US 10,472,679 B2Granted

Non-invasive method of diagnosing renal fibrosis

AssigneeCornell University

InventorsManikkam Suthanthiran, Joseph E. Schwartz, Ruchuang Ding, Thangamani Muthukumar

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Abstract

Measurement of mRNAs in urinary cells offers a noninvasive means of diagnosing fibrosis in kidneys. One aspect of the invention is a method that includes: (a) measuring quantities of vimentin mRNA, NKCC2 mRNA, and E-cadherin mRNA in a test sample of cells obtained from urine; and (b) determining whether the vimentin mRNA quantity is higher, the NKCC2 mRNA quantity is lower, or the E-cadherin mRNA is higher than in healthy urinary cells; and thereby detecting that the sample is a fibrotic kidney sample. Step (a) can also include measuring the quantity of RNA expressed by a housekeeping gene (e.g., 18S rRNA). The quantities of vimentin mRNA, NKCC2 mRNA, and E-cadherin mRNA can be normalized against the quantity of housekeeping gene RNA.

Claims5

Dependent claims

A method comprising:

treating kidney fibrosis in a subject with a kidney transplant having renal fibrosis, wherein the method comprises:
quantitative nucleic acid amplification measurement of sample RNA from urinary cells of the subject using primers specific for vimentin, NKCC2, E-cadherin, and 18S rRNA;
calculating a composite score as follows:
Composite
⁢
⁢
Score
=
36.10283
+
[
-
15.84215
*
log
10
⁡
(
18
⁢
s
⁢
⁢
RNA
)
]
+
1.56907
*
log
10
⁡
(
18
⁢
s
⁢
⁢
RNA
)
*
log
10
⁡
(
18
⁢
s
⁢
⁢
RNA
)
+
5.11698
*
max
⁡
[
0
,
log
10
⁡
(
Vimentin
)
-
5.6
]
+
[
-
1.44145
*
log
10
⁡
(
NKCC
⁢
⁢
2
)
]
+
3.31357
*
min
⁡
[
3.1
,
log
10
⁡
(
E
⁢
-
⁢
cadherin
)
]
where,
log10(18s RNA) is log10 of 18S RNA quantity/105 in the test sample;
log10(Vimentin) is log10 of a normalized vimentin mRNA quantity in the test sample;
log10(NKCC2)] is log10 of a normalized NKCC2 mRNA quantity in the test sample;
log10(E-cadherin) is log10 of a normalized E-cadherin mRNA quantity in the test sample;
max[0, log10(Vimentin)−5.6]=0 whenever log10(Vimentin) is ≤5.6 and =log10(Vimentin−5.6 whenever log10(Vimentin) is >5.6;
min[3.1, log10(E-cadherin)]=log10(E-cadherin) whenever log10(Ecadherin)<3.1 and =3.1 whenever log10(E-cadherin)≥3.1;
and * signifies multiplication;
and
removal of the kidney transplant and transplantation of a second kidney transplant, or administering one or more anti-inflammatory agent, anti-coagulant, antioxidant, blood pressure medication, angiotensin-converting enzyme inhibitor, angiotensin AT1 receptor blocker, connective tissue growth factor inhibitor, or antifibrotic agent, when the composite score is 4.7 or more to thereby treat kidney fibrosis in a subject.

110 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/400,873Filed 15 May 2013 · us provisional application
Priority: 15 May 2012
Published: US 2015/0240305 A127 Aug 2015
Granted: 12 Nov 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C12Q 1/6883
Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes: for diseases caused by alterations of genetic material
G16H 50/20
ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or…: for…
C12Q 2600/118
Oligonucleotides characterized by their use: prognosis of disease development
C12Q 2600/156
Oligonucleotides characterized by their use: polymorphic or mutational markers