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CN-121978343-A - Application of urine TRPV5 as biomarker in chronic kidney disease diagnosis and risk assessment

CN121978343ACN 121978343 ACN121978343 ACN 121978343ACN-121978343-A

Abstract

The invention provides application of urine TRPV5 as a biomarker in diagnosis and risk assessment of chronic kidney disease, and discovers that TRPV5 and a detectable fragment thereof exist in urine for the first time, the content of the TRPV5 in the urine is positively correlated with Chronic Kidney Disease (CKD), the diagnosis of the CKD can be carried out by detecting the content of the TRPV5 in the urine, and a specific in-vitro diagnosis method and a specific kit thereof are provided. The in-vitro diagnosis method overcomes the defects of the existing CKD diagnosis technology, provides a brand-new diagnosis tool which is noninvasive, sensitive and specific and can be used for stage and prognosis evaluation, and has obvious technological progress and wide clinical application prospect.

Inventors

  • GUO XINRU
  • WANG XINGYU
  • WANG WENJUAN
  • CHANG QING
  • Li Mianyang
  • CHEN XIANGMEI
  • CAI GUANGYAN

Assignees

  • 中国人民解放军总医院第一医学中心

Dates

Publication Date
20260505
Application Date
20251230

Claims (10)

  1. Use of trpv5 protein or a characteristic fragment thereof in the preparation of a product for in vitro diagnosis or screening of chronic kidney disease.
  2. Use of trpv5 protein or a fragment characteristic thereof for the preparation of a chronic kidney disease risk prediction product.
  3. Use of trpv5 protein or a fragment characteristic thereof for the preparation of a product for prognosis monitoring of chronic kidney disease.
  4. 4. The use according to any one of claims 1-3, characterized in that said use is a significant increase in TRPV5 protein expression, or a significant increase in the content of a characteristic fragment or a hydrolytic fragment thereof, which is indicative of a patient to be tested being at a high risk or poor prognosis of chronic kidney disease.
  5. 5. The use according to any one of claims 1-3, wherein the product is a detection reagent, a detection kit, wherein the reagent is used for detecting the expression level of TRPV5 protein or the characteristic fragment content thereof; The reagent is used for ELISA, protein/peptide fragment chip detection, immunoblotting, microbead immunodetection or microfluidic immunodetection, and is preferably used for detecting the content of the TRPV5 protein or the characteristic fragment or the hydrolysis fragment thereof through antigen-antibody reaction.
  6. 6. The use according to claim 4, wherein the test object of the test reagent or test kit is urine, preferably urine supernatant.
  7. 7. The use according to claim 5, wherein the judgment principle is that a predetermined threshold is determined based on healthy people, and when the TRPV5 protein or the characteristic fragment thereof or the hydrolyzed fragment thereof in the sample to be tested is significantly higher than the predetermined threshold, the patient to be tested is at a high risk of chronic kidney disease or chronic kidney disease.
  8. 8. A kit for in vitro diagnosis or screening of chronic kidney disease, characterized in that it contains a test reagent for the characteristic fragment content of TRPV5 protein, and the test object of the kit is urine supernatant.
  9. 9. The kit of claim 7, wherein the kit detection threshold is 297.6 pg/mL, above which is indicative of a patient subject to be tested for urine suffering from or at risk of suffering from chronic kidney disease.
  10. 10. The kit of claim 7, wherein when the kit detects CKD stage 1 and/or CKD stage 2, the detection threshold is 309.0 pg/mL above which the patient's body to be tested for urine is in CKD stage 1 and/or CKD stage 2.

