Urinary Protein Marker Panels for CKD and Glomerulopathy
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Solution Overview
Problem
Current diagnostic methods for chronic kidney disease (CKD) and glomerulopathies are invasive, unreliable, and lack effective tools for monitoring disease progression and response to treatment, particularly for conditions like IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN).
Innovation Solution
A method using a small set of protein markers, including serum albumin, ceruloplasmin, serotransferrin, alpha-1B-glycoprotein, and others, measured in urine samples to diagnose CKD and differentiate between various glomerulopathies, employing multiplexed peptide panels with targeted mass spectrometry-based methods for accurate quantitation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If kidney biopsy is used for diagnosis, then diagnostic reliability is improved, but patient safety and ease of operation deteriorate due to invasiveness and adverse effects
Solution Approach 1:
The patent uses urinary proteins as intermediary biomarkers that reflect kidney pathology without requiring direct tissue sampling. These proteins serve as mediators between the diseased kidney tissue and the diagnostic test, allowing indirect assessment of kidney status through urine analysis, thereby avoiding the harmful effects of invasive biopsy procedures
Solution Approach 2:
The patent replaces the mechanical invasive procedure of kidney biopsy with a non-invasive biochemical test analyzing urinary proteins. This substitution eliminates the need for physical tissue removal and analysis, replacing it with a molecular-level detection method that achieves diagnostic accuracy without mechanical trauma to the patient
2Reliability
If kidney biopsy is used for diagnosis, then diagnostic accuracy is improved, but patient safety deteriorates due to risk of death in severe cases
Solution Approach 1:
Urinary proteins serve as safe intermediary biomarkers that carry diagnostic information about kidney pathology without requiring direct access to kidney tissue. This intermediary approach provides the necessary diagnostic accuracy while completely eliminating the life-threatening risks associated with invasive biopsy procedures
Solution Approach 2:
The patent uses readily available urine samples instead of precious kidney tissue biopsies. Urine is a continuous, renewable fluid that can be collected repeatedly without harm, whereas kidney tissue is limited and its acquisition carries serious risks. This substitution provides multiple diagnostic opportunities without compromising patient safety
3Reliability
If kidney biopsy is used for diagnosis, then diagnostic capability is improved, but ease of operation deteriorates due to procedural complexity and inconclusive results
Solution Approach 1:
The patent replaces complex mechanical biopsy procedures with simple urine collection and protein analysis. This substitution dramatically simplifies the diagnostic workflow, eliminating the need for specialized surgical equipment, trained biopsy operators, and complex tissue processing laboratories, while providing conclusive diagnostic information
Solution Approach 2:
The diagnostic method enables patients to provide their own diagnostic sample (urine) without requiring invasive medical procedures. This self-service approach simplifies the diagnostic process, reduces healthcare resource utilization, and eliminates the complexity and risks associated with physician-performed biopsies
4Reliability
If traditional diagnostic methods are used, then diagnosis can be made, but ability to monitor disease progression and treatment response deteriorates
Solution Approach 1:
The patent enables continuous monitoring of kidney disease by analyzing urinary proteins at multiple time points. Unlike single-point biopsy diagnosis, this method allows repeated measurements to track disease progression and treatment response over time, providing continuous useful diagnostic information without repeated invasive procedures
Solution Approach 2:
The patent creates a feedback loop for disease monitoring by measuring urinary protein levels before and after treatment. These measurements provide feedback on treatment effectiveness, allowing clinicians to adjust therapy based on objective biomarker changes, thereby enhancing the adaptability and versatility of the diagnostic system
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables non-invasive, reliable differentiation between healthy individuals and CKD patients, as well as specific glomerulopathies, providing a means to monitor disease progression and treatment response.
Implementation Method 1
employing multiplexed peptide panels with targeted mass spectrometry-based methods for accurate quantitation
Data Source
AI summary
The object of the present invention is a method of diagnosis of a chronic kidney disease (CKD) or glomerulopathy in a subject, comprising the following steps: (a) determination of the level of at least three or four or five protein markers selected from the group consisting of serum albumin (ALB), alpha-1-antitrypsin (serpinal), alpha-1-acid glycoprotein 1 (ORM1), serotransferrin (TF) and trefoil factor 1 (TFF), wherein said markers also comprise the non-full-length fragments thereof, in a urine sample from said subject and (b) assigning a probability of the subject having or being at a risk of chronic kidney disease or glomerulopathy or not having nor being at a risk thereof based on the results of the assay of step (a), wherein this involves estimating a probability of the subject having or being at a risk of chronic kidney disease or glomerulopathy or not having nor being at a risk thereof based on the level of each of the marker levels determined in (a)), the probability being estimated based on the levels of each of the markers as determined in subjects known to suffer from a glomerulopathy or a chronic kidney disease; and determining the probability of the subject, providing the urine sample tested in step (a), having or being at a risk of a glomerulopathy or a chronic kidney disease or not having nor being at a risk thereof as a product of the corresponding probabilities obtained from each marker. A further object of the present invention is a method of monitoring a response to treatment of a chronic kidney disease (CKD) or glomerulopathy in a subject, comprising the following steps: a) measurement of the level, at a first point in time, for three or four or five of the markers selected from a group consisting of serum albumin (ALB), alpha-1-antitrypsin (serpinal), alpha-1-acid glycoprotein 1 (ORM1), serotransferrin (TF) and trefoil factor 1 (TFF), wherein said markers also comprise the non-full-length fragments thereof, in a urine sample from a subject; b) repeating the assay of step (a) at a later point in time after a period wherein the subject was undergoing a treatment; c) assessing a response to said treatment by comparing the results of the assays of steps (a) and (b), wherein lower marker levels after treatment are indicative of a positive response to treatment. A further object of the present invention is a method of treatment of a chronic kidney disease (CKD) or glomerulopathy in a subject, comprising the following steps: (a) determination of the level of at least three or four or five protein markers selected from the group consisting of serum albumin (ALB), alpha-1-antitrypsin (serpinal), alpha-1-acid glycoprotein 1 (ORM1), serotransferrin (TF) and trefoil factor 1 (TFF), wherein said markers also comprise the non-full-length fragments thereof, in a urine sample from said subject and (b) assigning a probability of the subject having or being at a risk of chronic kidney disease or glomerulopathy based on the results of the assay of step (a); (c) administering treatment against a chronic kidney disease (CKD) or glomerulopathy in the subject evaluated in step (b) as having or being at a risk of chronic kidney disease or glomerulopathy.