<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02237352</url>
  </required_header>
  <id_info>
    <org_study_id>DN-HLV0178-DV</org_study_id>
    <nct_id>NCT02237352</nct_id>
  </id_info>
  <brief_title>Mechanisms of Diabetic Nephropathy in Ecuador</brief_title>
  <official_title>Physiopathogenic Mechanisms Involved in Diabetic Nephropathy, Looking for Prevention and Treatment Solutions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidad Estatal de Milagro</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Secretaría de Ciencia, Tecnología e Innovación (Senescyt)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>PROMETEO</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidad Estatal de Milagro</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prevalence of diabetes mellitus (DM) is increasing worldwide, suggesting that 45% of&#xD;
      diabetics are undiagnosed. DM induces a kidney disease called diabetic nephropathy (DN) which&#xD;
      is the largest single cause of end-stage renal disease and dialysis requirement. In South&#xD;
      America the prevalence of DM and chronic kidney disease has increased, and great disparity&#xD;
      exists among countries in regards to access to the dialysis treatment. It has been&#xD;
      considerate that Hispanic origin increases the risk for DM. The South Americans have&#xD;
      distinctive habits, culture, environment, behavior and genetic background and the factors&#xD;
      involved in DN have not been defined yet. The early kidney lesions such as neoangiogenesis&#xD;
      (pathologic generation of the new blood vessels) and extracellular matrix expansion have been&#xD;
      described. The vascular endothelial growth factor A (VEGF) has been linked to angiogenesis,&#xD;
      but the role of VEGF in DN has not been elucidated yet. VEGF signals mainly through VEGF&#xD;
      receptor 2 (VEGFR2). VEGFR2 interacts with alphaV beta3 integrin (AVB3) in kidney.&#xD;
      Additionally tenascin C is expressed in the extracellular matrix. Tenascin C and the tenascin&#xD;
      C/AVB3 complex have also been linked to angiogenesis, however their roles have not been&#xD;
      unveiled yet in the DN. Investigators hypothesize that VEGF signaling and tenascin C play an&#xD;
      important role in DN and that VEGFR2, AVB3 and tenascin C interact. The purposes of this&#xD;
      study is to characterize social, environmental and biological factors implicated in the DN in&#xD;
      Ecuador and define the role of VEGF signaling and tenascin C in the pathogenesis of the DN.&#xD;
      Investigators propose to study factors involved in DN in diabetic and non-diabetic adults&#xD;
      from general population, with and without DN. In a single time investigators will evaluate&#xD;
      demographics data, habits, personal and family history through a survey. Investigators will&#xD;
      measure anthropometrics parameters and blood pressure; investigators will quantify blood&#xD;
      glucose, glycosylated hemoglobin A1c and proteinuria. In addition investigators will examine&#xD;
      the role of tenascin C and VEGF signaling by analyzing paraffin embedded kidney tissue,&#xD;
      plasma and urine samples. Characterizing the factors involved in the DN from Hispanic people&#xD;
      is key to establish adequate strategies of prevention, diagnosis and treatment in this&#xD;
      population. Furthermore elucidating the role of proteins involved in DN may offer valuable&#xD;
      tools for the development of new treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Determinations of social, environmental and biological factor implicated in diabetic&#xD;
           nephropathy in Ecuador Investigators will study subjects from the general population.&#xD;
           Investigators will contact community and religious leaders in order to invite adult&#xD;
           subjects from the general population to participate in this study and 10000 persons will&#xD;
           be enrolled.&#xD;
&#xD;
           After teaching basic concepts about prevention of diabetic nephropathy in all subjects,&#xD;
           investigators will collect demographics data, house conditions and localization (rural,&#xD;
           urban or around the cities), number of people that share a home, education level,&#xD;
           employment and economical condition, personal health insurance, medical checkup history,&#xD;
           toxic habits (alcohol, cigarette abuse of addictive substances) and physical exercises&#xD;
           habits. Investigators will collect personal and family antecedent of diabetes mellitus,&#xD;
           diabetic nephropathy, hypertension, kidney diseases, diabetes gestational, current&#xD;
           treatments and other chronic diseases. Investigators will measure body weight (Kg),&#xD;
           height (m) and investigators will calculate body mass index. Investigators will also&#xD;
           measure blood pressure, blood glucose, glycosylated hemoglobin, microalbuminuria and&#xD;
