Devices for Detecting Renal Disorders
Devices for diagnosing, monitoring, or determining a renal disorder in a mammal are described. In particular, devices for diagnosing, monitoring, or determining a renal disorder using measured concentrations of a combination of three or more analytes in a test sample taken from the mammal are described.
1 . An assay device for diagnosing, monitoring, or determining a renal disorder in a mammal, the device comprising a panel of biomarkers for diagnosing, monitoring, or determining a renal disorder comprising six antibodies immobilized on a contact surface, wherein the antigenic determinants of the antibodies are analytes associated with renal disorder, wherein the analytes are selected from the group consisting of alpha-1 microglobulin, beta-2 microglobulin, cystatin C, KIM-1, THP, and TIMP-1.
2 . An assay device for diagnosing, monitoring, or determining a renal disorder in a mammal, the device comprising a panel of biomarkers for diagnosing, monitoring, or determining a renal disorder comprising three or more antibodies immobilized on a contact surface, wherein the antigenic determinants of the antibodies are analytes associated with renal disorder, wherein the analytes are selected from the group consisting of alpha-1 microglobulin, beta-2 microglobulin, calbindin, clusterin, CTGF, creatinine, cystatin C, GST-alpha, KIM-1, microalbumin, NGAL, osteopontin, THP, TIMP-1, TFF-3, VEGF, BLC, CD40, IGF BP2, MMP3, peptide YY, stem cell factor, TNF RII, AXL, Eotaxin 3, FABP, FGF basic, myoglobin, resistin, TRAIL R3, endothelin 1, NrCAM, Tenascin C, VCAM1, and cortisol.
3 . The assay device of claim 2 , wherein the three or more antibodies have antigenic determinants for analytes selected from the group consisting of alpha-1 microglobulin, beta-2 microglobulin, cystatin C, KIM-1, THP, and TIMP-1.
4 . The assay device of claim 2 , wherein the renal disorder comprises obstructive uropathy, and wherein the three or more antibodies have antigenic determinants for analytes selected from the group consisting of creatinine, THP, A1M, clusterin, NGAL, and osteopontin.
5 . The assay device of claim 2 , wherein the renal disorder comprises obstructive uropathy, wherein the panel of biomarkers has six antibodies having antigenic determinants for analytes selected from the group consisting of creatinine, THP, alpha-1 microglobulin, clusterin, NGAL, and osteopontin.
6 . The assay device of claim 2 , wherein the renal disorder comprises glomerulonephritis, and wherein the three or more antibodies have antigenic determinants for analytes selected from the group consisting of creatinine, KIM-1, TIMP-1, alpha-1 microglobulin, THP, and osteopontin.
7 . The assay device of claim 2 , wherein the renal disorder comprises glomerulonephritis, and wherein the panel of biomarkers has six antibodies having antigenic determinants for analytes selected from the group consisting of creatinine, KIM-1, TIMP-1, alpha-1 microglobulin, THP, and osteopontin.
8 . The assay device of claim 2 , wherein the renal disorder comprises kidney toxicity, and wherein the three or more antibodies have antigenic determinants for analytes selected from the group consisting of creatinine, KIM-1, THP, osteopontin, NGAL, and TIMP-1.
9 . The assay device of claim 2 , wherein the renal disorder comprises kidney toxicity, and wherein the panel of biomarkers has six antibodies having antigenic determinants for analytes selected from the group consisting of creatinine, KIM-1, THP, osteopontin, NGAL, and TIMP-1.
10 . The assay device of claim 2 , wherein the renal disorder comprises diabetic nephropathy, and wherein the three or more antibodies have antigenic determinants for analytes selected from the group consisting of microalbumin, alpha-1 microglobulin, NGAL, KIM-1, THP, and clusterin.
11 . The assay device of claim 2 , wherein the renal disorder comprises diabetic nephropathy, and wherein the panel of biomarkers has six antibodies having antigenic determinants for analytes selected from the group consisting of microalbumin, alpha-1 microglobulin, NGAL, KIM-1, THP, and clusterin.
