CN101995428A - Method for early diagnosing acute kidney injury caused by contrast medium by utilizing MBL (mannan-binding lectin) - Google Patents
Method for early diagnosing acute kidney injury caused by contrast medium by utilizing MBL (mannan-binding lectin) Download PDFInfo
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- CN101995428A CN101995428A CN2009101944777A CN200910194477A CN101995428A CN 101995428 A CN101995428 A CN 101995428A CN 2009101944777 A CN2009101944777 A CN 2009101944777A CN 200910194477 A CN200910194477 A CN 200910194477A CN 101995428 A CN101995428 A CN 101995428A
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Abstract
The invention relates to a method for early diagnosing an acute kidney injury caused by a contrast medium by utilizing urine MBL (mannan-binding lectin), which comprises the following steps of: comparing fluorescence difference electrophoresis charts of the urine of a patient 24 hours after an operation and the basis urine of the patient before the operation, and searching out a plurality of differentially expressed protein spots; identifying through a matrix-supported laser desorption ionization time of flight mass spectrometry technique to discover that the mannan-binding lectin (MBL) and serine protease related to the MBL are both increased in the differentially expressed protein spots, and the difference has a statistical significance for prompting that the acute kidney injury caused by the contrast medium is related to a pathway of MBL (mannan-binding lectin) complement activation, which is verified by a patient with the kidney injury caused by the contrast medium through an urine ELISA (enzyme-linked immuno sorbent assay) way. If applied to the clinic, the method of the invention can be used for detecting the urine MBL (mannan-binding lectin) 24 hours after an operation through the ELISA (enzyme-linked immuno sorbent assay) way and early diagnosing the kidney injury caused by the contrast medium, which is 24 hours earlier than the diagnosis of serum creatinine, and provides basis for early clinical diagnosis, early treatment and improvement of prognosis.
Description
Technical field
The present invention relates to medical domain, relate in particular to a kind of clinical medicine check of can directly applying to, (mannose binding lectin, Mannose binding lectin MBL) are used for the method for the acute injury of kidney due to the early diagnosis contrast preparation to utilization MBL.
Background technology
Along with shadowgraph technique in clinical widespread use, particularly at advanced age, the application among the serious complication patient is arranged, (contrast induced nephropathy CIN) becomes the third-largest main cause of hospital acquired renal failure to radiographic contrast nephropathy, accounts for 11% of the incidence of disease.In the U.S., the annual radiography operation that has 1,000,000 times approximately, the incidence of CIN reaches 150,000 times/year; It is that example illustrates that patient with at least 1% needs dialysis treatment, and the patient's hospital stays that does not need to dialyse on average prolongs 2 days, need every day to suppose cost, annual therefore and the medical expense that increases up to, 000,000.And in case that the renal failure consequence takes place is very serious, be 36%, 2 year survival rate only 19% in institute's mortality ratio.Yet, the diagnosis of acute injury of kidney (AKI), tradition depends on the rapid rising of serum creatinine level or the change of urine amount.But, because part A KI and without the variation of urine amount; SCr raises and also lags behind the decline of actual glomerular filtration rate(GFR (GFR).Therefore, tradition depends on the method for acute injury of kidney due to the change early diagnosis contrast preparation of the rapid rising of serum creatinine level or urine amount, not only there is certain misdiagnosis rate, and the most important thing is to make a definite diagnosis time lag, be unfavorable for early diagnosis, early intervention in actual disease time.
Summary of the invention
The object of the present invention is to provide a kind of MBL of utilization to realize the method for acute injury of kidney due to the early diagnosis contrast preparation, to solve the technical matters of making a definite diagnosis time lag and poor specificity in the prior art.
In order to achieve the above object, the present invention proposes the method that a kind of MBL of utilization realizes acute injury of kidney due to the early diagnosis contrast preparation.Promptly, utilization fluorescence difference electrophoresis and matrix support laser to resolve the differential expression of the early stage urine protein spectrum of ion flight time mass spectrum technical research contrast preparation injury of kidney, search special urine diagnosis marker, and the detection by the early stage urine of contrast preparation injury of kidney patient and blood, determine mannose binding lectin (Mannose binding lectin, clinical use value MBL).