           proteinuria. Trained personnel will fill out the person's survey. Investigators will&#xD;
           supervise and collect data from 2% of the sample.&#xD;
&#xD;
        2. Role of extracellular matrix proteins and growth factors signaling in diabetic&#xD;
           nephropathy&#xD;
&#xD;
             1. Systemic and urine studies: proteins involved in diabetic nephropathy pathogenesis&#xD;
                as vascular endothelial factor A (VEGF) and extracellular matrix protein as&#xD;
                tenascin C (tenascin) concentration will be measured by a commercially available&#xD;
                kits in plasma and urine (respectively). Samples will be obtained from diabetics&#xD;
                with (n: 20) and without diabetic nephropathy (n: 20) and from non-diabetic&#xD;
                subjects (controls) from the general population (n: 2000). Determinations of&#xD;
                social, environmental and biological factor will be completed as in aim 1.&#xD;
&#xD;
             2. Kidney tissue studies: investigators will determine the role of protein involved in&#xD;
                diabetic nephropathy, VEGF signaling and tenascin in:&#xD;
&#xD;
      I) Paraffin embedded kidney tissue obtained from the sample libraries of pathology&#xD;
      laboratories will be studied. Slides from non-diabetics (n: 10) and diabetics with diabetic&#xD;
      nephropathy (n: 20) and without diabetic nephropathy (n: 10) will be collected. The role of&#xD;
      proteins involved in diabetic nephropathy as VEGF signaling and tenascin will be studied by&#xD;
      immunohistochemistry and proximity link assay.&#xD;
&#xD;
      II) Paraffin embedded kidney slides from diabetics with diabetic nephropathy (n: 12),&#xD;
      non-diabetic control (n: 6) with primary glomerulopathy as minimal change disease, and&#xD;
      diabetic controls without diabetic nephropathy (n: 6), will be studied. Investigators will&#xD;
      recruit patients with kidney biopsy indicated, and scheduled to be performed, by their&#xD;
      medical doctors. After pathology diagnosis completion, some of the remnant paraffin embedded&#xD;
      tissue will be used for this study. The role of proteins involved in diabetic nephropathy,&#xD;
      VEGF signaling and tenascin will be studied by immunohistochemistry and proximity link assay.&#xD;
      Urine and plasma will be collected prior to the kidney biopsy in order to measure protein&#xD;
      concentration of potentially useful biomarkers of diabetic nephropathy; VEGF and tenascin&#xD;
      levels will be quantified. Patients will be informed and signed consent will be required.&#xD;
&#xD;
      Blood glucose will be measured by the blood glucose meter and test strip. Glycosylated&#xD;
      hemoglobin A1c and microalbuminuria (albumin/creatinine in spot urine) will be quantified&#xD;
      using the portable machine (Siemens).&#xD;
&#xD;
      In fasting conditions investigators will consider normal blood glucose values &lt;99 mg%,&#xD;
      pre-diabetes between 100 and 125 mg% and diabetes ≥126 mg%. In non-fasting conditions values&#xD;
      of blood glucose &gt;200mg% will be considered as diabetes. Investigators will deem normal&#xD;
      glycosylated A1c hemoglobin values &lt;5.6 %, pre-diabetes between 5.7 and 6.4% and diabetes&#xD;
      ≥6.5%.&#xD;
&#xD;
      Investigators will deem normal albuminuria values of albumin/creatinine ratio &lt;29mg/g,&#xD;
      microalbuminuria values between 30 and 299 mg/g and macro-albuminuria values ≥300mg/g.&#xD;
      Proteinuria will also be evaluated by reactive urine strips.&#xD;
&#xD;
      In the case of inconsistent results or out of range values the analysis will be repeated in&#xD;
      the same sample or re analyzed by standard laboratory equipment and techniques.&#xD;
&#xD;
      Investigators will consider diabetic nephropathy as persistent proteinuria associated to&#xD;
      diabetic retinopathy and decreased endogen glomerular filtration rate (in subjects without a&#xD;
      diagnosis of other kidney or urinary tract diseases). In Type 1 diabetics, diabetic&#xD;
      nephropathy will be diagnosed if the history of diabetes is longer than 10 years prior to the&#xD;
      onset of proteinuria; in diabetic type 2, proteinuria associated to a decreased glomerular&#xD;
      filtration rate at diagnosis time, investigators will deem diabetic nephropathy.&#xD;
&#xD;
      In all paraffin embedded kidney samples we will measure the protein expression and&#xD;
      localization. Investigators will use kits, primary and secondary antibodies commercially&#xD;
      available to perform immunohistochemistry and proximity link assay. Investigators will&#xD;
      perform those experiments in cooperation with pathologist.&#xD;
&#xD;
      All subjects recruited from general population will be identified by a unique code. Number&#xD;
      and capital letters code will be placed in the survey and in the sample labels as M0001 (M:&#xD;
      city, number 0001: person number 0001). Data will be uploaded and saved in a secure data&#xD;
