Biomarkers for Predicting Kidney and Glomerular Pathologies
AssigneeThe Ohio State University
InventorsBrad H. Rovin, Haikady N. Nagaraja, Xiaolan Zhang
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Abstract
Biomarkers for determining a kidney and glomerular pathologies and methods of using the same are described.
Claims91
A biomarker to predict one or more of lupus nephritis, renal fibrosis and chronic kidney disease, consisting two or more markers selected from:
- urine monocyte chemotactic protein-1 (uMCP-1), urine hepcidin (uHep), serum creatinine (Scr) and proteinura, expressed as a ratio of urine protein:creatine (uPCR).
A biomarker of interstitial inflammation in lupus nephritis (LN), comprising:
- urine monocyte chemotactic protein-1 (uMCP-1) and serum creatinine (Scr).
A biomarker of interstitial fibrosis in lupus nephritis (LN), comprising:
- urine hepcidin (uHep) and proteinura, expressed as a ratio of urine protein:creatine (uPCR).
A method for generating a result useful in diagnosing and non-invasively monitoring renal pathology using samples obtained from a mammalian subject, comprising:
- obtaining a dataset associated with the samples, wherein the dataset comprises protein expression levels for at least two markers selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR);
- and
- inputting the dataset into an analytical process that uses the data to generate a result useful in diagnosing and monitoring the renal pathology.
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A method for classifying a sample obtained from a mammalian subject, comprising:
- obtaining a dataset associated with the sample,
- wherein the dataset comprises expression levels for at least two markers selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR);
- inputting the dataset into an analytical process that uses the data to classify the sample, wherein the classification is selected from the group consisting of a lupus nephritis classification, a healthy classification, a renal-interstitial inflammation classification, a no renal-interstitial inflammation classification, a medication exposure classification, a no medication exposure classification;
- and
- classifying the sample according to the output of the process.
A method for classifying a sample obtained from a mammalian subject, comprising:
- obtaining a dataset associated with the sample,
- wherein the dataset comprises expression levels for at least two markers selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR);
- inputting the data into a predictive model that uses the data to classify the sample, wherein the classification is selected from the group consisting of:
- a renal-interstitial inflammation classification, a no renal-interstitial inflammation classification, wherein the predictive model has at least one quality metric of at least 0.7 for classification;
- and,
- classifying the sample according to the output of the predictive model.
A method of analyzing a subject sample for one or more subject-derived markers selected to identify at least a beginning of a renal-interstitial inflammation (INF) and/or tubulointerstitial inflammation (TI) episode in patients with lupus nephritis (LN), comprising:
- assaying the sample for the presence or amount of subject-derived markers related to a INT or TI episode, wherein at least two markers are selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR);
- and
- characterizing the subject's risk of having, or at risk for having, the INF and/or TI episode based upon the presence or amount of the markers.
A method for assigning a therapy regimen and/or assigning a prognosis to a subject diagnosed with or suspected of suffering from an interstitial inflammation episode, comprising:
- performing an assay on a sample obtained from the subject, wherein the assay provides one or more detectable signals related to the presence or amount of one or more subject-derived markers independently selected from the group consisting of markers related to kidney flare episodes, or markers related to the subject-derived markers;
- wherein at least two markers are selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR);
- and
- correlating the signal(s) obtained from the assay method to ruling in or out a therapy regimen for the subject and/or assigning a prognosis to the subject.
A method for assigning a therapy regimen and/or assigning a prognosis to a subject diagnosed with or suspected of suffering from interstitial fibrosis, comprising:
- performing an assay on a sample obtained from the subject, wherein the assay provides one or more detectable signals related to the presence or amount of one or more subject-derived markers independently selected from the group consisting of markers related to kidney flare episodes, or markers related to the subject-derived markers;
- wherein at least two markers are selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR);
- and
- correlating the signal(s) obtained from the assay method to ruling in or out a therapy regimen for the subject and/or assigning a prognosis to the subject.
A method for diagnosing a disease condition characterized by altered levels of at least two markers selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR);
- the method comprising:
- contacting a sample from a subject with an antibody or fragment thereof that specifically binds to one or more binding sites on the marker, and
- quantifying the marker levels in the sample;
- wherein the altered levels of the markers is indicative of the disease condition.