12 . The assay device of claim 2 , wherein the renal disorder comprises kidney transplant rejection and chronic allograft nephropathy, and wherein the panel comprises three or more antibodies having antigenic determinants for analytes selected from the group consisting of BLC, CD40, IGF BP2, MMP3, peptide YY, stem cell factor, TNF RII, AXL, Eotaxin 3, FABP, FGF basic, myoglobin, resistin, TRAIL R3, endothelin 1, NrCAM, Tenascin C, VCAM1, and cortisol.
13 . The assay device of claim 2 , wherein the panel of biomarkers comprises ten or more antibodies having antigenic determinants for analytes selected from the group consisting of alpha-1 microglobulin, beta-2 microglobulin, calbindin, clusterin, CTGF, creatinine, cystatin C, GST-alpha, KIM-1, microalbumin, NGAL, osteopontin, THP, TIMP-1, TFF-3, and VEGF.
14 . The assay device of claim 2 , wherein the panel of biomarkers has sixteen antibodies having antigenic determinants for the analytes comprising alpha-1 microglobulin, beta-2 microglobulin, calbindin, clusterin, CTGF, creatinine, cystatin C, GST-alpha, KIM-1, microalbumin, NGAL, osteopontin, THP, TIMP-1, TFF-3, and VEGF.
15 . The assay device of claim 2 , wherein the contact surface comprises a substrate capable of immobilizing analytes captured by the antibodies.
16 . The assay device of claim 15 , wherein the substrate comprises a porous material selected from the group consisting of paper, nitrocellulose, cellulose, glass, glass fiber mesh, silica gel, synthetic resins, plastic strips, beads, the inner surface of a well, the surface of a microtitration tray, and combinations thereof.
17 . The assay device of claim 2 , further comprising a plurality of indicators, wherein one of the plurality of indicators is attached to one of the three or more antibodies
18 . The assay device of claim 2 , wherein the plurality of indicators comprises visual indicators and electrochemical indicators.
19 . The assay device of claim 18 , wherein the visual indicators are selected from the group consisting of nanoparticulate gold, polyurethane microspheres loaded with dye compounds, latex microspheres loaded with dye compounds, carbon black, fluorophores, phycoerythrin, radioactive isotopes, nanoparticles, and enzymes such as horseradish peroxidase or alkaline phosphatase that react with a chemical substrate to form a colored product.
20 . The assay device of claim 18 , wherein the electrochemical indicators are selected from the group consisting of ascorbate, vitamin E, glutathione, polyphenols, catechols, quercetin, phytoestrogens, penicillin, carbazole, murranes, phenols, carbonyls, benzoates, and trace metal ions such as nickel, copper, cadmium, iron, and mercury.
21 . The assay device of claim 2 , wherein the assay method comprises electrophoresis, mass spectrometry, protein microarrays, western blot, immunohistochemical staining, enzyme-linked immunosorbent assay methods, and particle-based capture-sandwich immunoassays.
22 . The assay device of claim 2 , wherein the renal disorder comprises glomerulonephritis, interstitial nephritis, tubular damage, vasculitis, glomerulosclerosis, acute renal failure, chronic renal failure, nephrosis, nephropathy, polycystic kidney disease, Bright's disease, renal transplant, chronic unilateral obstructive uropathy, chronic bilateral obstructive uropathy, acute unilateral obstructive uropathy, and acute bilateral obstructive uropathy.
23 . The assay device of claim 2 , wherein the renal disorder comprises renal damage caused by exposure to secondary agents and conditions including therapeutic drugs, recreational drugs, contrast agents, toxins, nephrolithiasis, ischemia, liver transplantation, heart transplantation, lung transplantation, and hypovolemia.
24 . The assay device of claim 2 , wherein the renal disorder comprises renal damage secondary to a primary disease state including diabetes, hypertension, autoimmune diseases including lupus, Wegener's granulomatosis, and Goodpasture syndrome, primary hyperoxaluria, kidney transplant rejection, sepsis, nephritis secondary to infection of the kidney, rhabdomyolysis, multiple myeloma, and prostate diseases.
25 . The assay device of claim 2 , wherein the mammal is selected from the group consisting of humans, apes, monkeys, rats, mice, dogs, cats, pigs, and livestock including cattle and oxen.
