US 12,584,924 B2Granted

Compositions and methods for diagnosing and treating chronic kidney disease

AssigneeSociete des Produits Nestle S.A.

InventorQinghong Li

Life of this patent

Estimating the term…

Abstract

The present invention relates to methods and compositions for diagnosing and enabling treatment of chronic kidney disease in a feline. In one embodiment, a method of diagnosing chronic kidney disease (CKD) in a feline can comprise measuring a normalized relative abundance of a first urine biomarker and determining if the feline has CKD, early-stage CKD, or late-stage CKD based on the normalized relative abundance.

Claims8

Dependent claims

A method of enabling treatment or slowing progression of chronic kidney disease in a feline, the method comprising:

(a) diagnosing chronic kidney disease (CKD) in the feline by (i) measuring a normalized relative abundance of a first urine biomarker selected from the urine biomarkers listed in Table 1 or Table 2:
TABLE 1
Diagnostic Range
(measured as normalized relative abundance)
Late-Stage
Indeterminate
Early-Stage
Urine Biomarker
CKD
Stage
Stage
Non-CKD
Sulfate
<−1.32
−1.319 to −0.58
−0.579 to 0.20
>0.21
N-acetylglucosamine/N-
<−1.41
−1.4 to −0.61
−0.60 to 0.20
>0.21
acetylgalactosamine
hydroxyasparagine
<−1.29
−1.28 to −0.55
−0.54 to 0.40
>0.41
serine
<−1.32
−1.31 to −0.74
−0.739 to 0.40
>0.41
urea
<−1.32
−1.31 to −0.73
−0.72 to 0.30
>0.31
1-methylnicotinamide
<−1.04
−1.03 to −0.71
−0.72 to 0.40
>0.41
fructose
<−1.06
−1.05 to −0.75
−0.74 to 0.40
>0.41
3-methylhistidine
—
—
−0.77 to 0.50
>0.51
pimelate
<−1.3
−1.29 to −0.64
−0.63 to 0.20
>0.21
4-acetylphenol sulfate
<−1.1
−1.09 to −0.68
−0.67 to 0.30
>0.31
N-acetyltryptophan
<−1.07
−1.06 to −0.75
−0.74 to 0.1
>0.11
stachydrine
<−1.5
−1.4 to −0.88
−0.87 to 0.30
>0.31
felinine
<−1.4
−1.39 to −0.64
−0.63 to 0.35
>0.36
N4-acetylcytidine
<−0.92
−0.91 to 0.00
0.01 to 0.30
>0.31
2-
<−0.57
−0.56 to −0.38
−0.37 to 0.32
>0.33
methylmalonylcarnitine
4-vinylphenol sulfate
<−1.35
−1.34 to −0.60
−0.59 to 0.40
>0.41
dimethylarginine
<−1.2
−1.1 to −0.74
−0.73 to 0.43
>0.44
(SDMA + ADMA)
N2,N2-
<−1.1
−1.1 to −0.65
−0.64 to 0.40
>0.41
dimethylguanine
N6-methyllysine
<−1.4
−1.3 to −0.62
−0.61 to 0.20
>0.21
equol sulfate
—
—
−0.72 to 0.30
>0.31
prolylglycine
<−1.2
−1.1 to −0.85
−0.84 to 0.20
>0.21
O-sulfo-L-tyrosine
<−1.5
−1.4 to −0.56
−0.55 to 0.50
>0.51
N6,N6-dimethyllysine
<−1.24
−1.23 to −1.17
−1.16 to 0.30
>0.31
dihydrocaffeate sulfate
<−0.89
−0.88 to −0.60
−0.59 to −0.36
>0.361
(2)
2,6-dihydroxybenzoic
<−0.86
−0.85 to −0.63
−0.62 to 0.25
>0.26
acid
picolinoylglycine
<−1.1
−1.0 to −0.79
−0.78 to 0.20
>0.21
vanillic acid glycine
<−0.77
−0.76 to −0.63
−0.62 to 0.20
>0.21
guanosine
<−1.1
−1.0 to −0.55
−0.54 to 0.43
>0.431
N-acetylalanine
<−1.22
−1.21 to −0.54
−0.53 to 0.0
>0.1
urate
<−1.34
−1.33 to −0.58
−0.57 to 0.40
>0.41
azelate
<−1.24
−1.23 to −0.91
−0.90 to 0.0
>0.01
arginine
<−1.34
−1.33 to −0.72
−0.71 to 0.49
>0.50
nicotinamide
<−1.4
−1.3 to −0.74
−0.73 to 0.20
>0.21
ornithine
<−1.32
−1.31 to −1.0
−0.99 to 0.30
>0.31
orotate
<−1.53
−1.52 to −0.50
−0.49 to 0.32
>0.33
trans-urocanate
<−1.44
−1.43 to −0.78
−0.77 to 0.35
>0.36
N-acetylglutamate
<−1.2
−1.1 to −0.87
−0.86 to 0.30
>0.31
ribitol
<−1.39
−1.38 to −0.27
−0.26 to 0.40
>0.41
indolelactate
<−1.13
−1.12 to −0.81
−0.80 to 0.20
>0.21
maleate
<−1.0
—
−0.99 to 0.10
>0.11
cysteine s-sulfate
<−0.88
−0.87 to −0.18
−0.17 to 0.10
>0.11
1-methylhistamine
<−0.79
−0.78 to −0.16
−0.15 to 0.33
>0.34
4-hydroxyhippurate
<−1.23
−1.22 to −0.90
−0.89 to 0.10
>0.11
isovalerylglycine
<−1.2
−1.1 to −0.94
−0.93 to 0.20
>0.21
7-methylguanine
<−1.3
−1.2 to −0.56
−0.55 to 0.30
>0.31
N6-acetyllysine
<−1.3
−1.2 to −0.60
−0.59 to 0.24
>0.25
pyrraline
<−0.49
−0.48 to −0.36
−0.35 to 0.20
>0.21
N6-
<−1.2
−1.1 to −0.83
−0.82 to 0.30
>0.31
carboxymethyllysine
cyclo(gly-pro)
<−1.17
—
−1.16 to 0.35
>0.36
2-hydroxyglutarate
<−1.21
−1.20 to −0.91
−0.90 to 0.0
>0.1
N-acetyl-cadaverine
<−1.3
−1.2 to −0.31
−0.30 to 0.34
>0.35
felinylglycine
<−1.1
−1.0 to −0.91
−0.90 to 0.10
>0.11
2-piperidinone
<−1.1
−1.0 to −0.66
−0.65 to 0.17
>0.18
3-acetylphenol sulfate
<−1.03
−1.02 to −1.01
−1.0 to 0.20
>0.21
methionine sulfone
<−0.72
−0.71 to −0.20
−0.19 to 0.35
>0.36
fructosyllysine
<−1.0
−0.99 to −0.86
−0.85 to 0.30
>0.31
4-vinylguaiacol sulfate
<−1.4
−1.3 to −0.60
−0.59 to 0.40
>0.41
4-methoxyphenol sulfate
—
—
0.61 to 0.45
>0.451
daidzein sulfate (2)
—
—
−0.82 to 0.30
>0.31
3-methoxycatechol
<−1.15
−1.14 to −0.67
−0.66 to 0.50
>0.51
sulfate (2)
N-acetylkynurenine (2)
<−1.1
−1.0 to −0.62
−0.61 to 0.10
>0.11
arabitol/xylitol
<−1.35
−1.34 to −0.75
−0.74 to 0.30
>0.31
indoleacetylglycine
<−1.2
−1.1 to −0.55
−0.54 to 0.24
>0.25
3-amino-2-piperidone
<−1.4
−1.3 to −1.2
−1.1 to 0.30
>0.31
5-hydroxy-2-
<−1.1
−1.0 to −0.47
−0.46 to 0.02
>0.03
methylpyridine sulfate
4-vinylcatechol sulfate
<−1.0
−0.99 to −0.60
−0.59 to 0.40
>0.41
oxindolylalanine
<−1.0
—
−0.99 to 0.10
>0.11
N1-methyladenosine
<−1.21
−1.20 to −0.49
−0.48 to 0.35
>0.36
choline
<−1.0
−0.99 to −0.86
−0.85 to 0.20
>0.21
3-phosphoglycerate
<−0.96
−0.95 to −0.83
−0.82 to 0.40
>0.41
N(′1)-acetylspermidine
<−1.1
−1.0 to −0.82
−0.81 to 0.39
>0.40
ethylmalonate
<−1.15
−1.14 to −0.66
−0.65 to 0.30
>0.31
guanidinoacetate
<−1.39
−1.38 to −0.87
−0.86 to 0.65
>0.64
allantoin
<−1.34
−1.33 to −0.68
−0.67 to 0.36
>0.37
TABLE 2
Diagnostic Range
(measured as normalized relative abundance)
Early-Stage
Indeterminate
Late-Stage
Urine Biomarker
Non-CKD
Stage
Stage