      base. Trained personnel will be in charge of handling the data base. Investigators will&#xD;
      supervise the data entry. An investigator at least once every 6 months will randomly select&#xD;
      2% survey and will match it against the information uploaded in the database. Furthermore,&#xD;
      investigators will analyze and report all collected data from the surveys even if they are&#xD;
      incomplete by adjusting the analysis parameters of the incomplete ones.&#xD;
&#xD;
      Investigators will use descriptive statistic tools to describe groups (mean, standard&#xD;
      deviation and standard error or median and interquartile range). For group comparisons,&#xD;
      unpaired T test, Mann Whitney or Fisher's test will be used. ANOVA, Kruskal Wallis and Chi&#xD;
      Square test will be performed for to compare unmatched groups; to quantify association&#xD;
      between two variables Pearson and Spearman correlation test will be used. Simple or multiple&#xD;
      regressions will be considered to predict value from variables. P value &lt;0.05 will be deemed&#xD;
      significant. A sample from the general population was calculated considering the adult&#xD;
      population between 21-70 years old in Ecuador.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">September 15, 2014</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <target_duration>1 Day</target_duration>
  <primary_outcome>
    <measure>House localization</measure>
    <time_frame>up to 12 month</time_frame>
    <description>House localization (rural, urban or around the cities) in 2000 persons</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Protein expression</measure>
    <time_frame>up to 24 month</time_frame>
    <description>Protein expression in 1000 persons</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Education level</measure>
    <time_frame>up 12 month</time_frame>
    <description>Education level (primary school, secondary school, university) in 2000 persons.</description>
  </other_outcome>
  <other_outcome>
    <measure>Employment</measure>
    <time_frame>up to 12 month</time_frame>
    <description>Employment conditions in 2000 persons.</description>
  </other_outcome>
  <other_outcome>
    <measure>Health insurance coverage</measure>
    <time_frame>12 month</time_frame>
    <description>Personal health insurance coverage in 2000 persons.</description>
  </other_outcome>
  <other_outcome>
    <measure>Smoking habit</measure>
    <time_frame>up to 12 month</time_frame>
    <description>Smoking habit in 2000 persons.</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical exercises habits.</measure>
    <time_frame>upt to 12 month</time_frame>
    <description>Physical exercises habits in 2000 persons.</description>
  </other_outcome>
  <other_outcome>
    <measure>Personal and family antecedent of diabetes mellitus</measure>
    <time_frame>up to 12 month</time_frame>
    <description>Personal and family antecedent of diabetes mellitus in 2000 persons</description>
  </other_outcome>
  <other_outcome>
    <measure>Personal and family antecedent of kidney diseases</measure>
    <time_frame>up to 12 month</time_frame>
    <description>Personal and family antecedent of kidney diseases in 2000 persons</description>
  </other_outcome>
  <other_outcome>
    <measure>Body mass index</measure>
    <time_frame>up to 12 month</time_frame>
    <description>Body mass index evaluation in 2000 persons</description>
  </other_outcome>
  <other_outcome>
    <measure>Systolic pressure</measure>
    <time_frame>12 month</time_frame>
    <description>Systolic pressure evaluation in 2000 persons</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood glucose</measure>
    <time_frame>up 12 month</time_frame>
    <description>Blood glucose evaluation in 2000 persons</description>
  </other_outcome>
  <other_outcome>
    <measure>Albuminuria</measure>
    <time_frame>up to 12 month</time_frame>
    <description>Albuminuria evaluation in 2000 persons</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">10064</enrollment>
  <condition>Diabetic Nephropathy</condition>
  <condition>Diabetes Mellitus</condition>
  <condition>Kidney Diseases</condition>
  <condition>Diabetic Kidney Disease</condition>
  <condition>Chronic Kidney Disease</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>Subjects without diabetic nephropathy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic nephropathy</arm_group_label>
    <description>Subjects with diabetic nephropathy</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma and urine.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Community sample (general healthy population and diabetics subjects), and patients with and&#xD;
        without diabetic nephropathy evaluated at Hospital Luis Vernaza&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adults,&#xD;
&#xD;
          -  age between 21 and 70 years old,&#xD;
&#xD;
          -  persons able to sign informed consent,&#xD;
&#xD;