That is to say, the method of acute injury of kidney due to the utilization urine MBL realization early diagnosis contrast preparation of the present invention, comprise: the comparison of the fluorescence difference electrophoretogram of basic urine before 24 hours patients' of postoperative urine and the art searches out the protein site of several differential expressions; Support laser to resolve the technical appraisement of ion flight time mass spectrum through matrix again, find in those discrepancys, the serine protease that mannose binding lectin MBL is relevant with MBL all increases, and difference has statistical significance, the prompting contrast preparation due to acute injury of kidney relevant with MBL complement activation approach.And in contrast preparation injury of kidney patient, obtains to verify by urine ELISA method.If apply to clinically, can postoperative twenty-four-hour urine liquid MBL be detected by the method for ELISA, can be used for the early diagnosis of radiographic contrast nephropathy, can be than serum creatinine diagnosis in 24 hours ahead of time, for clinical diagnosis morning, early treatment, improve prognosis foundation is provided.
Embodiment
Now, more and more viewpoints think that SCr is not a sensitivity, special, reliable diagnostic index to AKI.The research of new diagnostic markers can and instruct treatment that foundation is provided for early diagnosis, early intervention.Other body fluid samples such as urine and serum are compared, and that its albumen constitutes is simple relatively, good stability, be easy to analyze, and can be used for the detection of human multiple disease, and particularly disease in the urological system is than the better clinical samples of serum.
The applicant discovers at present, the apolipoprotein (NGAL) that urine interleukin 18 (IL-18), urine neutrophil leucocyte gelatinase are correlated with etc. may can be used as the early diagnosis sign of AKI, but the diagnostic value in the acute injury of kidney due to the acute kidney popular name for, particularly contrast preparation is not seen relevant report as yet about the urine mannose binding lectin.
For this reason, the applicant has proposed the method that a kind of MBL of utilization realizes acute injury of kidney due to the early diagnosis contrast preparation.Promptly, utilization fluorescence difference electrophoresis and matrix support laser to resolve the differential expression of the early stage urine protein spectrum of ion flight time mass spectrum technical research contrast preparation injury of kidney, search special urine diagnosis marker, and the detection by the early stage urine of contrast preparation injury of kidney patient and blood, determine mannose binding lectin (Mannose binding lectin, clinical use value MBL).
Find basic urine before 24 hours patients' of postoperative urine and the art in the research about contrast preparation injury of kidney urine early diagnosis marker in early stage.
Need to prove, urine is directly discharged from kidney, the acute kidney popular name for there is very important diagnostic significance, the serodiagnosis index lags behind the generation of acute kidney popular name for, and poor specificity, so international research trend is the exploitation of urine diagnosis index at present, this application is just at urine MBL diagnosis CIN, and follow-up experiment is found, the horizontal preoperative and postoperative of blood MBL does not obviously change, the comparison of fluorescence difference electrophoretogram searches out the protein site (such as adopting 56 differential expression points) of several differential expressions.Identify through MALDI-TOF-mass spectrum (matrix supports laser to resolve ion flight time mass spectrum technology) again, find the serine protease that wherein MBL is relevant with MBL (MBL associated serine protease 2) all obviously increase (such as, the amplitude that increases is higher than a certain thresholding), because these 2 kinds of proteinase are all relevant with complement activation and cellular damage pathogenesis, the prompting radiographic contrast nephropathy may be relevant with MBL complement activation approach, and the detection of urine MBL may can be used as the important evidence of early diagnosis.Serine protease is the index that clinical detection needs good stability, and the relative serine protease relevant with MBL of MBL is more stable, is not easy to be subjected to the influence of factors such as temperature, time, is convenient to the enforcement that clinical ELISA detects.
MBL is comparatively stable in urine, is not easy to be subjected to the influence of storage temperature and time, so postoperative twenty-four-hour urine liquid MBL can be used for the early diagnosis of CIN, can be than SCr diagnosis in 24 hours ahead of time, and for clinical diagnosis morning, early treatment, improve prognosis foundation is provided.
