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Open AccessCommunication

Noninvasive Urinary Monitoring of Progression in IgA Nephropathy

1
Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA
2
KIT Bio, 665 3rd St, Suite 280, San Francisco, CA 94107, USA
3
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA
4
Division of Nephrology and Hypertension, Stanford University, Stanford, CA 94305, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4463; https://doi.org/10.3390/ijms20184463
Received: 26 July 2019 / Revised: 5 September 2019 / Accepted: 7 September 2019 / Published: 10 September 2019
(This article belongs to the Special Issue Kidney Inflammation, Injury and Regeneration)
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. View Full-Text
Keywords: IgA nephropathy; KIT assay; KIT-IgA score; noninvasive; diagnostics; prediction IgA nephropathy; KIT assay; KIT-IgA score; noninvasive; diagnostics; prediction
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MDPI and ACS Style

Yang, J.Y.C.; Sarwal, R.D.; Fervenza, F.C.; Sarwal, M.M.; Lafayette, R.A. Noninvasive Urinary Monitoring of Progression in IgA Nephropathy. Int. J. Mol. Sci. 2019, 20, 4463.

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