Kynurenine Biomarker for Contrast-Induced Nephropathy Prediction

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Solution Overview

Problem

Current diagnostic methods cannot predict contrast-induced nephropathy (CIN) or distinguish it from major adverse renal events in patients with pre-existing renal impairment, lacking a reliable biomarker for identifying patients at risk before contrast media administration.

Innovation Solution

An in vitro diagnostic method measuring the concentration of kynurenine in body fluids, such as serum or urine, to determine the risk of CIN and the need for endothelial protective treatment, with a threshold value of 3.5 µmol/L for predicting increased risk of CIN, major adverse renal events, and cardiovascular events.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional biomarkers (creatinine, cystatin C, NGAL, KIM-1, homocysteine) are used for prediction, then some aspect of renal function monitoring is available, but they cannot reliably predict CIN or distinguish it from other renal events in patients with pre-existing renal impairment

Engineering Contradiction:
Improvepredictive reliability for CINVSAvoidbiomarker specificity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent changes the biomarker parameter from conventional markers (creatinine, cystatin C, NGAL) to kynurenine levels. This parameter change enables reliable pre-procedural prediction of CIN by measuring kynurenine concentrations in serum or plasma before contrast media administration, achieving both reliability and specificity that conventional markers cannot provide simultaneously

Inventive Principle:
Principle #35Parameter changes

2Loss of information

If no reliable biomarker is available, then patients at risk cannot be identified before CM administration, but using existing biomarkers leads to inability to distinguish CIN from other renal events

Engineering Contradiction:
Improverisk prediction informationVSAvoiddiagnostic accuracy
Core Design Contradiction:
Loss of informationVSReliability

Solution Approach 1:

The patent extracts the predictive information function from conventional biomarkers and isolates it into a specific measurement of kynurenine levels. This extraction allows the diagnostic system to specifically predict CIN risk without the confounding effects that plague other biomarkers, thereby recovering lost predictive information while maintaining high diagnostic accuracy

Inventive Principle:
Principle #2Taking out (Extraction)

3Loss of time

If monitoring of renal function by measuring serum creatinine is performed, then renal function can be tracked after CM administration, but it cannot predict CIN risk before the procedure

Engineering Contradiction:
Improveprediction timingVSAvoidrisk assessment accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent implements preliminary action by measuring kynurenine levels before contrast media administration rather than after. This pre-procedural measurement provides timely risk prediction that enables preventive measures to be taken before CIN occurs, eliminating the time loss associated with post-procedural monitoring while maintaining high measurement precision for risk assessment

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP3070475B1In vitro diagnostic, prognosis of contrast induced nephropathy
Publication Date: 2020.02.19 KELLNER KARL HEINZ
  • EP3070475B1 patent drawingFigure 1A~1B
  • EP3070475B1 patent drawingFigure 2
  • EP3070475B1 patent drawingFigure 3A~3B

AI summary

Method of in-vitro diagnosis of an increased risk for contrast-induced nephropathy (CIN) in a patient even before the patient is subjected to coronary angiography or any examination requiring the administration of a contrast medium. The disclosure comprises an immunological determination of the kynurenine concentration in serum and informs the physician of the risks of a MARE (major adverse renal event) or MACE (major cardiovascular event).