Follistatin-related protein 3 for diagnosis and prognosis of renal injury and renal failure
Inventors
Anderberg, Joseph • McPherson, Paul • Gray, Jeff • Nakamura, Kevin • Kampf, James Patrick • Kwan, Thomas
Assignees
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Publication Number
US-11506672-B2
Publication Date
2022-11-22
Expiration Date
Abstract
The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more of Follistatin-related protein 3, Basigin, Cathepsin B, and Tenascin as diagnostic and prognostic bio-marker assays in renal injuries.
Core Innovation
The invention relates to detecting and using Follistatin-related protein 3 (FSTL3) in a body fluid sample from a subject to diagnose, prognose, and risk stratify acute kidney injury. The measured level is compared to a predetermined threshold value to determine whether the sample has an elevated level, and the level is used to determine an increased risk of future persistent RIFLE I (Injury) acute kidney injury or future persistent RIFLE F (Failure) acute kidney injury. Follistatin-related protein 3 comprises amino acid residues 27-263 of SEQ ID NO: 1 in the contexts where the biomarker is defined.
The disclosed approach includes immunoassay-based detection of FSTL3 in urine, blood, plasma, and/or serum using antibody binding and detection. The document describes persistent RIFLE criteria, including persistence duration and stage thresholds, and correlating marker levels with renal status outcomes across assessment time windows using ROC/AUC concepts and threshold-based interpretation. It also includes optional detection of additional kidney-injury-related biomarkers including Basigin, Cathepsin B, and Tenascin.
In addition to risk determination, the patent provides treating the subject with renal replacement therapy and/or withdrawing delivery of compounds known to be damaging to the kidney, and in some instances performing kidney transplantation. The invention further includes obtaining a body fluid sample from a human subject having persistent RIFLE I or persistent RIFLE F acute kidney injury and detecting Follistatin-related protein 3 by contacting the sample with an antibody that binds to the protein and detecting binding.
Claims Coverage
The independent claims cover three main inventive features centered on Follistatin-related protein 3, elevated-threshold risk determination, and RIFLE-based persistence criteria, with treatment and antibody-based detection tied to the claimed biomarker. The claims also include a time-bounded persistent RIFLE F embodiment within 48 hours and downstream renal replacement therapy, withdrawal of kidney-damaging compounds, and kidney transplantation.
Follistatin-related protein 3 assay for elevated threshold and risk of persistent RIFLE I or RIFLE F
Performing an assay method to detect a level of Follistatin-related protein 3 in a body fluid sample, wherein Follistatin-related protein 3 comprises amino acid residues 27-263 of SEQ ID NO: 1 and the sample has an elevated level compared to a predetermined threshold value; determining that the subject is at an increased risk of a future persistent RIFLE I (Injury) acute kidney injury or a future persistent RIFLE F (Failure) acute kidney injury based on the level of Follistatin-related protein 3.
Antibody-based detection of Follistatin-related protein 3
Obtaining a body fluid sample from a human subject having a persistent RIFLE I acute kidney injury or a persistent RIFLE F acute kidney injury; performing an assay method to detect a level of Follistatin-related protein 3, wherein the assay method comprises contacting the sample with an antibody that binds to the Follistatin-related protein 3, and detecting binding of the antibody to the Follistatin-related protein 3.
Timing- and persistence-defined increased risk for persistent RIFLE F within 48 hours
Determining that the subject is at an increased risk of developing a persistent RIFLE F (Failure) acute kidney injury within 48 hours of the time the sample is obtained, where persistence comprises a 72-hour period with a minimum RIFLE stage of RIFLE F, based on the level of Follistatin-related protein 3 in the sample; and treating the subject by administering renal replacement therapy and/or performing kidney transplantation and/or withdrawing delivery of compounds known to be damaging to the kidney if applicable.
The independent claims center on detecting Follistatin-related protein 3 comprising residues 27-263 of SEQ ID NO: 1 in a body fluid, interpreting an elevated level relative to a predetermined threshold to determine increased risk of persistent RIFLE-defined acute kidney injury states, and using that determination to drive treatment involving renal replacement therapy and/or withdrawing kidney-damaging compounds, with optional kidney transplantation in the persistent RIFLE F framework.
Stated Advantages
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