CKD
1-methylguanidine
<0.72
0.72 to 1.41
—
>1.41
4-ureidobutyrate
<0.77
0.77 to 1.38
—
>1.38
1-methyl-5-imidazolelactate
<0.78
0.78 to 1.39
—
>1.39
scyllo-inositol
<0.79
0.79 to 1.28
—
>1.28
fucitol
<0.8
0.8 to 1.29
—
>1.29
N-acetyl-1-methylhistidine
<0.82
0.82 to 1.43
—
>1.43
arachidonate (20:4n6)
<0.83
0.83 to 1.47
—
>1.47
N-formylanthranilic acid
<0.83
0.83 to 1.36
—
>1.36
N-acetyl-isoputreanine
<0.85
0.85 to 1.34
—
>1.34
3-methylglutarylcarnitine (2)
<0.86
0.86 to 1.35
—
>1.35
2-O-methylascorbic acid
<0.87
0.87 to 1.42
—
>1.42
furaneol sulfate
<0.87
0.87 to 1.32
—
>1.32
glucuronate
<0.88
0.88 to 1.49
—
>1.49
citrate
<0.88
0.88 to 1.34
—
>1.34
benzoate
<0.88
0.88 to 1.31
—
>1.31
indolin-2-one
<0.88
0.88 to 1.28
—
>1.28
nicotinamide N-oxide
<0.89
0.89 to 1.47
—
>1.47
carboxyethyl-GABA
<0.9
0.9 to 1.44
—
>1.44
lyxonate
<0.9
0.9 to 1.34
—
>1.34
glucose
<0.9
0.9 to 1.69
—
>1.69
dimethylguanidino valeric acid
<0.91
0.91 to 1.43
—
>1.43
(DMGV)
isocitrate
<0.91
0.91 to 1.42
—
>1.42
allantoic acid
<0.91
0.91 to 1.91
—
>1.91
1-methyladenine
<0.92
0.92 to 1.46
—
>1.46
N-acetyltaurine
<0.92
0.92 to 1.44
—
>1.44
trimethylamine N-oxide
<0.92
0.92 to 1.41
—
>1.41
4-hydroxyphenylacetoylcarnitine
<0.92
0.92 to 1.38
—
>1.38
1-methylhypoxanthine
<0.92
0.92 to 1.34
—
>1.34
N-acetylneuraminate
<0.92
0.92 to 1.92
—
>1.92
malonylcarnitine
<0.93
0.93 to 1.5
—
>1.5
nicotinamide riboside
<0.93
0.93 to 1.47
—
>1.47
pimeloylcarnitine/3-
<0.93
0.93 to 1.35
—
>1.35
methyladipoylcarnitine (C7-DC)
N-glycolylneuraminate
<0.93
0.93 to 1.6
—
>1.6
azelaoyltaurine
<0.93
0.93 to 1.89
—
>1.89
3-carboxyadipate
<0.94
0.94 to 1.37
—
>1.37
dimethyl sulfone
<0.94
0.94 to 1.31
—
>1.31
tartronate (hydroxymalonate)
<0.95
0.95 to 1.44
—
>1.44
ascorbic acid 3-sulfate
<0.95
0.95 to 1.38
—
>1.38
malate
<0.95
0.95 to 1.35
—
>1.35
isovalerylcarnitine (C5)
<0.95
0.95 to 1.31
—
>1.31
glutarylcarnitine (C5-DC)
<0.96
0.96 to 1.64
—
>1.64
guanidinosuccinate
<0.97
0.97 to 1.41
—
>1.41
3′-sialyllactose
<0.97
0.97 to 1.35
—
>1.35
3-ureidopropionate
<0.97
0.97 to 1.68
—
>1.68
N6-succinyladenosine
<0.98
0.98 to 1.38
—
>1.38
C-glycosyltryptophan
<0.98
0.98 to 1.67
—
>1.67
isobutyrylcarnitine (C4)
<0.99
0.99 to 1.37
—
>1.37
N1-methylinosine
<0.99
0.99 to 1.63
—
>1.63
cysteinylglycine
<1.01
1.01 to 1.43
—
>1.43
5,6-dihydrouridine
<1.01
1.01 to 1.84
—
>1.84
pseudouridine
<1.01
1.01 to 1.83
—
>1.83
5-methylthioribose
<1.01
1.01 to 1.53
—
>1.53
3,4-methylenevaleroylglycine
<1.02
1.02 to 1.42
—
>1.42
cysteine-glutathione disulfide
<1.02
1.02 to 1.52
—
>1.52
N-methylpipecolate
<1.03
1.03 to 1.43
—
>1.43
7-methylurate
<1.03
1.03 to 1.32
—
>1.32
ribonate
<1.03
1.03 to 1.55
—
>1.55
N1-Methyl-2-pyridone-5-
<1.04
1.04 to 1.66
—
>1.66
carboxamide
1-methyl-4-imidazoleacetate
<1.05
1.05 to 1.56
—
>1.56
S-methylcysteine
<1.06
1.06 to 1.38
—
>1.38
creatinine
<1.07
1.07 to 2.03
—
>2.03
N-acetylserine
<1.1
1.1 to 1.54
—
>1.54
pyridoxate
<1.11
1.11 to 1.38
—
>1.38
gulonate
<1.11
1.11 to 1.47
—
>1.47
N-carbamoylputrescine
<1.14
1.14 to 1.65
—
>1.65
norvaline
<1.17
1.17 to 1.42
—
>1.42
tryptophan
>1.05
1.05 to 0.73
—
<0.73
phenyllactate (PLA)
>1.08
1.08 to 0.71
—
<0.71
dihydroorotate
>1.1
1.1 to 0.67
—
<0.67
N-acetylglycine
>1.11
1.11 to 0.64
—
<0.64
beta-guanidinopropanoate
>1.11
1.11 to 0.64
—
<0.64
5-oxoproline
>1.12
1.12 to 0.62
—
<0.62
5-hydroxylysine
>1.13
1.13 to 0.61
—
<0.61
cholate
>1.14
1.14 to 0.62
—
<0.62
azelate (C9-DC)
>1.16
1.16 to 0.61
—
<0.61
N-acetylvaline
>1.22
1.22 to 0.77
—
<0.77
glycylvaline
>1.23
1.23 to 0.77
—
<0.77
heptanoylglutamine
>1.23
1.23 to 0.76
—
<0.76
isovalerate (i5:0)
>1.26
1.26 to 0.75
—
<0.75
butyrylputrescine/isobutyrylputrescine
>1.28
1.28 to 0.77
—
<0.77
homoarginine
>1.28
1.28 to 0.77
—
<0.77
homostachydrine
>1.28
1.28 to 0.75
—
<0.75
N6-methyladenosine
>1.28
1.28 to 0.75
—
<0.75
3-methoxytyramine
>1.29
1.29 to 0.91
—
<0.91
N-acetylhistamine
>1.29
1.29 to 0.79
—
<0.79
ferulylglycine (1)
>1.29
1.29 to 0.78
—
<0.78
S-methylcysteine sulfoxide
>1.3
1.3 to 0.84
—
<0.84
cyclo(pro-tyr)
>1.3
1.3 to 0.75
—
<0.75
N-lactoyl leucine
>1.31
1.31 to 0.74
—
<0.74
histamine
>1.31
1.31 to 0.72
—
<0.72
gamma-glutamylglycine
>1.31
1.31 to 0.73
—
<0.73
putrescine
>1.32
1.32 to 0.78
—
<0.78
alanyllysine
>1.32
1.32 to 0.74
—
<0.74
chenodeoxycholic acid sulfate (2)
>1.32
1.32 to 0.74
—
<0.74
N2,N2-dimethylguanosine
>1.33
1.33 to 0.77
—
<0.77
S-adenosylmethioninamine
>1.33
1.33 to 0.76
—
<0.76
betaine
>1.33
1.33 to 0.75
—
<0.75
dihydrobiopterin
>1.33
1.33 to 0.73
—
<0.73
methylmalonate (MMA)
>1.34
1.34 to 0.89
—
<0.89
2-methylbutyrylglycine
>1.34
1.34 to 0.75
—
<0.75
glycerophosphoglycerol
>1.35
1.35 to 0.79
—
<0.79
cadaverine
>1.36
1.36 to 0.77
—
<0.77
glucuronide of C10H18O2 (11)
>1.41
1.41 to 0.77
—
<0.77
and
(ii) determining that the feline has CKD if the normalized relative abundance of the first urine biomarker has a value outside the range under the non-CKD column, determining that the feline has early-stage chronic kidney disease if the normalized relative abundance of the first urine biomarker has a value in the range under the early-stage CKD column, or determining that the feline has late-stage CKD if the normalized relative abundance of the first urine biomarker has a value in the range under the late-stage CKD column;
and
(b) recommending a composition for the feline, wherein the composition treats or slows the progression of CKD in the feline, wherein the composition includes a combination of glycine, methionine, cysteine and glutamine.

