MMP9:TIMP2 Biomarker Assay for Early Acute Kidney Injury Detection

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Solution Overview

Problem

Current methods for detecting acute kidney injury (AKI) rely heavily on serum creatinine measurements, which are limited in early detection, differentiation of causes, and monitoring of kidney function, particularly in acute phases, leading to delayed diagnosis and inadequate management.

Innovation Solution

The use of a method involving assays to detect the matrix metalloproteinase-9:tissue inhibitor of metalloproteinase 2 (MMP9:TIMP2) complex and other biomarkers in urine samples to evaluate the likelihood of RIFLE stage I or F acute kidney injury within 48 hours, providing earlier and more accurate assessment of renal function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If serum creatinine measurements are used to detect acute kidney injury, then the method is simple and widely available, but the detection is delayed and lacks precision in early phases

Engineering Contradiction:
Improveearly detection accuracyVSAvoiddiagnosis delay
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent measures MMP-9:TIMP-2 complex concentrations before acute kidney injury fully develops or in the very early phases, enabling prediction and early intervention before traditional creatinine markers show abnormalities. This preliminary detection approach allows clinicians to take preventive actions before the injury progresses to detectable stages by conventional methods.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces MMP-9:TIMP-2 complex as an intermediary biomarker that provides earlier and more sensitive information about renal injury than creatinine. This intermediary marker bridges the gap between actual injury occurrence and detectable functional changes, allowing detection before the kidney function deteriorates to levels measurable by traditional methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If serum creatinine is used to monitor kidney function, then the assay is simple and inexpensive, but it cannot differentiate between various causes of renal injury

Engineering Contradiction:
Improvecause differentiation capabilityVSAvoidassay complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent segments the monitoring approach by measuring multiple distinct biomarkers (MMP-9:TIMP-2 complex and other urinary markers) rather than relying on a single creatinine measurement. Each biomarker provides specific information about different aspects of renal injury, allowing differentiation between various causes and stages of kidney damage while maintaining relatively simple individual assays.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs a multi-functional biomarker panel where MMP-9:TIMP-2 complex and accompanying urinary markers serve multiple purposes: detecting injury presence, differentiating injury causes, staging injury severity, and monitoring progression. This universal approach replaces the single-function creatinine test with a comprehensive marker system that addresses multiple diagnostic needs simultaneously.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If traditional renal function markers are used, then the monitoring is straightforward, but the management is inadequate due to delayed and imprecise detection

Engineering Contradiction:
Improvediagnosis reliabilityVSAvoidmonitoring simplicity
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent performs preliminary risk assessment by measuring MMP-9:TIMP-2 complex concentrations before acute kidney injury develops or in very early phases. This allows identification of at-risk patients who can receive preventive interventions, improving diagnostic reliability by detecting injury before it progresses to irreversible damage while maintaining operational simplicity through a single primary biomarker measurement.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP3339860B1Methods and compositions for diagnosis and prognosis of renal injury and renal failure
Publication Date: 2025.01.01 ASTUTE MEDICAL INC
  • EP3339860B1 patent drawing
  • EP3339860B1 patent drawing
  • EP3339860B1 patent drawing

AI summary

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect MMP9:TIMP2 complex and optionally further a kidney injury marker of Thymic stromal lymphopoietin, Vascular endothelial growth factor receptor 1, C-C motif chemokine 1, C-C motif chemokine 17, C-C motif chemokine 21, C-C motif chemokine 27, FLT-3 Ligand, Immunoglobulin G subclass 3, Interleukin-1 receptor type I, Interleukin-20, Interleukin-29, Interleukin-7, Platelet-derived growth factor A/B dimer, Platelet-derived growth factor A/A dimer, and as diagnostic and prognostic biomarkers in renal injuries.