26 . An assay device for diagnosing, monitoring, or determining a renal disorder in a mammal, the device comprising:
a. three or more capture antibodies, wherein the antigenic determinants of the capture antibodies are analytes associated with a renal disorder, wherein the analytes are selected from the group consisting of alpha-1 microglobulin, beta-2 microglobulin, calbindin, clusterin, CTGF, creatinine, cystatin C, GST-alpha, KIM-1, microalbumin, NGAL, osteopontin, THP, TIMP-1, TFF-3, VEGF, BLC, CD40, IGF BP2, MMP3, peptide YY, stem cell factor, TNF RII, AXL, Eotaxin 3, FABP, FGF basic, myoglobin, resistin, TRAIL R3, endothelin 1, NrCAM, Tenascin C, VCAM1, and cortisol;
b. three or more capture agents comprising an antigenic moiety, wherein one of the capture agents is attached to each of the capture antibodies;
c. three or more detection antibodies, wherein the antigenic determinant of the detection antibodies is the antigenic moiety; and
d. three or more indicators, wherein each of the indicators is attached to one of the detection antibodies.
27 . The assay device of claim 26 , wherein the three or more capture antibodies have antigenic determinants for the analytes selected from the group consisting of alpha-1 microglobulin, beta-2 microglobulin, cystatin C, KIM-1, THP, and TIMP-1.
28 . The assay device of claim 26 , wherein the panel of biomarkers comprises six or more antibodies having antigenic determinants for the analytes comprising alpha-1 microglobulin, beta-2 microglobulin, cystatin C, KIM-1, THP, and TIMP-1.
29 . The assay device of claim 26 , wherein the panel of biomarkers comprises ten or more antibodies having antigenic determinants for the analytes comprising alpha-1 microglobulin, beta-2 microglobulin, calbindin, clusterin, CTGF, creatinine, cystatin C, GST-alpha, KIM-1, microalbumin, NGAL, osteopontin, THP, TIMP-1, TFF-3, and VEGF.
30 . The assay device of claim 26 , wherein the panel of biomarkers comprises sixteen or more antibodies having antigenic determinants for the analytes comprising alpha-1 microglobulin, beta-2 microglobulin, calbindin, clusterin, CTGF, creatinine, cystatin C, GST-alpha, KIM-1, microalbumin, NGAL, osteopontin, THP, TIMP-1, TFF-3, and VEGF.
31 . A kit for diagnosing, monitoring, or determining a renal disorder in a mammal, the kit comprising:
a. the assay device of claim 2 ; and
b. a collection apparatus suitable for collecting a sample of bodily fluid from the mammal.
32 . The kit of claim 31 , wherein the collection apparatus comprises urine sample cups, urethral catheters, swabs, hypodermic needles, thin needles, hollow needles, metabolic cages, and aspiration needles.
33 . A kit for diagnosing, monitoring, or determining a renal disorder in a mammal, the kit comprising:
a. the assay device of claim 26 ; and
b. a collection apparatus suitable for collecting a sample of bodily fluid from the mammal.
34 . The kit of claim 33 , wherein the collection apparatus comprises urine sample cups, urethral catheters, swabs, hypodermic needles, thin needles, hollow needles, metabolic cages, and aspiration needles.
35 . An assay device for diagnosing, monitoring, or determining a renal disorder in a mammal, the device comprising a panel of biomarkers having sixteen antibodies immobilized on a contact surface, wherein the antigenic determinants of the antibodies are analytes associated with renal disorder, wherein the analytes are selected from the group consisting of alpha-1-microglobulin, beta-2-microglobulin, calbindin, clusterin, CTGF, creatinine, cystatin C, GST-alpha, KIM-1, microalbumin, NGAL, osteopontin, THP, TIMP-1, TFF-3, and VEGF.
36 . A platform for diagnosing, monitoring, or determining a renal disorder in a mammal, the platform comprising at least 6 antibodies selected from the group consisting of alpha-1-microglobulin, beta-2-microglobulin, calbindin, clusterin, CTGF, creatinine, cystatin C, GST-alpha, KIM-1, microalbumin, NGAL, osteopontin, THP, TIMP-1, TFF-3, and VEGF.