          -  diabetics without diabetic nephropathy,&#xD;
&#xD;
          -  diabetic with diabetic nephropathy,&#xD;
&#xD;
          -  not hospitalized,&#xD;
&#xD;
          -  not suffering acute disease,&#xD;
&#xD;
          -  living in their home for at least 6 months before to be contacted.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  subjects with acute diseases,&#xD;
&#xD;
          -  subjects with not metabolic compensation,&#xD;
&#xD;
          -  persons temporarily residing in the place of contact,&#xD;
&#xD;
          -  younger than 21 years old,&#xD;
&#xD;
          -  older than 70 years old.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Delma Veron, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidad Estatal de Milagro</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UNEMI, Universidad Estatal de Milagro, Facultad de Ciencias de la Salud</name>
      <address>
        <city>Milagro</city>
        <state>Guayas</state>
        <zip>091050</zip>
        <country>Ecuador</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ecuador</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>November 2, 2020</last_update_submitted>
  <last_update_submitted_qc>November 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes mellitus</keyword>
  <keyword>Diabetic nephropathy</keyword>
  <keyword>Social Factors</keyword>
  <keyword>Biological Factors</keyword>
  <keyword>VEGF-A</keyword>
  <keyword>Tenascin C</keyword>
  <keyword>Disease characterization</keyword>
  <keyword>Mechanisms</keyword>
  <keyword>Kidney</keyword>
  <keyword>Chronic kidney disease</keyword>
  <keyword>Secondary nephropathy</keyword>
  <keyword>South America</keyword>
  <keyword>Hispanics</keyword>
  <keyword>Ecuador</keyword>
  <keyword>Biomarkers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Diabetic Nephropathies</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02237352
org study id: DN-HLV0178-DV
nct id: NCT02237352
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The prevalence of diabetes mellitus (DM) is increasing worldwide, suggesting that 45% of
      diabetics are undiagnosed. DM induces a kidney disease called diabetic nephropathy (DN) which
      is the largest single cause of end-stage renal disease and dialysis requirement. In South
      America the prevalence of DM and chronic kidney disease has increased, and great disparity
      exists among countries in regards to access to the dialysis treatment. It has been
      considerate that Hispanic origin increases the risk for DM. The South Americans have
      distinctive habits, culture, environment, behavior and genetic background and the factors
      involved in DN have not been defined yet. The early kidney lesions such as neoangiogenesis
      (pathologic generation of the new blood vessels) and extracellular matrix expansion have been
      described. The vascular endothelial growth factor A (VEGF) has been linked to angiogenesis,
      but the role of VEGF in DN has not been elucidated yet. VEGF signals mainly through VEGF
      receptor 2 (VEGFR2). VEGFR2 interacts with alphaV beta3 integrin (AVB3) in kidney.
      Additionally tenascin C is expressed in the extracellular matrix. Tenascin C and the tenascin
      C/AVB3 complex have also been linked to angiogenesis, however their roles have not been
      unveiled yet in the DN. Investigators hypothesize that VEGF signaling and tenascin C play an
      important role in DN and that VEGFR2, AVB3 and tenascin C interact. The purposes of this
      study is to characterize social, environmental and biological factors implicated in the DN in
      Ecuador and define the role of VEGF signaling and tenascin C in the pathogenesis of the DN.
      Investigators propose to study factors involved in DN in diabetic and non-diabetic adults
      from general population, with and without DN. In a single time investigators will evaluate
      demographics data, habits, personal and family history through a survey. Investigators will
      measure anthropometrics parameters and blood pressure; investigators will quantify blood
      glucose, glycosylated hemoglobin A1c and proteinuria. In addition investigators will examine
      the role of tenascin C and VEGF signaling by analyzing paraffin embedded kidney tissue,
      plasma and urine samples. Characterizing the factors involved in the DN from Hispanic people
      is key to establish adequate strategies of prevention, diagnosis and treatment in this
      population. Furthermore elucidating the role of proteins involved in DN may offer valuable
      tools for the development of new treatments.
1. Determinations of social, environmental and biological factor implicated in diabetic
           nephropathy in Ecuador Investigators will study subjects from the general population.
           Investigators will contact community and religious leaders in order to invite adult
           subjects from the general population to participate in this study and 10000 persons will
           be enrolled.

