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Use of shroom3 in chronic kidney disease and chronic allograft nephropathy

a technology of allograft nephropathy and kidney disease, which is applied in the direction of drugs, instruments, immunological disorders, etc., can solve the problems of increasing the risk of cardiovascular disease and all-cause mortality, and no effective anti-fibrotic therapy to prevent the progression of ckd, so as to reduce renal function and increase the expression of shroom3

Inactive Publication Date: 2022-02-24
MT SINAI SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a new gene called SHROOM3 that is associated with kidney disease and transplant rejection. The gene is found to be up-regulated in kidneys that have been rejected or are failing. The patent provides a method for identifying patients at risk for developing kidney disease by measuring SHROOM3 expression in a kidney biopsy specimen. The method can help predict which patients will develop chronic allograft nephropathy (CAN) or chronic kidney disease (CKD) and can help guide treatment decisions. The patent also provides a kit for identifying patients at risk for CAN or CKD.

Problems solved by technology

In addition to conferring risk for end stage renal disease (ESRD), CKD increases the risk of cardiovascular disease and all-cause mortality {Weiner D, 2004}.
To date, there is no effective anti-fibrotic therapy to prevent the progression of CKD or CAN.

Method used

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  • Use of shroom3 in chronic kidney disease and chronic allograft nephropathy
  • Use of shroom3 in chronic kidney disease and chronic allograft nephropathy
  • Use of shroom3 in chronic kidney disease and chronic allograft nephropathy

Examples

Experimental program
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example 1

[0060]SHROOM3 is Upregulated and Associated with Progression of CAN

[0061]To identify genes that could potentially contribute to the development of CAN we performed an interim analysis for the first 66 subjects of the cohort who had the gene expression microarray data from the 3-month allograft biopsy as well as eGFR_12 and CADI_12. A list of candidate genes involved in CAN progression—that is, genes whose expression in the 3-month allograft sample correlated with a low eGFR_12 as well as a high CADI_12—were identified and ranked. SHROOM3 was among the top-ranked genes on the list (Table 3). Since the interim analysis, we have collected and analyzed additional samples. At the time of preparation of the instant application, 3-month allograft gene expression profiles have been performed on 160 allografts and of which 12-month eGFR (eGFR 12) was available in 147 subjects and 12-month CADI (CADI_12) was available in 101 subjects (FIG. 1). When we reexamined the correlation of 3-month all...

example 2

[0062]Association of SHROOM3 and CAN Progression Exists in Caucasian-Donor Allografts

[0063]Since a genetic variant of SHROOM3 (SNP variant rs17319721) is associated with CKD when studied in predominantly Caucasian cohorts [Kottgen A, 2009], we sought to determine whether the relationship observed between SHROOM3 and CAN followed a racial predilection. Of the 147 allografts with available eGFR_12, 109 were from Caucasian donors and their SHROOM3 expression was inversely correlated with eGFR_12 (r=−0.2712, P=5; n=7) (P=0.03, FIG. 3C).

example 3

[0064]A Non-Coding SHROOM3 Variant in the Donor is Associated with Increased SHROOM3 Expression

[0065]The A-allele (minor allele) of a non-coding SHROOM3 SNP at rs17319721 has been strongly linked to chronic kidney disease by eGFR-creatinine [Kottgen A, 2009; Boger C, 2011]. We performed targeted SNP genotyping for the rs17319721 variant in 540 allograft recipients and 468 donor samples. Allelic prevalence of the risk allele (A) was 36.66% among recipients and 40.02% among donors. In both recipients and donors, we observed that the prevalence of the risk allele was significantly higher in Caucasians compared to non-Caucasians (P<0.0001) (FIG. 6A). Since a higher SHROOM3 expression correlates with CAN progression and the risk allele of SHROOM3 is associated with CKD in predominantly Caucasian cohorts, here we examined whether allograft SHROOM3 expression correlated with the presence of the risk allele. Of the 160 allografts for which SHROOM3 expression was available, targeted SNP geno...

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Abstract

A method for identifying the risk of developing Chronic Allograft Nephropathy (CAN) in a patient that received a kidney transplant from a donor which comprises identifying the race of the donor; determining the levels of SHROOM 3 expression in a kidney biopsy specimen obtained from the patient at a predetermined time after transplant; comparing the level of SHROOM 3 expression in the biopsy specimen with the levels of SHROOM 3 expression in a control; determining if the level of SHROOM 3 expression in the allograft is significantly higher than in the control, and diagnosing the patient as being at risk for CAN if the level of SHROOM 3 expression in the specimen is significantly higher than in the control.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional, and claims priority to U.S. application Ser. No. 14 / 773,687, filed Sep. 8, 2015, now U.S. Pat. No. 11,098,361, issued Aug. 24, 2021, which is the U.S. National Phase Application under 35 U.S.C. § 371 of International Patent Application No. PCT / US2014 / 022607 filed Mar. 10, 2014, which claims the benefit of U.S. Provisional Application No. 61 / 777,328 filed Mar. 21, 2013, all of which are incorporated by reference herein. The International Application was published in English on Oct. 2, 2014 as WO2014 / 159227 A1 under PCT Article 21(3).GOVERNMENT CLAUSE[0002]This invention was made with government support under 1U01AI070107-01 awarded by The National Institutes of Health. The government has certain rights in the invention.SEQUENCE LISTING[0003]This application contains a Sequence Listing that has been submitted electronically as an ASCII text file named 27527-0124002SEQ.txt. The ASCII text file, created on Se...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/6883
CPCC12Q1/6883C12Q2600/156C12Q2600/158G01N2500/10C12Q2600/136G01N2800/50G01N2800/347C12Q2600/118G01N2800/245G01N33/6893A61K38/05A61K38/13A61P13/02A61P13/12A61P37/06A61P43/00
Inventor MURPHY, BARBARAHE, JOHN CIJIANG
Owner MT SINAI SCHOOL OF MEDICINE
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