921 more elements

A method of enabling treatment or slowing progression of chronic kidney disease in a feline, the method comprising:

(a) diagnosing chronic kidney disease (CKD) in the feline by (i) measuring a normalized relative abundance of a first urine biomarker selected from the urine biomarkers listed in Table 1 or Table 2:
TABLE 1
Diagnostic Range
(measured as normalized relative abundance)
Late-Stage
Indeterminate
Early-Stage
Non-
Urine Biomarker
CKD
Stage
Stage
CKD
Sulfate
<−1.32
−1.319 to −0.58
−0.579 to 0.20
>0.21
N-acetylglucosamine/
<−1.41
−1.4 to −0.61
−0.60 to 0.20
>0.21
N-acetylgalactosamine
hydroxyasparagine
<−1.29
−1.28 to −0.55
−0.54 to 0.40
>0.41
serine
<−1.32
−1.31 to −0.74
−0.739 to 0.40
>0.41
urea
<−1.32
−1.31 to −0.73
−0.72 to 0.30
>0.31
1-methylnicotinamide
<−1.04
−1.03 to −0.71
−0.72 to 0.40
>0.41
fructose
<−1.06
−1.05 to −0.75
−0.74 to 0.40
>0.41
3-methylhistidine
—
—
−0.77 to 0.50
>0.51
pimelate
<−1.3
−1.29 to −0.64
−0.63 to 0.20
>0.21
4-acetylphenol sulfate
<−1.1
−1.09 to −0.68
−0.67 to 0.30
>0.31
N-acetyltryptophan
<−1.07
−1.06 to −0.75
−0.74 to 0.1
>0.11
stachydrine
<−1.5
−1.4 to −0.88
−0.87 to 0.30
>0.31
felinine
<−1.4
−1.39 to −0.64
−0.63 to 0.35
>0.36
N4-acetylcytidine
<−0.92
−0.91 to 0.00
0.01 to 0.30
>0.31
2-methylmalonyl-carnitine
<−0.57
−0.56 to −0.38
−0.37 to 0.32
>0.33
4-vinylphenol sulfate
<−1.35
−1.34 to −0.60
−0.59 to 0.40
>0.41
dimethylarginine
<−1.2
−1.1 to −0.74
−0.73 to 0.43
>0.44
(SDMA + ADMA)
N2,N2-dimethylguanine
<−1.1
−1.1 to −0.65
−0.64 to 0.40
>0.41
N6-methyllysine
<−1.4
−1.3 to −0.62
−0.61 to 0.20
>0.21
equol sulfate
—
—
−0.72 to 0.30
>0.31
prolylglycine
<−1.2
−1.1 to −0.85
−0.84 to 0.20
>0.21
O-sulfo-L-tyrosine
<−1.5
−1.4 to −0.56
−0.55 to 0.50
>0.51
N6,N6-dimethyllysine
<−1.24
−1.23 to −1.17
−1.16 to 0.30
>0.31
dihydrocaffeate sulfate (2)
<−0.89
−0.88 to −0.60
−0.59 to −0.36
>0.361
2,6-dihydroxybenzoic acid
<−0.86
−0.85 to −0.63
−0.62 to 0.25
>0.26
picolinoylglycine
<−1.1
−1.0 to −0.79
−0.78 to 0.20
>0.21
vanillic acid glycine
<−0.77
−0.76 to −0.63
−0.62 to 0.20
>0.21
guanosine
<−1.1
−1.0 to −0.55
−0.54 to 0.43
>0.431
N-acetylalanine
<−1.22
−1.21 to −0.54
−0.53 to 0.0
>0.1
urate
<−1.34
−1.33 to −0.58
−0.57 to 0.40
>0.41
azelate
<−1.24
−1.23 to −0.91
−0.90 to 0.0
>0.01
arginine
<−1.34
−1.33 to −0.72
−0.71 to 0.49
>0.50
nicotinamide
<−1.4
−1.3 to −0.74
−0.73 to 0.20
>0.21
ornithine
<−1.32
−1.31 to −1.0
−0.99 to 0.30
>0.31
orotate
<−1.53
−1.52 to −0.50
−0.49 to 0.32
>0.33
trans-urocanate
<−1.44
−1.43 to −0.78
−0.77 to 0.35
>0.36
N-acetylglutamate
<−1.2
−1.1 to −0.87
−0.86 to 0.30
>0.31
ribitol
<−1.39
−1.38 to −0.27
−0.26 to 0.40
>0.41
indolelactate
<−1.13
−1.12 to −0.81
−0.80 to 0.20
>0.21
maleate
<−1.0
—
−0.99 to 0.10
>0.11
cysteine s-sulfate
<−0.88
−0.87 to −0.18
−0.17 to 0.10
>0.11
1-methylhistamine
<−0.79
−0.78 to −0.16
−0.15 to 0.33
>0.34
4-hydroxyhippurate
<−1.23
−1.22 to −0.90
−0.89 to 0.10
>0.11
isovalerylglycine
<−1.2
−1.1 to −0.94
−0.93 to 0.20
>0.21
7-methylguanine
<−1.3
−1.2 to −0.56
−0.55 to 0.30
>0.31
N6-acetyllysine
<−1.3
−1.2 to −0.60
−0.59 to 0.24
>0.25
pyrraline
<−0.49
−0.48 to −0.36
−0.35 to 0.20
>0.21
N6-carboxymethyllysine
<−1.2
−1.1 to −0.83
−0.82 to 0.30
>0.31
cyclo(gly-pro)
<−1.17
—
−1.16 to 0.35
>0.36
2-hydroxyglutarate
<−1.21
−1.20 to −0.91
−0.90 to 0.0
>0.1
N-acetyl-cadaverine
<−1.3
−1.2 to −0.31
−0.30 to 0.34
>0.35
felinylglycine
<−1.1
−1.0 to −0.91
−0.90 to 0.10
>0.11
2-piperidinone
<−1.1
−1.0 to −0.66
−0.65 to 0.17
>0.18
3-acetylphenol sulfate
<−1.03
−1.02 to −1.01
−1.0 to 0.20
>0.21
methionine sulfone
<−0.72
−0.71 to −0.20
−0.19 to 0.35
>0.36
fructosyllysine
<−1.0
−0.99 to −0.86
−0.85 to 0.30
>0.31
4-vinylguaiacol sulfate
<−1.4
−1.3 to −0.60
−0.59 to 0.40
>0.41
4-methoxyphenol sulfate
—
—
0.61 to 0.45
>0.451
daidzein sulfate (2)
—
—
−0.82 to 0.30
>0.31
3-methoxycatechol sulfate (2)
<−1.15
−1.14 to −0.67
−0.66 to 0.50
>0.51
N-acetylkynurenine (2)
<−1.1
−1.0 to −0.62
−0.61 to 0.10
>0.11
arabitol/xylitol
<−1.35
−1.34 to −0.75
−0.74 to 0.30
>0.31
indoleacetylglycine
<−1.2
−1.1 to −0.55
−0.54 to 0.24
>0.25
3-amino-2-piperidone
<−1.4
−1.3 to −1.2
−1.1 to 0.30
>0.31
5-hydroxy-2-methylpyridine
<−1.1
−1.0 to −0.47
−0.46 to 0.02
>0.03
sulfate
4-vinylcatechol sulfate
<−1.0
−0.99 to −0.60
−0.59 to 0.40
>0.41
oxindolylalanine
<−1.0
—
−0.99 to 0.10
>0.11
N1-methyladenosine
<−1.21
−1.20 to −0.49
−0.48 to 0.35
>0.36
choline
<−1.0
−0.99 to −0.86
−0.85 to 0.20
>0.21
3-phosphoglycerate
<−0.96
−0.95 to −0.83
−0.82 to 0.40
>0.41
N(′1)-acetylspermidine
<−1.1
−1.0 to −0.82
−0.81 to 0.39
>0.40
ethylmalonate
<−1.15
−1.14 to −0.66
−0.65 to 0.30
>0.31
guanidinoacetate
<−1.39
−1.38 to −0.87
−0.86 to 0.65
>0.64
allantoin
<−1.34
−1.33 to −0.68
−0.67 to 0.36
>0.37
TABLE 2
Diagnostic Range
(measured as normalized
relative abundance)
Indeter-
Late-
Non-
Early-Stage
minate
Stage
Urine Biomarker
CKD
Stage
Stage
CKD
1-methylguanidine
<0.72
0.72 to 1.41
—
>1.41
4-ureidobutyrate
<0.77
0.77 to 1.38
—
>1.38
1-methyl-5-
<0.78
0.78 to 1.39
—
>1.39
imidazolelactate
scyllo-inositol
<0.79
0.79 to 1.28
—
>1.28
fucitol
<0.8
0.8 to 1.29
—
>1.29
N-acetyl-1-
<0.82
0.82 to 1.43
—
>1.43
methylhistidine
arachidonate (20:4n6)
<0.83
0.83 to 1.47
—
>1.47
