Early Diagnosis as Strategy in Reducing the Incidence of Contrast-induced Nephropathy
Condition: Kidney Injury; Contrast-induced Nephropathy
MeSH terms: Kidney Diseases
Study type: Observational

Summary: 
      Renal damage due to contrast media (CM) administration is one of the main complications of
      cardiac intervention and is called contrast-induced nephropathy (CIN). Patients suffering
      from CIN have a high probability of developing acute renal failure. Today there is no
      treatment capable of reversing kidney damage, so the best strategy is prevention, by early
      diagnosis. In this regard, a line of research is currently being carried out focused on the
      identification of new markers capable of detecting susceptibility/predisposition to renal
      damage before the administration of a potentially nephrotoxic drug, even at doses that alone
      should not produce Kidney damage. This concept has been called predisposition to kidney
      damage.

      Taking into account all of the above, the objective of this work is to evaluate the ability
      of the new markers (previously identified in preclinical models) to detect the predisposition
      to the CIN before administering the CM.
    

Detailed description: 
      Kidney damage is one of the most frequent complications of cardiac intervention. This
      pathology is called contrast-induced nephropathy (CIN) and is defined as an increase in
      plasma creatinine greater than or equal to 0.5 mg/dL, or greater than or equal to 25% with
      respect to baseline, during the 5 days after contrast medium (CM) administration.

      The appearance of acute renal damage significantly increases the health costs associated with
      interventional procedures. This is derived from the increase in the length of hospital stay,
      in care units, and from the application of dialysis as the only existing treatment. In the
      United States, it has been estimated that the development of acute in-hospital renal damage
      increases health expenditure by $ 7933 per patient per day, mainly due to the increase in
      hospitalization time. Thus, not only the very early detection, but especially the prevention
      of acute renal damage are key aspects for the prognosis of the patients, and for the control
      of the health expenditure associated with them.

      Iodized CMs are the leading cause of acute renal damage of toxic origin in humans. CMs
      produce renal ischemia derived from a vasoconstriction that has two effects: on the one hand
      reduction of glomerular filtration, and on the other, tubular ischemic damage that amplifies
      the reduction of filtrate and, with it, renal dysfunction.

      Different scales have been proposed to determine the risk of developing CIN, which include
      different variables such as the presence of arterial hypotension, the use of counterpulsation
      balloon, the age over 75 years, the presence of anaemia, diabetes, the amount of CM used and
      renal function. Each item is assigned a certain score in the case of being present in the
      patient and depending on the final score, the possible risk of contrast nephropathy after the
      procedure and even the risk of dialysis is estimated. However, these scales are not widely
      used in clinical practice and their usefulness is doubtful.

      Currently the detection of renal damage associated with CM is performed using the plasma
      creatinine marker. The main drawback of this detection mode is that creatinine levels
      increase when renal functionality is already altered. In other words, detection occurs when
      renal functionality has decreased by approximately 70%. This is why new markers capable of
      detecting damage in their earliest stages are currently being evaluated, when the damage is
      less widespread. Also in the last decade a new concept of biomarker called a marker of
      predisposition to kidney damage has emerged. This concept has been revealed after verifying
      that certain treatments significantly increase the risk of suffering an acute renal failure,
      and do so in a hidden and silent way.

      This susceptibility can be detected by certain markers, which if its usefulness is validated
      in clinical practice, this assessment would be a very useful tool to classify the risk of
      patients, individually. Thus the information provided by the predisposition markers would
      allow a preventive and personalized medicine to be carried out when subjecting patients to a
      new procedure or treatment potentially harmful to their kidneys.

      Taking into account all of the above, the objective of this work is to evaluate the ability
      of the new predisposition markers (previously identified in preclinical models) to detect
      patients at risk of suffering CIN before CM administration.

      To carry out this purpose, patients who are going to receive an CM will be recruited from the
      Cardiology Service of the University Assistance Complex of Salamanca (CAUSA). Patients who
      agree to be part of the study must sign an informed consent.

      DATA COLLECTION, SAMPLES AND PROCESSING Each patient is assigned an alphanumeric code,
      therefore their identity will only be known by the cardiology staff.

      At the time of inclusion in the study, the following information will be collected for each
      patient: date of sample collection, general data, anthropometric data, risk factors,
      prescribed drugs.

      Both before the CM administration and daily for the next 5 days, the plasma creatinine value
      obtained through the patient's medical history will be collected, since this is a
      determination that is made as part of the care procedure.

      A urine sample will be collected before the CM administration. This sample will be coded with
      the code mentioned above and will be taken to the CAUSA Sample Bank, where it will be
      centrifuged, aliquoted and stored at -80 degrees Celsius.

      URINE SAMPLES ANALYSIS The following determinations will be made: Proteinuria: marker used in
      the clinic, the Bradford colorimetric technique will be used; Early kidney damage markers and
      predisposition markers using colorimetric methods, ELISAs and Western Blot STATISTIC ANALYSIS
      A significance level of 0.05 will be used. The data analysis will be performed with STATA 10
      and Statistical Package for the Social Sciences (SPSS) 23.0. Different contrast will be
      applied depending on the association that is to be studied in each case, and the type of
      variables such as: normality test (Kolmogorov-Smirnov, Shapiro-Wilk), frequency comparison
      (X2), correlation test (Pearson, Spearman), comparison of means for independent data (ANOVA
      and Kruskal-Wallis) and repeated measures ANOVA and Wilcoxon test for paired data.

      STUDY LIMITATIONS Although the study follows all the recommendations for observational
      studies considered in the STORBE statement (STregthening the Reporting of OBservational
      studies in Epidemiology), there is a possibility that there are factors that have not been
      considered. On the other hand, the included variables are biomarkers of early kidney damage
      and predisposition to acute renal damage induced by certain renal toxins. It is possible that
      there are other markers (unknown), that there are not being analysed, and that can predict
      the kidney damage.

      CONCLUSION In summary, this project focuses on finding a solution to a problem of high
      clinical relevance: to diagnose patients at risk of suffering CIN before CM administration.
      Therefore, it proposes an objective focused on personalized medicine.

      This project will be carried out through the generation of a consortium of professionals from
      different fields, on the one hand researchers, experts in markers of renal damage and on the
      other, clinicians specialized in the realization of vascular catheterizations.
    

Intervention name(s): Early kidney damage biomarkers; Predisposition to kidney injury biomarkers
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): In the urine samples of these patients, a series of biomarkers of early kidney damage and / or predisposition to kidney damage will be measured; In the urine samples of these patients, a series of biomarkers of predisposition to kidney damage will be measured
Other intervention name(s): N-acetyl-beta-D-glucosaminidase (NAG); Kidney Injury Molecule-1 (KIM-1); Neutrophil gelatinase-associated lipocalin (NGAL); Albumin
Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients who will receive an iodinated contrast medium as part of a diagnostic or
        interventional procedure
      
Keywords: Biomarker; Contrast-Media; Nephrotoxicity; Prevention; Diagnosis