Methods for diagnosing acute kidney injury or renal failure
Inventors
Anderberg, Joseph • Gray, Jeff • McPherson, Paul • Nakamura, Kevin
Assignees
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Publication Number
US-11150250-B2
Publication Date
2021-10-19
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 markers selected from the group consisting of soluble p-selectin, protein NOV homolog, soluble epidermal growth factor receptor, netrin-4, haptoglobin, heat shock protein beta-1, alpha-1-antitrypsin, leukocyte elastase, soluble tumor necrosis factor receptor superfamily member 6, soluble tumor necrosis factor ligand superfamily member 6, soluble intercellular adhesion molecule 2, active caspase-3, and soluble platelet endothelial cell adhesion molecule as diagnostic and prognostic biomarkers in renal injuries.
Core Innovation
The invention concerns a diagnostic and prognostic framework for acute kidney injury and renal failure that uses kidney injury markers detected in body fluids, including urine and plasma, to evaluate renal injury states. It defines renal injury states such as injury, reduced renal function, and ARF/AKI, and links these states to renal injury criteria including RIFLE criteria (Risk, Injury, Failure; RIFLE stages).
The framework performs risk stratification, diagnosis, prognosis, and monitoring by comparing marker concentrations to predetermined threshold value(s), and it correlates assay results to an increased risk of future acute kidney injury meeting defined RIFLE stages. Marker detection is implemented using assay methods, preferably antibody-based immunoassays, that generate an assay result indicative of binding for a selected marker in a sample.
A specific embodiment emphasizes soluble tumor necrosis factor receptor superfamily member 6 (sTNFRSF6) detection in urine using an immunoassay with an antibody that specifically binds sTNFRSF6. The document includes example clinical study designs and data/ROC-AUC analyses to distinguish RIFLE stage 0 from stages R/I/F using sTNFRSF6 and related TNF superfamily biomarkers.
Claims Coverage
The independent claims cover two method families. Across these claims, the core inventive features are urine detection of soluble tumor necrosis factor receptor superfamily member 6 by antibody-based immunoassay, threshold-based correlation or increased-risk determination for future acute kidney injury meeting RIFLE I or F, and treatment with a compatible regimen including initiating renal replacement therapy and/or withdrawing delivery of compounds known to be damaging to the kidney.
Antibody-based detection of urinary sTNFRSF6
Detecting soluble tumor necrosis factor receptor superfamily member 6 in a urine sample with an antibody which specifically binds to the soluble tumor necrosis factor receptor superfamily member 6 using an immunoassay; and generating an assay result indicative of binding of the soluble tumor necrosis factor receptor superfamily member 6 to the antibody.
Threshold-based correlation to RIFLE I or F risk
Correlating the assay result to an increased risk of the subject developing a future acute kidney injury meeting the definition of RIFLE I or F when the assay result is above a predetermined threshold value.
Compatible regimen including renal replacement therapy and withdrawal of kidney-damaging compounds
Treating the subject having the increased risk of developing a future acute kidney injury meeting the definition of RIFLE I or F with a compatible treatment regimen comprising one or more of initiating renal replacement therapy and withdrawing delivery of compounds that are known to be damaging to the kidney.
Increased-risk determination from urinary sTNFRSF6 above a threshold
Determining the subject is at increased risk of a future acute kidney injury by performing an assay to detect soluble tumor necrosis factor receptor superfamily member 6 in a urine sample obtained from the subject, wherein the level of the soluble tumor necrosis factor receptor superfamily member 6 in the urine is above a predetermined threshold level.
The independent claims require urine detection of soluble tumor necrosis factor receptor superfamily member 6 via an antibody-based immunoassay, use a predetermined threshold to correlate to or determine increased risk of future acute kidney injury, and treat with a compatible regimen including initiating renal replacement therapy and/or withdrawing delivery of compounds known to be damaging to the kidney.
Stated Advantages
Enables evaluating a subject’s risk of future acute kidney injury using a kidney injury marker (sTNFRSF6) detected in urine by an immunoassay.
Supports correlating an assay result to increased risk of future acute kidney injury meeting RIFLE I or F.
Supports treating subjects with a compatible regimen including initiating renal replacement therapy and withdrawing delivery of compounds known to be damaging to the kidney based on the increased risk evaluation.
Documented Applications
Risk stratification, diagnosis, prognosis, and monitoring of acute kidney injury/renal failure using kidney injury markers detected in body fluids (including urine and plasma) by assay methods, preferably antibody-based immunoassays, with threshold comparisons and optional ROC/AUC evaluation.
Distinguishing RIFLE stage 0 from stages R/I/F using ROC/AUC analyses for sTNFRSF6 and related TNF superfamily biomarkers in example cohorts.
Example clinical study designs including contrast-induced nephropathy, cardiac surgery, and ICU cohorts.
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