Abstract
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. The study design benefits from longitudinally collected urine samples from an investigator-initiated, multicenter, prospective study, evaluating the efficacy of corticosteroids versus Rituximab for preventing progressive IgAN. A total of 131 urine samples were processed for this study; 64 urine samples were collected from 34 IgAN patients, and urine samples from 64 demographically matched healthy controls were also collected; multiple urinary biomarkers consisting of cell-free DNA, methylated cell-free DNA, DMAIMO, MAMIMO, total protein, clusterin, creatinine, and CXCL10 were measured by the microwell-based KIT Assay. An IgA risk score (KIT-IgA) was significantly higher in IgAN patients as compared to healthy control (87.76 vs. 14.03, p < 0.0001) and performed better than proteinuria in discriminating between the two groups. The KIT Assay biomarkers, measured on a spot random urine sample at study entry could distinguish patients likely to have progressive renal dysfunction a year later. These data support the pursuit of larger prospective studies to evaluate the predictive performance of the KIT-IgA score in both screening for non-invasive diagnosis of IgAN, and for predicting risk of progressive renal disease from IgA and utilizing the KIT score for potentially evaluating the efficacy of IgAN-targeted therapies.
Highlights
IgA nephropathy (IgAN) remains the most common type of primary chronic glomerulonephritis worldwide [1]
The Kidney Injury Test (KIT) Assay measures a panel of urinary biomarkers in a microwell-based format that were identified through a combination of proteomics, genomics, and metabolomics approaches [13,14,15] to be the most sensitive indicators of various etiologies of kidney injury and functional changes. In this investigator-initiated, multicenter, prospective study, we investigated the utility of the KIT Assay, a urine-based, microwell format assay for the detection of patients with IgAN who were treated with standard of care or with Rituximab
We used urine samples from IgA nephropathy (IgAN) patients to evaluate the predictive capacity of the KIT Assay biomarkers to discriminate IgAN from healthy controls as well as predict progression of renal functional decline
Summary
IgA nephropathy (IgAN) remains the most common type of primary chronic glomerulonephritis worldwide [1]. Its prevalence varies among different groups of people, where IgAN makes up about 20–40% of primary glomerular disease in Asia, and about 15–20% in Northern Europe [2]. The onset of IgAN may occur at any age, but the condition most frequently develops in patients in their second and third decades of life [3]. Many patients who present with mild symptoms will not require treatment, though they will be monitored for disease progression, but up to 40% of patients with IgAN will eventually develop end-stage renal disease [1]. One major issue in the treatment of IgAN is that there are few biomarkers that can predict progression of disease and monitor the efficacy of treatment [5]
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