N-formylanthranilic acid
<0.83
0.83 to 1.36
—
>1.36
N-acetyl-isoputreanine
<0.85
0.85 to 1.34
—
>1.34
3-methylglutarylcarnitine
<0.86
0.86 to 1.35
—
>1.35
(2)
2-O-methylascorbic acid
<0.87
0.87 to 1.42
—
>1.42
furaneol sulfate
<0.87
0.87 to 1.32
—
>1.32
glucuronate
<0.88
0.88 to 1.49
—
>1.49
citrate
<0.88
0.88 to 1.34
—
>1.34
benzoate
<0.88
0.88 to 1.31
—
>1.31
indolin-2-one
<0.88
0.88 to 1.28
—
>1.28
nicotinamide N-oxide
<0.89
0.89 to 1.47
—
>1.47
carboxyethyl-GABA
<0.9
0.9 to 1.44
—
>1.44
lyxonate
<0.9
0.9 to 1.34
—
>1.34
glucose
<0.9
0.9 to 1.69
—
>1.69
dimethylguanidino
<0.91
0.91 to 1.43
—
>1.43
valeric acid (DMGV)
isocitrate
<0.91
0.91 to 1.42
—
>1.42
allantoic acid
<0.91
0.91 to 1.91
—
>1.91
1-methyladenine
<0.92
0.92 to 1.46
—
>1.46
N-acetyltaurine
<0.92
0.92 to 1.44
—
>1.44
trimethylamine N-oxide
<0.92
0.92 to 1.41
—
>1.41
4-hydroxyphenyl-
<0.92
0.92 to 1.38
—
>1.38
acetoylcarnitine
1 -methylhypoxanthine
<0.92
0.92 to 1.34
—
>1.34
N-acetylneuraminate
<0.92
0.92 to 1.92
—
>1.92
malonylcarnitine
<0.93
0.93 to 1.5
—
>1.5
nicotinamide riboside
<0.93
0.93 to 1.47
—
>1.47
pimeloylcarnitine/3-
<0.93
0.93 to 1.35
—
>1.35
methyladipoylcarnitine
(C7-DC)
N-glycolylneuraminate
<0.93
0.93 to 1.6
—
>1.6
azelaoyltaurine
<0.93
0.93 to 1.89
—
>1.89
3-carboxyadipate
<0.94
0.94 to 1.37
—
>1.37
dimethyl sulfone
<0.94
0.94 to 1.31
—
>1.31
tartronate
<0.95
0.95 to 1.44
—
>1.44
(hydroxymalonate)
ascorbic acid 3-sulfate
<0.95
0.95 to 1.38
—
>1.38
malate
<0.95
0.95 to 1.35
—
>1.35
isovalerylcarnitine (C5)
<0.95
0.95 to 1.31
—
>1.31
glutarylcarnitine
<0.96
0.96 to 1.64
—
>1.64
(C5-DC)
guanidinosuccinate
<0.97
0.97 to 1.41
—
>1.41
3′-sialyllactose
<0.97
0.97 to 1.35
—
>1.35
3-ureidopropionate
<0.97
0.97 to 1.68
—
>1.68
N6-succinyladenosine
<0.98
0.98 to 1.38
—
>1.38
C-glycosyltryptophan
<0.98
0.98 to 1.67
—
>1.67
isobutyrylcarnitine (C4)
<0.99
0.99 to 1.37
—
>1.37
N1-methylinosine
<0.99
0.99 to 1.63
—
>1.63
cysteinylglycine
<1.01
1.01 to 1.43
—
>1.43
5,6-dihydrouridine
<1.01
1.01 to 1.84
—
>1.84
pseudouridine
<1.01
1.01 to 1.83
—
>1.83
5-methylthioribose
<1.01
1.01 to 1.53
—
>1.53
3,4-
<1.02
1.02 to 1.42
—
>1.42
methylenevaleroylglycine
cysteine-glutathione
<1.02
1.02 to 1.52
—
>1.52
disulfide
N-methylpipecolate
<1.03
1.03 to 1.43
—
>1.43
7-methylurate
<1.03
1.03 to 1.32
—
>1.32
ribonate
<1.03
1.03 to 1.55
—
>1.55
N1-Methyl-2-pyridone-
<1.04
1.04 to 1.66
—
>1.66
5-carboxamide
1-methyl-4-
<1.05
1.05 to 1.56
—
>1.56
imidazoleacetate
S-methylcysteine
<1.06
1.06 to 1.38
—
>1.38
creatinine
<1.07
1.07 to 2.03
—
>2.03
N-acetylserine
<1.1
1.1 to 1.54
—
>1.54
pyridoxate
<1.11
1.11 to 1.38
—
>1.38
gulonate
<1.11
1.11 to 1.47
—
>1.47
N-carbamoylputrescine
<1.14
1.14 to 1.65
—
>1.65
norvaline
<1.17
1.17 to 1.42
—
>1.42
tryptophan
>1.05
1.05 to 0.73
—
<0.73
phenyllactate (PLA)
>1.08
1.08 to 0.71
—
<0.71
dihydroorotate
>1.1
1.1 to 0.67
—
<0.67
N-acetylglycine
>1.11
1.11 to 0.64
—
<0.64
beta-
>1.11
1.11 to 0.64
—
<0.64
guanidinopropanoate
5-oxoproline
>1.12
1.12 to 0.62
—
<0.62
5-hydroxylysine
>1.13
1.13 to 0.61
—
<0.61
cholate
>1.14
1.14 to 0.62
—
<0.62
azelate (C9-DC)
>1.16
1.16 to 0.61
—
<0.61
N-acetylvaline
>1.22
1.22 to 0.77
—
<0.77
glycylvaline
>1.23
1.23 to 0.77
—
<0.77
heptanoylglutamine
>1.23
1.23 to 0.76
—
<0.76
isovalerate (15:0)
>1.26
1.26 to 0.75
—
<0.75
butyrylputrescine/
>1.28
1.28 to 0.77
—
<0.77
isobutyrylputrescine
homoarginine
>1.28
1.28 to 0.77
—
<0.77
homostachydrine
>1.28
1.28 to 0.75
—
<0.75
N6-methyladenosine
>1.28
1.28 to 0.75
—
<0.75
3-methoxytyramine
>1.29
1.29 to 0.91
—
<0.91
N-acetylhistamine
>1.29
1.29 to 0.79
—
<0.79
ferulylglycine (1)
>1.29
1.29 to 0.78
—
<0.78
S-methylcysteine
>1.3
1.3 to 0.84
—
<0.84
sulfoxide
cyclo(pro-tyr)
>1.3
1.3 to 0.75
—
<0.75
N-lactoyl leucine
>1.31
1.31 to 0.74
—
<0.74
histamine
>1.31
1.31 to 0.72
—
<0.72
gamma-glutamylglycine
>1.31
1.31 to 0.73
—
<0.73
putrescine
>1.32
1.32 to 0.78
—
<0.78
alanyllysine
>1.32
1.32 to 0.74
—
<0.74
chenodeoxycholic acid
>1.32
1.32 to 0.74
—
<0.74
sulfate (2)
N2,N2-
>1.33
1.33 to 0.77
—
<0.77
dimethylguanosine
S-
>1.33
1.33 to 0.76
—
<0.76
adenosylmethioninamine
betaine
>1.33
1.33 to 0.75
—
<0.75
dihydrobiopterin
>1.33
1.33 to 0.73
—
<0.73
methylmalonate (MMA)
>1.34
1.34 to 0.89
—
<0.89
2-methylbutyrylglycine
>1.34
1.34 to 0.75
—
<0.75
glycerophosphoglycerol
>1.35
1.35 to 0.79
—
<0.79
cadaverine
>1.36
1.36 to 0.77
—
<0.77
glucuronide of
>1.41
1.41 to 0.77
—
<0.77
C10H18O2 (11)
and
(ii) determining that the feline has CKD if the normalized relative abundance of the first urine biomarker has a value outside the range under the non-CKD column, determining that the feline has early-stage chronic kidney disease if the normalized relative abundance of the first urine biomarker has a value in the range under the early-stage CKD column, or determining that the feline has late-stage CKD if the normalized relative abundance of the first urine biomarker has a value in the range under the late-stage CKD column;
and
(b) recommending a composition for the feline, wherein the composition treats or slows the progression of CKD in the feline, wherein the composition comprises arginine, eicosapentaenoic acid, docosahexaenoic acid, vitamin E, and B vitamins.