Description

Application of urine TRPV5 as biomarker in chronic kidney disease diagnosis and risk assessment Technical Field The invention relates to the technical field of clinical diagnosis, in particular to application of urine TRPV5 as a biomarker in diagnosis and risk assessment of chronic kidney disease. Background Chronic kidney disease (Chronic KIDNEY DISEASE, CKD) is a global public health problem, known by its high incidence, low awareness and risk of developing end stage renal disease. Its early diagnosis is critical for slowing disease progression and improving patient prognosis. Currently, clinical diagnosis and staging of CKD is mainly dependent on serum creatinine (SCr) and estimated glomerular filtration rate (gfr), urinary albumin/creatinine ratio (ACR), renal biopsy, etc. However, serum creatinine levels are affected by age, sex, race, muscle mass, and other non-renal factors, and are not sufficiently sensitive. The eGFR is estimated by a formula, is not sensitive enough in the early stage of the mild decline of renal function (CKD 1-2 stage), often has obvious change when the loss of renal function exceeds 50%, and cannot realize early warning. Urinary albumin/creatinine ratio (ACR) is a key indicator for diagnosing glomerular injury (e.g., diabetic nephropathy). It reflects mainly the damage to the glomerular filtration barrier and is less sensitive to the type of CKD that is first or predominantly manifested by tubular interstitial lesions. Renal biopsy is a gold standard for pathological diagnosis, and can determine the type and extent of injury. However, it is an invasive procedure, has the risk of bleeding, infection, etc., and cannot be used for routine screening, dynamic monitoring, and population screening. In view of the above, the prior art has the defects of insensitivity, invasiveness or susceptibility to interference and the like to the early-stage specific injury of the tubular, and there is a great clinical need for noninvasive biomarkers capable of specifically and sensitively reflecting the health state of the tubular. Transient receptor potential vanilloid subtype 5 (TRANSIENT RECEPTOR POTENTIAL VANILLOID, TRPV 5) is a highly calcium selective epithelial calcium ion channel that is predominantly distributed in the distal tubular and connective tubular top membranes of the kidney, responsible for calcium ion reabsorption, a "gatepost" of kidney calcium metabolism. TRPV5 plays a central role in maintaining calcium balance in vivo. Currently, there are some documents that disclose the correlation of TRPV5 with kidney diseases at the tissue level. For example, on academic journal Journal of Clinical Investigation (2003, 112 (12), 1906-1914), joost G J Hoenderop et al, paper "Renal Ca2+ wasting, hyperabsorption, and reduced bone THICKNESS IN MICE LACKING TRPV" states that TRPV5 knock-out mice exhibit significant loss of renal calcium and reduced bone density. Another article "Downregulation of Ca(2+) and Mg(2+) transport proteins in the kidney explains tacrolimus (FK506)-induced hypercalciuria and hypomagnesemia" published in Journal of THE AMERICAN Society of Nephrology (2004; 15 (3): 549-57.) found that the immunosuppressant tacrolimus down regulates the expression of TRPV5 in the renal tubules and initiates hypercalcemia. The mechanism of action of the prior art is in agreement with the blank that these studies indicate that TRPV5 protein expression in kidney tissue is altered in the disease state. However, all these studies are limited to analysis of kidney tissue itself, and their technical means (e.g., gene knockout, tissue Western Blot, immunohistochemistry) are invasive and cannot be converted into clinical diagnostic tools. To date, no prior art discloses or suggests: TRPV5 protein or hydrolytic fragment thereof is present in human urine supernatant. TRPV5 protein concentration in urine has a correlation with CKD diagnosis and proteinuria severity. These proteins in urine can be detected noninvasively by commercial immunological detection methods (e.g., ELISA) and developed as a completely new clinical diagnostic marker. Disclosure of Invention Aiming at the defects existing in the prior art, the invention provides application of urine TRPV5 serving as a biomarker in diagnosis and risk assessment of chronic kidney disease, which is used for solving the defect that the prior art lacks an early-onset in-vitro diagnosis means of CKD and providing a brand-new and noninvasive in-vitro diagnosis and risk assessment solution of CKD. In a first aspect, the present invention provides the use of TRPV5 protein or a characteristic fragment thereof in the preparation of an in vitro diagnostic or screening product for chronic kidney disease. In particular to the application of a reagent for detecting TRPV5 protein or a characteristic fragment thereof in preparing a product for in vitro auxiliary diagnosis of chronic kidney disease of a subject. In the prior art, TRPV5 research has focused on i