate the clinical utility of the non-invasive detection of IgAN and predicting the progression of renal damage over time.

A Novel Multi-Biomarker Assay for Non-Invasive Quantitative Monitoring of Kidney Injury.

The current standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early-stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples.

Cell-Free DNA and CXCL10 Derived from Bronchoalveolar Lavage Predict Lung Transplant Survival.

Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid.

Optimizing Detection of Kidney Transplant Injury by Assessment of Donor-Derived Cell-Free DNA via Massively Multiplex PCR.

Standard noninvasive methods for detecting renal allograft rejection and injury have poor sensitivity and specificity. Plasma donor-derived cell-free DNA (dd-cfDNA) has been reported to accurately detect allograft rejection and injury in transplant recipients and shown to discriminate rejection from stable organ function in kidney transplant recipients. This study used a novel single nucleotide polymorphism (SNP)-based massively multiplexed PCR (mmPCR) methodology to measure dd-cfDNA in various types of renal transplant recipients for the detection of allograft rejection/injury without prior knowledge of donor genotypes.

Transcriptional Perturbations in Graft Rejection.

Background: Understanding the regulatory interplay of relevant microRNAs (miRNAs) and messenger RNAs (mRNAs) in the rejecting allograft will result in a better understanding of the molecular pathophysiology of alloimmune injury.

Methods: One hundred sixty-seven allograft biopsies, with (n = 47) and without (n = 120) central histology for Banff scored acute rejection (AR), were transcriptionally profiled for mRNA and miRNA by whole genome microarrays and multiplexed microfluidic quantitative polymerase chain reaction, respectively. A customized database was curated (GO-Elite) and used to identify AR-specific dysregulated mRNAs and the role of perturbations of their relevant miRNAs targets during AR.