937 more elements

A method of enabling treatment or slowing progression of chronic kidney disease in a feline, the method comprising:

(a) diagnosing chronic kidney disease (CKD) in the feline by (i) measuring a normalized relative abundance of a first urine biomarker selected from the urine biomarkers listed in Table 1 or Table 2:
TABLE 1
Diagnostic Range
(measured as normalized relative abundance)
Late-
Stage
Indeterminate
Early-Stage
Non-
Urine Biomarker
CKD
Stage
Stage
CKD
Sulfate
<−1.32
−1.319 to −0.58
−0.579 to 0.20
>0.21
N-acetylglucosamine/
<−1.41
−1.4 to −0.61
−0.60 to 0.20
>0.21
N-acetylgalactosamine
hydroxyasparagine
<−1.29
−1.28 to −0.55
−0.54 to 0.40
>0.41
serine
<−1.32
−1.31 to −0.74
−0.739 to 0.40
>0.41
urea
<−1.32
−1.31 to −0.73
−0.72 to 0.30
>0.31
1-methylnicotinamide
<−1.04
−1.03 to −0.71
−0.72 to 0.40
>0.41
fructose
<−1.06
−1.05 to −0.75
−0.74 to 0.40
>0.41
3-methylhistidine
—
—
−0.77 to 0.50
>0.51
pimelate
<−1.3
−1.29 to −0.64
−0.63 to 0.20
>0.21
4-acetylphenol sulfate
<−1.1
−1.09 to −0.68
−0.67 to 0.30
>0.31
N-acetyltryptophan
<−1.07
−1.06 to −0.75
−0.74 to 0.1
>0.11
stachydrine
<−1.5
−1.4 to −0.88
−0.87 to 0.30
>0.31
felinine
<−1.4
−1.39 to −0.64
−0.63 to 0.35
>0.36
N4-acetylcytidine
<−0.92
−0.91 to 0.00
−0.01 to 0.30
>0.31
2-methylmalonyl-carnitine
<−0.57
−0.56 to −0.38
−0.37 to 0.32
>0.33
4-vinylphenol sulfate
<−1.35
−1.34 to −0.60
−0.59 to 0.40
>0.41
dimethylarginine
<−1.2
−1.1 to −0.74
−0.73 to 0.43
>0.44
(SDMA + ADMA)
N2,N2-dimethylguanine
<−1.1
−1.1 to −0.65
−0.64 to 0.40
>0.41
N6-methyllysine
<−1.4
−1.3 to −0.62
−0.61 to 0.20
>0.21
equol sulfate
—
—
−0.72 to 0.30
>0.31
prolylglycine
<−1.2
−1.1 to −0.85
−0.84 to 0.20
>0.21
O-sulfo-L-tyrosine
<−1.5
−1.4 to −0.56
−0.55 to 0.50
>0.51
N6,N6-dimethyllysine
<−1.24
−1.23 to −1.17
−1.16 to 0.30
>0.31
dihydrocaffeate sulfate (2)
<−0.89
−0.88 to −0.60
−0.59 to −0.36
>0.361
2,6-dihydroxybenzoic acid
<−0.86
−0.85 to −0.63
−0.62 to 0.25
>0.26
picolinoylglycine
<−1.1
−1.0 to −0.79
−0.78 to 0.20
>0.21
vanillic acid glycine
<−0.77
−0.76 to −0.63
−0.62 to 0.20
>0.21
guanosine
<−1.1
−1.0 to −0.55
−0.54 to 0.43
>0.431
N-acetylalanine
<−1.22
−1.21 to −0.54
−0.53 to 0.0
>0.1
urate
<−1.34
−1.33 to −0.58
−0.57 to 0.40
>0.41
azelate
<−1.24
−1.23 to −0.91
−0.90 to 0.0
>0.01
arginine
<−1.34
−1.33 to −0.72
−0.71 to 0.49
>0.50
nicotinamide
<−1.4
−1.3 to −0.74
−0.73 to 0.20
>0.21
ornithine
<−1.32
−1.31 to −1.0
−0.99 to 0.30
>0.31
orotate
<−1.53
−1.52 to −0.50
−0.49 to 0.32
>0.33
trans-urocanate
<−1.44
−1.43 to −0.78
−0.77 to 0.35
>0.36
N-acetylglutamate
<−1.2
−1.1 to −0.87
−0.86 to 0.30
>0.31
ribitol
<−1.39
−1.38 to −0.27
−0.26 to 0.40
>0.41
indolelactate
<−1.13
−1.12 to −0.81
−0.80 to 0.20
>0.21
maleate
<−1.0
—
−0.99 to 0.10
>0.11
cysteine s-sulfate
<−0.88
−0.87 to −0.18
−0.17 to 0.10
>0.11
1-methylhistamine
<−0.79
−0.78 to −0.16
−0.15 to 0.33
>0.34
4-hydroxyhippurate
<−1.23
−1.22 to −0.90
−0.89 to 0.10
>0.11
isovalerylglycine
<−1.2
−1.1 to −0.94
−0.93 to 0.20
>0.21
7-methylguanine
<−1.3
−1.2 to −0.56
−0.55 to 0.30
>0.31
N6-acetyllysine
<−1.3
−1.2 to −0.60
−0.59 to 0.24
>0.25
pyrraline
<−0.49
−0.48 to −0.36
−0.35 to 0.20
>0.21
N6-carboxymethyllysine
<−1.2
−1.1 to −0.83
−0.82 to 0.30
>0.31
cyclo(gly-pro)
<−1.17
—
−1.16 to 0.35
>0.36
2-hydroxyglutarate
<−1.21
−1.20 to −0.91
−0.90 to 0.0
>0.1
N-acetyl-cadaverine
<−1.3
−1.2 to −0.31
−0.30 to 0.34
>0.35
felinylglycine
<−1.1
−1.0 to −0.91
−0.90 to 0.10
>0.11
2-piperidinone
<−1.1
−1.0 to −0.66
−0.65 to 0.17
>0.18
3-acetylphenol sulfate
<−1.03
−1.02 to −1.01
−1.0 to 0.20
>0.21
methionine sulfone
<−0.72
−0.71 to −0.20
−0.19 to 0.35
>0.36
fructosyllysine
<−1.0
−0.99 to −0.86
−0.85 to 0.30
>0.31
4-vinylguaiacol sulfate
<−1.4
−1.3 to −0.60
−0.59 to 0.40
>0.41
4-methoxyphenol sulfate
—
—
−0.61 to 0.45
>0.451
daidzein sulfate (2)
—
—
−0.82 to 0.30
>0.31
3-methoxycatechol sulfate (2)
<−1.15
−1.14 to −0.67
−0.66 to 0.50
>0.51
N-acetylkynurenine (2)
<−1.1
−1.0 to −0.62
−0.61 to 0.10
>0.11
arabitol/xylitol
<−1.35
−1.34 to −0.75
−0.74 to 0.30
>0.31
indoleacetylglycine
<−1.2
−1.1 to −0.55
−0.54 to 0.24
>0.25
3-amino-2-piperidone
<−1.4
−1.3 to −1.2
−1.1 to 0.30
>0.31
5-hydroxy-2-methylpyridine
<−1.1
−1.0 to −0.47
−0.46 to 0.02
>0.03
sulfate
4-vinylcatechol sulfate
<−1.0
−0.99 to −0.60
−0.59 to 0.40
>0.41
oxindolylalanine
<−1.0
—
−0.99 to 0.10
>0.11
N1-methyladenosine
<−1.21
−1.20 to −0.49
−0.48 to 0.35
>0.36
choline
<−1.0
−0.99 to −0.86
−0.85 to 0.20
>0.21
3-phosphoglycerate
<−0.96
−0.95 to −0.83
−0.82 to 0.40
>0.41
N(′1)-acetylspermidine
<−1.1
−1.0 to −0.82
−0.81 to 0.39
>0.40
ethylmalonate
<−1.15
−1.14 to −0.66
−0.65 to 0.30
>0.31
guanidinoacetate
<−1.39
−1.38 to −0.87
−0.86 to 0.65
>0.64
allantoin
<−1.34
−1.33 to −0.68
−0.67 to 0.36
>0.37
TABLE 2
Diagnostic Range
(measured as normalized relative abundance)
Non-
Early-Stage
Indeterminate
Late-Stage
Urine Biomarker
CKD
Stage
Stage
CKD
1-methylguanidine
<0.72
0.72 to 1.41
—
>1.41
4-ureidobutyrate
<0.77
0.77 to 1.38
—
>1.38
1-methyl-5-imidazolelactate
<0.78
0.78 to 1.39
—
>1.39
scyllo-inositol
<0.79
0.79 to 1.28
—
>1.28
fucitol
<0.8
0.8 to 1.29
—
>1.29
N-acetyl-1-methylhistidine
<0.82
0.82 to 1.43
—
>1.43
arachidonate (20:4n6)
<0.83
0.83 to 1.47
—
>1.47