A kit for detecting a disease condition characterized by non-physiological levels of at least two markers are selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR);
- the kit comprising:
- an anti-marker antibody or fragment thereof that specifically binds to the marker, and a reagent that binds directly or indirectly to the antibody or fragment thereof.
A method for evaluating renal status in a subject, comprising:
- performing one or more assays configured to detect a kidney injury marker selected from at least two markers are selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR), on a body fluid sample obtained from the subject to provide one or more assay results;
- and
- correlating the assay result(s) to the renal status of the subject
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A method for evaluating renal status in a human test subject, the method comprising:
- a) measuring a level of expression in a sample of the test subject of at least two markers selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR), thereby obtaining a sample dataset;
- and
- b) applying a classifier to the sample dataset to thereby classify the test subject into a class representing human subjects having interstitial nephritis and/or interstitial fibrosis or a class representing human subjects not having interstitial nephritis and/or interstitial fibrosis,
- wherein the classifier is able to discriminate between human subjects having interstitial nephritis and/or interstitial fibrosis and human subjects not having interstitial nephritis and/or interstitial fibrosis, and
- wherein the classifier is derived from data representing a level of expression of at least two markers in samples of human subjects having interstitial nephritis and/or interstitial fibrosis and in samples of human subjects not having interstitial nephritis and/or interstitial fibrosis, thereby evaluating renal status in a human test subject.
The method of claim 62, wherein the applying the classifier to the sample dataset comprises using a computer programmed to apply the classifier to a dataset representing a level of expression of each marker in a sample of a human individual to thereby classify the human individual into the class representing human subjects having interstitial nephritis and/or interstitial fibrosis or the class representing human subjects not having interstitial nephritis and/or interstitial fibrosis.
A method for evaluating renal status in a human test subject, the method comprising:
- a) obtaining a sample dataset representing a level of expression in a sample of the test subject of subject of at least two markers selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR);
- and
- b) using a computer, applying a classifier to the sample dataset to thereby classify the test subject into a class representing human subjects having interstitial nephritis and/or interstitial fibrosis or a class representing human subjects not having interstitial nephritis or interstitial fibrosis,
- wherein the classifier is able to discriminate between human subjects having interstitial nephritis and/or interstitial fibrosis and human subjects not having interstitial nephritis and/or interstitial fibrosis,
- wherein the classifier is derived from data representing a level of expression of each marker of the marker set in samples of human subjects having interstitial nephritis and/or interstitial fibrosis and in samples of human subjects not having interstitial nephritis and/or interstitial fibrosis, and
- wherein the computer is programmed to apply the classifier to a dataset representing a level of expression of marker in a sample of a human individual to thereby classify the test individual into the class representing human subjects having interstitial nephritis fibrosis and/or interstitial fibrosis or the class representing human subjects not having interstitial nephritis and/or interstitial fibrosis, thereby evaluating renal status in a human test subject.
A method for profiling gene expression in a human test subject, the method comprising:
- using a computer, applying a classifier to a sample dataset representing a level of expression in a sample of the test subject of at least two markers selected from the group consisting of:
- urine monocyte chemotactic protein-1 (uMCP-1), serum creatinine (Src), hepcidin (uHep), and proteinura expressed as a ratio of urine protein:creatine (uPCR), to thereby classify the test subject into a class representing human subjects having interstitial nephritis and/or interstitial fibrosis or a class representing human subjects not having interstitial nephritis and/or interstitial fibrosis,
- wherein the classifier is able to discriminate between human subjects having interstitial nephritis and/or interstitial fibrosis and human subjects not having interstitial nephritis and/or interstitial fibrosis,
- wherein the classifier is derived from data representing a level of expression of each marker in samples of human subjects having interstitial nephritis and/or interstitial fibrosis and in samples of human subjects not having interstitial nephritis and/or interstitial fibrosis,
- and
- wherein the computer is programmed to apply the classifier to a dataset representing a level of expression of each marker in a sample of a human individual to thereby classify the human individual into the class representing human subjects having interstitial nephritis and/or interstitial fibrosis or the class representing human subjects not having interstitial nephritis and/or interstitial fibrosis, thereby evaluating renal status in a human test subject.
Dependencies are inferred from the claim text.