In order to verify this research of applicant, the applicant has done an experiment for this reason.
The urine of selecting 13 routine CIN patients and 18 example pairing patients else detects, and with the value of checking MBL to the radiographic contrast nephropathy early diagnosis, finds that the more non-CIN group of CIN group postoperative twenty-four-hour urine liquid obviously raises, [2.080 (1.420,5.720) vs 1.411 (0.738,1.855) ng/L, P=0.002].Postoperative MBL and CIN morbidity ROC tracing analysis show that area under curve reaches 77.8%.Tracing analysis shows that area under curve reaches 82.9% to the absolute value that the MBL postoperative rises to CIN morbidity row ROC, and when postoperative rising absolute value was 1.1ng/L, the susceptibility of diagnosis and specificity were respectively 69.2% and 88.9%.And 24 hours after surgery, conventional sign thing SCr yet there are no obvious rising, and SCr needs ability diagnosis in postoperative 48-72 hour.And 24 hours serum MBL of postoperative value does not have significant difference [1.08 (0.755,1.629) vs 0.835 (0.417,1.313) mg/L, P=0.943] between CIN group and non-CIN group.
So postoperative twenty-four-hour urine liquid MBL can be used for the early diagnosis of CIN, can be than SCr diagnosis in 24 hours ahead of time, for clinical diagnosis morning, early treatment, improve prognosis foundation is provided.
That is, basic value compares before utilization urine MBL postoperative and the art, the 1.1ng/L if 24 hours absolute values of postoperative have risen before than art then can be used to diagnose the generation of CIN, and specificity and susceptibility all can reach 69.2% and 88.9%.Can be used for the early diagnosis of CIN, help and early treatment and improve prognosis.Make the more urgent patient can be after accepting radiography, the generation of early diagnosis acute injury of kidney, thus in time take measures, prevent that ephrosis from entering the dialysis stage, can reduce national medical expenses.Reach good social benefit and economic benefit.
More than disclosed only be several specific embodiment of the present invention, but the present invention is not limited thereto, any those skilled in the art can think variation, all should drop in protection scope of the present invention.
Claims (4)
1. a method of using MBL to realize acute injury of kidney due to the early diagnosis contrast preparation is characterized in that, comprising:
The comparison of the fluorescence difference electrophoretogram of basic urine before postoperative some hrs patient's urine and the art searches out the protein site of several differential expressions;
Support laser to resolve the technical appraisement of ion flight time mass spectrum through matrix again, find on average increasing of mannose binding lectin MBL is relevant with MBL in those discrepancys serine protease in a certain thresholding, but acute injury of kidney due to the tentative diagnosis contrast preparation then.
2. the method for claim 1 is characterized in that, the protein site of differential expression is 56.
3. the method for claim 1 is characterized in that, the postoperative some hrs is postoperative 24 hours.
4. the method for claim 1, it is characterized in that, detect through the ELISA method, on average the increasing of the serine protease that the mannose binding lectin MBL in those discrepancys is relevant with MBL, but as if the then generation of tentative diagnosis CIN of 1.1ng/L of having risen before than art of 24 hours absolute values of postoperative.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104133027A (en) * | 2014-06-24 | 2014-11-05 | 江南大学 | Method for separating and identifying glycoprotein N-sugar chain structure |
| CN108139409A (en) * | 2015-10-08 | 2018-06-08 | 豪夫迈·罗氏有限公司 | When being measured before surgical operation for predicting the IGFBP7 of the risk of AKI |
-
2009
- 2009-08-24 CN CN2009101944777A patent/CN101995428A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104133027A (en) * | 2014-06-24 | 2014-11-05 | 江南大学 | Method for separating and identifying glycoprotein N-sugar chain structure |
| CN108139409A (en) * | 2015-10-08 | 2018-06-08 | 豪夫迈·罗氏有限公司 | When being measured before surgical operation for predicting the IGFBP7 of the risk of AKI |
| US11397187B2 (en) | 2015-10-08 | 2022-07-26 | Roche Diagnostics Operations, Inc. | IGFBP7 for prediction of risk of AKI when measured prior to surgery |
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Application publication date: 20110330 |