N-formylanthranilic acid
<0.83
0.83 to 1.36
—
>1.36
N-acetyl-isoputreanine
<0.85
0.85 to 1.34
—
>1.34
3-methylglutarylcarnitine (2)
<0.86
0.86 to 1.35
—
>1.35
2-O-methylascorbic acid
<0.87
0.87 to 1.42
—
>1.42
furaneol sulfate
<0.87
0.87 to 1.32
—
>1.32
glucuronate
<0.88
0.88 to 1.49
—
>1.49
citrate
<0.88
0.88 to 1.34
—
>1.34
benzoate
<0.88
0.88 to 1.31
—
>1.31
indolin-2-one
<0.88
0.88 to 1.28
—
>1.28
nicotinamide N-oxide
<0.89
0.89 to 1.47
—
>1.47
carboxyethyl-GABA
<0.9
0.9 to 1.44
—
>1.44
lyxonate
<0.9
0.9 to 1.34
—
>1.34
glucose
<0.9
0.9 to 1.69
—
>1.69
dimethylguanidino valeric acid
<0.91
0.91 to 1.43
—
>1.43
(DMGV)
isocitrate
<0.91
0.91 to 1.42
—
>1.42
allantoic acid
<0.91
0.91 to 1.91
—
>1.91
1-methyladenine
<0.92
0.92 to 1.46
—
>1.46
N-acetyltaurine
<0.92
0.92 to 1.44
—
>1.44
trimethylamine N-oxide
<0.92
0.92 to 1.41
—
>1.41
4-hydroxyphenylacetoylcarnitine
<0.92
0.92 to 1.38
—
>1.38
1-methylhypoxanthine
<0.92
0.92 to 1.34
—
>1.34
N-acetylneuraminate
<0.92
0.92 to 1.92
—
>1.92
malonylcarnitine
<0.93
0.93 to 1.5
—
>1.5
nicotinamide riboside
<0.93
0.93 to 1.47
—
>1.47
pimeloylcarnitine/3-
<0.93
0.93 to 1.35
—
>1.35
methyladipoylcarnitine (C7-DC)
N-glycolylneuraminate
<0.93
0.93 to 1.6
—
>1.6
azelaoyltaurine
<0.93
0.93 to 1.89
—
>1.89
3-carboxyadipate
<0.94
0.94 to 1.37
—
>1.37
dimethyl sulfone
<0.94
0.94 to 1.31
—
>1.31
tartronate (hydroxymalonate)
<0.95
0.95 to 1.44
—
>1.44
ascorbic acid 3-sulfate
<0.95
0.95 to 1.38
—
>1.38
malate
<0.95
0.95 to 1.35
—
>1.35
isovalerylcarnitine (C5)
<0.95
0.95 to 1.31
—
>1.31
glutarylcarnitine (C5-DC)
<0.96
0.96 to 1.64
—
>1.64
guanidinosuccinate
<0.97
0.97 to 1.41
—
>1.41
3′-sialyllactose
<0.97
0.97 to 1.35
—
>1.35
3-ureidopropionate
<0.97
0.97 to 1.68
—
>1.68
N6-succinyladenosine
<0.98
0.98 to 1.38
—
>1.38
C-glycosyltryptophan
<0.98
0.98 to 1.67
—
>1.67
isobutyrylcarnitine (C4)
<0.99
0.99 to 1.37
—
>1.37
N1-methylinosine
<0.99
0.99 to 1.63
—
>1.63
cysteinylglycine
<1.01
1.01 to 1.43
—
>1.43
5,6-dihydrouridine
<1.01
1.01 to 1.84
—
>1.84
pseudouridine
<1.01
1.01 to 1.83
—
>1.83
5-methylthioribose
<1.01
1.01 to 1.53
—
>1.53
3,4-methylenevaleroylglycine
<1.02
1.02 to 1.42
—
>1.42
cysteine-glutathione disulfide
<1.02
1.02 to 1.52
—
>1.52
N-methylpipecolate
<1.03
1.03 to 1.43
—
>1.43
7-methylurate
<1.03
1.03 to 1.32
—
>1.32
ribonate
<1.03
1.03 to 1.55
—
>1.55
N1-Methyl-2-pyridone-5-
<1.04
1.04 to 1.66
—
>1.66
carboxamide
1-methyl-4-imidazoleacetate
<1.05
1.05 to 1.56
—
>1.56
S-methylcysteine
<1.06
1.06 to 1.38
—
>1.38
creatinine
<1.07
1.07 to 2.03
—
>2.03
N-acetylserine
<1.1
1.1 to 1.54
—
>1.54
pyridoxate
<1.11
1.11 to 1.38
—
>1.38
gulonate
<1.11
1.11 to 1.47
—
>1.47
N-carbamoylputrescine
<1.14
1.14 to 1.65
—
>1.65
norvaline
<1.17
1.17 to 1.42
—
>1.42
tryptophan
>1.05
1.05 to 0.73
—
<0.73
phenyllactate (PLA)
>1.08
1.08 to 0.71
—
<0.71
dihydroorotate
>1.1
1.1 to 0.67
—
<0.67
N-acetylglycine
>1.11
1.11 to 0.64
—
<0.64
beta-guanidinopropanoate
>1.11
1.11 to 0.64
—
<0.64
5-oxoproline
>1.12
1.12 to 0.62
—
<0.62
5-hydroxylysine
>1.13
1.13 to 0.61
—
<0.61
cholate
>1.14
1.14 to 0.62
—
<0.62
azelate (C9-DC)
>1.16
1.16 to 0.61
—
<0.61
N-acetylvaline
>1.22
1.22 to 0.77
—
<0.77
glycylvaline
>1.23
1.23 to 0.77
—
<0.77
heptanoylglutamine
>1.23
1.23 to 0.76
—
<0.76
isovalerate (i5:0)
>1.26
1.26 to 0.75
—
<0.75
butyrylputrescine/isobutyrylputrescine
>1.28
1.28 to 0.77
—
<0.77
homoarginine
>1.28
1.28 to 0.77
—
<0.77
homostachydrine
>1.28
1.28 to 0.75
—
<0.75
N6-methyladenosine
>1.28
1.28 to 0.75
—
<0.75
3-methoxytyramine
>1.29
1.29 to 0.91
—
<0.91
N-acetylhistamine
>1.29
1.29 to 0.79
—
<0.79
ferulylglycine (1)
>1.29
1.29 to 0.78
—
<0.78
S-methylcysteine sulfoxide
>1.3
1.3 to 0.84
—
<0.84
cyclo(pro-tyr)
>1.3
1.3 to 0.75
—
<0.75
N-lactoyl leucine
>1.31
1.31 to 0.74
—
<0.74
histamine
>1.31
1.31 to 0.72
—
<0.72
gamma-glutamylglycine
>1.31
1.31 to 0.73
—
<0.73
putrescine
>1.32
1.32 to 0.78
—
<0.78
alanyllysine
>1.32
1.32 to 0.74
—
<0.74
chenodeoxycholic acid sulfate (2)
>1.32
1.32 to 0.74
—
<0.74
N2,N2-dimethylguanosine
>1.33
1.33 to 0.77
—
<0.77
S-adenosylmethioninamine
>1.33
1.33 to 0.76
—
<0.76
betaine
>1.33
1.33 to 0.75
—
<0.75
dihydrobiopterin
>1.33
1.33 to 0.73
—
<0.73
methylmalonate (MMA)
>1.34
1.34 to 0.89
—
<0.89
2-methylbutyrylglycine
>1.34
1.34 to 0.75
—
<0.75
glycerophosphoglycerol
>1.35
1.35 to 0.79
—
<0.79
cadaverine
>1.36
1.36 to 0.77
—
<0.77
glucuronide of C10H18O2 (11)
>1.41
1.41 to 0.77
—
<0.77
and
(ii) determining that the feline has CKD if the normalized relative abundance of the first urine biomarker has a value outside the range under the non-CKD column, determining that the feline has early-stage chronic kidney disease if the normalized relative abundance of the first urine biomarker has a value in the range under the early-stage CKD column, or determining that the feline has late-stage CKD if the normalized relative abundance of the first urine biomarker has a value in the range under the late-stage CKD column;
and
(b) recommending a composition for the feline, wherein the composition treats or slows the progression of CKD in the feline, wherein the composition contains less than 1% of potassium and contains less than 1% of phosphorous compounds and phosphate compounds.

