Urine mRNA Biomarker Detection for Acute Rejection
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Solution Overview
Problem
Current methods for diagnosing acute rejection in kidney transplants are invasive and lack sensitivity and specificity, leading to complications such as bleeding and graft loss, and do not allow for timely identification of rejection episodes, which can result in organ injury and dysfunction.
Innovation Solution
Measuring the levels of specific messenger RNAs (mRNAs) such as perforin, granzyme B, proteinase inhibitor-9, interferon-inducing protein-10, FoxP3, TGF-beta-1, CXCR3, and CD3 in urine samples to anticipate and diagnose acute cellular rejection using weighted combinations and logistic regression models, allowing for non-invasive prediction and diagnosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If core needle biopsy procedure is performed to diagnose acute rejection, then diagnostic accuracy is improved, but patient safety and ease of operation deteriorate due to complications such as bleeding, arteriovenous fistula, graft loss, and death
Solution Approach 1:
The patent replaces the mechanical invasive biopsy procedure with a molecular diagnostic system that measures mRNA levels in urine samples. This substitution eliminates the need for physical needle insertion into the graft while providing equivalent or superior diagnostic information through molecular biomarkers such as perforin, granzyme B, and IP-10 mRNA expression levels
Solution Approach 2:
The patent introduces urine as an intermediary medium to obtain diagnostic information about graft rejection. Instead of directly sampling the graft tissue through biopsy, the system uses urine samples that contain molecular markers reflecting graft status, thereby providing an indirect but safe diagnostic pathway
2Ease of operation
If serum creatinine level is measured to monitor kidney function, then ease of operation is improved, but measurement precision deteriorates because it lacks sensitivity and specificity to distinguish acute rejection from other causes of graft dysfunction
Solution Approach 1:
The patent segments the single non-specific serum creatinine measurement into multiple specific mRNA biomarker measurements. Instead of relying on one general function indicator, the system analyzes expression levels of multiple specific genes (perforin, granzyme B, IP-10, FoxP3, TGF-beta-1, CXCR3, CD3) that provide distinct immunologic information about rejection mechanisms
Solution Approach 2:
The patent changes the measurement parameter from serum creatinine (a general kidney function marker) to mRNA expression levels (specific molecular biomarkers). This parameter change transforms the diagnostic capability from detecting general graft dysfunction to specifically identifying immune-mediated rejection processes through weighted combinations and logistic regression models
3Ease of operation
If invasive biopsy procedure is avoided to improve patient safety, then ease of operation and patient safety are improved, but diagnostic capability and measurement precision deteriorate
Solution Approach 1:
The patent replaces the mechanical tissue sampling approach with a molecular detection system that analyzes mRNA in urine. This substitution maintains high diagnostic precision by measuring specific gene expression patterns associated with rejection while completely avoiding the mechanical trauma of needle biopsy
Solution Approach 2:
The patent changes from measuring physical tissue morphology through biopsy to measuring molecular expression parameters (mRNA levels) in urine. This parameter transformation enables non-invasive diagnosis while preserving diagnostic accuracy by detecting the molecular signatures of immune activation that characterize rejection
Data Source
AI summary
In some embodiments, a method to detect acute rejection in allograft from is described. In some embodiments, a method to anticipate an episode of acute rejection in allografts is also described. In some embodiments, a kit for detecting or predicting acute transplant rejection of a transplanted organ is described.