918 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/085,795Filed 21 Dec 2022 · us provisional application
Priority: 27 Dec 2021
Published: US 2023/0204604 A129 Jun 2023
Granted: 24 Mar 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

G01N 33/50
Biological material, e.g. blood, urine ; Haemocytometers: chemical analysis of biological material, e.g. blood, urine; Testing involving…
G01N 33/6893
Involving proteins, peptides or amino acids: related to diseases not provided for elsewhere
G01N 2570/00
Omics
G01N 2800/347
Genitourinary disorders: renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis;…

Family

Application63/293,861Us provisional application · filed 27 Dec 2021
US 2023/0204604 A1Pre-grant publication · published 29 Jun 2023
US 12,584,924 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Citations

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Abstract

A method of enabling treatment or slowing progression of chronic kidney disease in a feline, the method comprising:

(a) diagnosing chronic kidney disease (CKD) in the feline by (i) measuring a normalized relative abundance of a first urine biomarker selected from the urine biomarkers listed in Table 1 or Table 2:
TABLE 1
Diagnostic Range
(measured as normalized relative abundance)
Late-Stage
Indeterminate
Early-Stage
Urine Biomarker
CKD
Stage
Stage
Non-CKD
Sulfate
<−1.32
−1.319 to −0.58
−0.579 to 0.20
>0.21
N-acetylglucosamine/N-
<−1.41
−1.4 to −0.61
−0.60 to 0.20
>0.21
acetylgalactosamine
hydroxyasparagine
<−1.29
−1.28 to −0.55
−0.54 to 0.40
>0.41
serine
<−1.32
−1.31 to −0.74
−0.739 to 0.40
>0.41
urea
<−1.32
−1.31 to −0.73
−0.72 to 0.30
>0.31
1-methylnicotinamide
<−1.04
−1.03 to −0.71
−0.72 to 0.40
>0.41
fructose
<−1.06
−1.05 to −0.75
−0.74 to 0.40
>0.41
3-methylhistidine
—
—
−0.77 to 0.50
>0.51
pimelate
<−1.3
−1.29 to −0.64
−0.63 to 0.20
>0.21
4-acetylphenol sulfate
<−1.1
−1.09 to −0.68
−0.67 to 0.30
>0.31
N-acetyltryptophan
<−1.07
−1.06 to −0.75
−0.74 to 0.1
>0.11
stachydrine
<−1.5
−1.4 to −0.88
−0.87 to 0.30
>0.31
felinine
<−1.4
−1.39 to −0.64
−0.63 to 0.35
>0.36
N4-acetylcytidine
<−0.92
−0.91 to 0.00
0.01 to 0.30
>0.31
2-
<−0.57
−0.56 to −0.38
−0.37 to 0.32
>0.33
methylmalonylcarnitine
4-vinylphenol sulfate
<−1.35
−1.34 to −0.60
−0.59 to 0.40
>0.41
dimethylarginine
<−1.2
−1.1 to −0.74
−0.73 to 0.43
>0.44
(SDMA + ADMA)
N2,N2-
<−1.1
−1.1 to −0.65
−0.64 to 0.40
>0.41
dimethylguanine
N6-methyllysine
<−1.4
−1.3 to −0.62
−0.61 to 0.20
>0.21
equol sulfate
—
—
−0.72 to 0.30
>0.31
prolylglycine
<−1.2
−1.1 to −0.85
−0.84 to 0.20
>0.21
O-sulfo-L-tyrosine
<−1.5
−1.4 to −0.56
−0.55 to 0.50
>0.51
N6,N6-dimethyllysine
<−1.24
−1.23 to −1.17
−1.16 to 0.30
>0.31
dihydrocaffeate sulfate
<−0.89
−0.88 to −0.60
−0.59 to −0.36
>0.361
(2)
2,6-dihydroxybenzoic
<−0.86
−0.85 to −0.63
−0.62 to 0.25
>0.26
acid
picolinoylglycine
<−1.1
−1.0 to −0.79
−0.78 to 0.20
>0.21
vanillic acid glycine
<−0.77
−0.76 to −0.63
−0.62 to 0.20
>0.21
guanosine
<−1.1
−1.0 to −0.55
−0.54 to 0.43
>0.431
N-acetylalanine
<−1.22
−1.21 to −0.54
−0.53 to 0.0
>0.1
urate
<−1.34
−1.33 to −0.58
−0.57 to 0.40
>0.41
azelate
<−1.24
−1.23 to −0.91
−0.90 to 0.0
>0.01
arginine
<−1.34
−1.33 to −0.72
−0.71 to 0.49
>0.50
nicotinamide
<−1.4
−1.3 to −0.74
−0.73 to 0.20
>0.21
ornithine
<−1.32
−1.31 to −1.0
−0.99 to 0.30
>0.31
orotate
<−1.53
−1.52 to −0.50
−0.49 to 0.32
>0.33
trans-urocanate
<−1.44
−1.43 to −0.78
−0.77 to 0.35
>0.36
N-acetylglutamate
<−1.2
−1.1 to −0.87
−0.86 to 0.30
>0.31
ribitol
<−1.39
−1.38 to −0.27
−0.26 to 0.40
>0.41
indolelactate
<−1.13
−1.12 to −0.81
−0.80 to 0.20
>0.21
maleate
<−1.0
—
−0.99 to 0.10
>0.11
cysteine s-sulfate
<−0.88
−0.87 to −0.18
−0.17 to 0.10
>0.11
1-methylhistamine
<−0.79
−0.78 to −0.16
−0.15 to 0.33
>0.34
4-hydroxyhippurate
<−1.23
−1.22 to −0.90
−0.89 to 0.10
>0.11
isovalerylglycine
<−1.2
−1.1 to −0.94
−0.93 to 0.20
>0.21
7-methylguanine
<−1.3
−1.2 to −0.56
−0.55 to 0.30
>0.31
N6-acetyllysine
<−1.3
−1.2 to −0.60
−0.59 to 0.24
>0.25
pyrraline
<−0.49
−0.48 to −0.36
−0.35 to 0.20
>0.21
N6-
<−1.2
−1.1 to −0.83
−0.82 to 0.30
>0.31
carboxymethyllysine
cyclo(gly-pro)
<−1.17
—
−1.16 to 0.35
>0.36
2-hydroxyglutarate
<−1.21
−1.20 to −0.91
−0.90 to 0.0
>0.1
N-acetyl-cadaverine
<−1.3
−1.2 to −0.31
−0.30 to 0.34
>0.35
felinylglycine
<−1.1
−1.0 to −0.91
−0.90 to 0.10
>0.11
2-piperidinone
<−1.1
−1.0 to −0.66
−0.65 to 0.17
>0.18
3-acetylphenol sulfate
<−1.03
−1.02 to −1.01
−1.0 to 0.20
>0.21
methionine sulfone
<−0.72
−0.71 to −0.20
−0.19 to 0.35
>0.36
fructosyllysine
<−1.0
−0.99 to −0.86
−0.85 to 0.30
>0.31
4-vinylguaiacol sulfate
<−1.4
−1.3 to −0.60
−0.59 to 0.40
>0.41
4-methoxyphenol sulfate
—
—
0.61 to 0.45
>0.451
daidzein sulfate (2)
—
—
−0.82 to 0.30
>0.31
3-methoxycatechol
<−1.15
−1.14 to −0.67
−0.66 to 0.50
>0.51
sulfate (2)
N-acetylkynurenine (2)
<−1.1
−1.0 to −0.62
−0.61 to 0.10
>0.11
arabitol/xylitol
<−1.35
−1.34 to −0.75
−0.74 to 0.30
>0.31
indoleacetylglycine
<−1.2
−1.1 to −0.55
−0.54 to 0.24
>0.25
3-amino-2-piperidone
<−1.4
−1.3 to −1.2
−1.1 to 0.30
>0.31
5-hydroxy-2-
<−1.1
−1.0 to −0.47
−0.46 to 0.02
>0.03
methylpyridine sulfate
4-vinylcatechol sulfate
<−1.0
−0.99 to −0.60
−0.59 to 0.40
>0.41
oxindolylalanine
<−1.0
—
−0.99 to 0.10
>0.11
N1-methyladenosine
<−1.21
−1.20 to −0.49
−0.48 to 0.35
>0.36
choline
<−1.0
−0.99 to −0.86
−0.85 to 0.20
>0.21
3-phosphoglycerate
<−0.96
−0.95 to −0.83
−0.82 to 0.40
>0.41
N(′1)-acetylspermidine
<−1.1
−1.0 to −0.82
−0.81 to 0.39
>0.40
ethylmalonate
<−1.15
−1.14 to −0.66
−0.65 to 0.30
>0.31
guanidinoacetate
<−1.39
−1.38 to −0.87
−0.86 to 0.65
>0.64
allantoin
<−1.34
−1.33 to −0.68
−0.67 to 0.36
>0.37
TABLE 2
Diagnostic Range
(measured as normalized relative abundance)
Early-Stage
Indeterminate
Late-Stage
Urine Biomarker
Non-CKD
Stage
Stage
CKD
1-methylguanidine
<0.72
0.72 to 1.41
—
>1.41
4-ureidobutyrate
<0.77
0.77 to 1.38
—
>1.38
1-methyl-5-imidazolelactate
<0.78
0.78 to 1.39
—
>1.39
scyllo-inositol
<0.79
0.79 to 1.28
—
>1.28
fucitol
<0.8
0.8 to 1.29
—
>1.29
N-acetyl-1-methylhistidine
<0.82
0.82 to 1.43
—
>1.43
arachidonate (20:4n6)
<0.83
0.83 to 1.47
—
>1.47
N-formylanthranilic acid
<0.83
0.83 to 1.36
—
>1.36
N-acetyl-isoputreanine
<0.85
0.85 to 1.34
—
>1.34
3-methylglutarylcarnitine (2)
<0.86
0.86 to 1.35
—
>1.35
2-O-methylascorbic acid
<0.87
0.87 to 1.42
—
>1.42
furaneol sulfate
<0.87
0.87 to 1.32
—
>1.32
glucuronate
<0.88
0.88 to 1.49
—
>1.49
citrate
<0.88
0.88 to 1.34
—
>1.34
benzoate
<0.88
0.88 to 1.31
—
>1.31
indolin-2-one
<0.88
0.88 to 1.28
—
>1.28
nicotinamide N-oxide
<0.89
0.89 to 1.47
—
>1.47
carboxyethyl-GABA
<0.9
0.9 to 1.44
—
>1.44
lyxonate
<0.9
0.9 to 1.34
—
>1.34
glucose
<0.9
0.9 to 1.69
—
>1.69
dimethylguanidino valeric acid
<0.91
0.91 to 1.43
—
>1.43
(DMGV)
isocitrate
<0.91
0.91 to 1.42
—
>1.42
allantoic acid
<0.91
0.91 to 1.91
—
>1.91
1-methyladenine
<0.92
0.92 to 1.46
—
>1.46
N-acetyltaurine
<0.92
0.92 to 1.44
—
>1.44
trimethylamine N-oxide
<0.92
0.92 to 1.41
—
>1.41
4-hydroxyphenylacetoylcarnitine
<0.92
0.92 to 1.38
—
>1.38
1-methylhypoxanthine
<0.92
0.92 to 1.34
—
>1.34
N-acetylneuraminate
<0.92
0.92 to 1.92
—
>1.92
malonylcarnitine
<0.93
0.93 to 1.5
—
>1.5
nicotinamide riboside
<0.93
0.93 to 1.47
—
>1.47
pimeloylcarnitine/3-
<0.93
0.93 to 1.35
—
>1.35
methyladipoylcarnitine (C7-DC)
N-glycolylneuraminate
<0.93
0.93 to 1.6
—
>1.6
azelaoyltaurine
<0.93
0.93 to 1.89
—
>1.89
3-carboxyadipate
<0.94
0.94 to 1.37
—
>1.37
dimethyl sulfone
<0.94
0.94 to 1.31
—
>1.31
tartronate (hydroxymalonate)
<0.95
0.95 to 1.44
—
>1.44
ascorbic acid 3-sulfate
<0.95
0.95 to 1.38
—
>1.38
malate
<0.95
0.95 to 1.35
—
>1.35
isovalerylcarnitine (C5)
<0.95
0.95 to 1.31
—
>1.31
glutarylcarnitine (C5-DC)
<0.96
0.96 to 1.64
—
>1.64
guanidinosuccinate
<0.97
0.97 to 1.41
—
>1.41
3′-sialyllactose
<0.97
0.97 to 1.35
—
>1.35
3-ureidopropionate
<0.97
0.97 to 1.68
—
>1.68
N6-succinyladenosine
<0.98
0.98 to 1.38
—
>1.38
C-glycosyltryptophan
<0.98
0.98 to 1.67
—
>1.67
isobutyrylcarnitine (C4)
<0.99
0.99 to 1.37
—
>1.37
N1-methylinosine
<0.99
0.99 to 1.63
—
>1.63
cysteinylglycine
<1.01
1.01 to 1.43
—
>1.43
5,6-dihydrouridine
<1.01
1.01 to 1.84
—
>1.84
pseudouridine
<1.01
1.01 to 1.83
—
>1.83
5-methylthioribose
<1.01
1.01 to 1.53
—
>1.53
3,4-methylenevaleroylglycine
<1.02
1.02 to 1.42
—
>1.42
cysteine-glutathione disulfide
<1.02
1.02 to 1.52
—
>1.52
N-methylpipecolate
<1.03
1.03 to 1.43
—
>1.43
7-methylurate
<1.03
1.03 to 1.32
—
>1.32
ribonate
<1.03
1.03 to 1.55
—
>1.55
N1-Methyl-2-pyridone-5-
<1.04
1.04 to 1.66
—
>1.66
carboxamide
1-methyl-4-imidazoleacetate
<1.05
1.05 to 1.56
—
>1.56
S-methylcysteine
<1.06
1.06 to 1.38
—
>1.38
creatinine
<1.07
1.07 to 2.03
—
>2.03
N-acetylserine
<1.1
1.1 to 1.54
—
>1.54
pyridoxate
<1.11
1.11 to 1.38
—
>1.38
gulonate
<1.11
1.11 to 1.47
—
>1.47
N-carbamoylputrescine
<1.14
1.14 to 1.65
—
>1.65
norvaline
<1.17
1.17 to 1.42
—
>1.42
tryptophan
>1.05
1.05 to 0.73
—
<0.73
phenyllactate (PLA)
>1.08
1.08 to 0.71
—
<0.71
dihydroorotate
>1.1
1.1 to 0.67
—
<0.67
N-acetylglycine
>1.11
1.11 to 0.64
—
<0.64
beta-guanidinopropanoate
>1.11
1.11 to 0.64
—
<0.64
5-oxoproline
>1.12
1.12 to 0.62
—
<0.62
5-hydroxylysine
>1.13
1.13 to 0.61
—
<0.61
cholate
>1.14
1.14 to 0.62
—
<0.62
azelate (C9-DC)
>1.16
1.16 to 0.61
—
<0.61
N-acetylvaline
>1.22
1.22 to 0.77
—
<0.77
glycylvaline
>1.23
1.23 to 0.77
—
<0.77
heptanoylglutamine
>1.23
1.23 to 0.76
—
<0.76
isovalerate (i5:0)
>1.26
1.26 to 0.75
—
<0.75
butyrylputrescine/isobutyrylputrescine
>1.28
1.28 to 0.77
—
<0.77
homoarginine
>1.28
1.28 to 0.77
—
<0.77
homostachydrine
>1.28
1.28 to 0.75
—
<0.75
N6-methyladenosine
>1.28
1.28 to 0.75
—
<0.75
3-methoxytyramine
>1.29
1.29 to 0.91
—
<0.91
N-acetylhistamine
>1.29
1.29 to 0.79
—
<0.79
ferulylglycine (1)
>1.29
1.29 to 0.78
—
<0.78
S-methylcysteine sulfoxide
>1.3
1.3 to 0.84
—
<0.84
cyclo(pro-tyr)
>1.3
1.3 to 0.75
—
<0.75
N-lactoyl leucine
>1.31
1.31 to 0.74
—
<0.74
histamine
>1.31
1.31 to 0.72
—
<0.72
gamma-glutamylglycine
>1.31
1.31 to 0.73
—
<0.73
putrescine
>1.32
1.32 to 0.78
—
<0.78
alanyllysine
>1.32
1.32 to 0.74
—
<0.74
chenodeoxycholic acid sulfate (2)
>1.32
1.32 to 0.74
—
<0.74
N2,N2-dimethylguanosine
>1.33
1.33 to 0.77
—
<0.77
S-adenosylmethioninamine
>1.33
1.33 to 0.76
—
<0.76
betaine
>1.33
1.33 to 0.75
—
<0.75
dihydrobiopterin
>1.33
1.33 to 0.73
—
<0.73
methylmalonate (MMA)
>1.34
1.34 to 0.89
—
<0.89
2-methylbutyrylglycine
>1.34
1.34 to 0.75
—
<0.75
glycerophosphoglycerol
>1.35
1.35 to 0.79
—
<0.79
cadaverine
>1.36
1.36 to 0.77
—
<0.77
glucuronide of C10H18O2 (11)
>1.41
1.41 to 0.77
—
<0.77
and
(ii) determining that the feline has CKD if the normalized relative abundance of the first urine biomarker has a value outside the range under the non-CKD column, determining that the feline has early-stage chronic kidney disease if the normalized relative abundance of the first urine biomarker has a value in the range under the early-stage CKD column, or determining that the feline has late-stage CKD if the normalized relative abundance of the first urine biomarker has a value in the range under the late-stage CKD column;
and
(b) recommending a composition for the feline, wherein the composition treats or slows the progression of CKD in the feline, wherein the composition includes a combination of glycine, methionine, cysteine and glutamine.

921 more elements

Facts

Application

18/085,795Filed 21 Dec 2022 · us provisional application

Priority

27 Dec 2021

Published

US 2023/0204604 A129 Jun 2023

Granted

24 Mar 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

G01N 33/50
Biological material, e.g. blood, urine ; Haemocytometers: chemical analysis of biological material, e.g. blood, urine; Testing involving…
G01N 33/6893
Involving proteins, peptides or amino acids: related to diseases not provided for elsewhere
G01N 2570/00
Omics
G01N 2800/347
Genitourinary disorders: renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis;…