           After teaching basic concepts about prevention of diabetic nephropathy in all subjects,
           investigators will collect demographics data, house conditions and localization (rural,
           urban or around the cities), number of people that share a home, education level,
           employment and economical condition, personal health insurance, medical checkup history,
           toxic habits (alcohol, cigarette abuse of addictive substances) and physical exercises
           habits. Investigators will collect personal and family antecedent of diabetes mellitus,
           diabetic nephropathy, hypertension, kidney diseases, diabetes gestational, current
           treatments and other chronic diseases. Investigators will measure body weight (Kg),
           height (m) and investigators will calculate body mass index. Investigators will also
           measure blood pressure, blood glucose, glycosylated hemoglobin, microalbuminuria and
           proteinuria. Trained personnel will fill out the person's survey. Investigators will
           supervise and collect data from 2% of the sample.

        2. Role of extracellular matrix proteins and growth factors signaling in diabetic
           nephropathy

             1. Systemic and urine studies: proteins involved in diabetic nephropathy pathogenesis
                as vascular endothelial factor A (VEGF) and extracellular matrix protein as
                tenascin C (tenascin) concentration will be measured by a commercially available
                kits in plasma and urine (respectively). Samples will be obtained from diabetics
                with (n: 20) and without diabetic nephropathy (n: 20) and from non-diabetic
                subjects (controls) from the general population (n: 2000). Determinations of
                social, environmental and biological factor will be completed as in aim 1.

             2. Kidney tissue studies: investigators will determine the role of protein involved in
                diabetic nephropathy, VEGF signaling and tenascin in:

      I) Paraffin embedded kidney tissue obtained from the sample libraries of pathology
      laboratories will be studied. Slides from non-diabetics (n: 10) and diabetics with diabetic
      nephropathy (n: 20) and without diabetic nephropathy (n: 10) will be collected. The role of
      proteins involved in diabetic nephropathy as VEGF signaling and tenascin will be studied by
      immunohistochemistry and proximity link assay.

      II) Paraffin embedded kidney slides from diabetics with diabetic nephropathy (n: 12),
      non-diabetic control (n: 6) with primary glomerulopathy as minimal change disease, and
      diabetic controls without diabetic nephropathy (n: 6), will be studied. Investigators will
      recruit patients with kidney biopsy indicated, and scheduled to be performed, by their
      medical doctors. After pathology diagnosis completion, some of the remnant paraffin embedded
      tissue will be used for this study. The role of proteins involved in diabetic nephropathy,
      VEGF signaling and tenascin will be studied by immunohistochemistry and proximity link assay.
      Urine and plasma will be collected prior to the kidney biopsy in order to measure protein
      concentration of potentially useful biomarkers of diabetic nephropathy; VEGF and tenascin
      levels will be quantified. Patients will be informed and signed consent will be required.

      Blood glucose will be measured by the blood glucose meter and test strip. Glycosylated
      hemoglobin A1c and microalbuminuria (albumin/creatinine in spot urine) will be quantified
      using the portable machine (Siemens).

      In fasting conditions investigators will consider normal blood glucose values <99 mg%,
      pre-diabetes between 100 and 125 mg% and diabetes ≥126 mg%. In non-fasting conditions values
      of blood glucose >200mg% will be considered as diabetes. Investigators will deem normal
      glycosylated A1c hemoglobin values <5.6 %, pre-diabetes between 5.7 and 6.4% and diabetes
      ≥6.5%.

      Investigators will deem normal albuminuria values of albumin/creatinine ratio <29mg/g,
      microalbuminuria values between 30 and 299 mg/g and macro-albuminuria values ≥300mg/g.
      Proteinuria will also be evaluated by reactive urine strips.

      In the case of inconsistent results or out of range values the analysis will be repeated in
      the same sample or re analyzed by standard laboratory equipment and techniques.

      Investigators will consider diabetic nephropathy as persistent proteinuria associated to
      diabetic retinopathy and decreased endogen glomerular filtration rate (in subjects without a
      diagnosis of other kidney or urinary tract diseases). In Type 1 diabetics, diabetic
      nephropathy will be diagnosed if the history of diabetes is longer than 10 years prior to the
      onset of proteinuria; in diabetic type 2, proteinuria associated to a decreased glomerular
      filtration rate at diagnosis time, investigators will deem diabetic nephropathy.

      In all paraffin embedded kidney samples we will measure the protein expression and
      localization. Investigators will use kits, primary and secondary antibodies commercially
      available to perform immunohistochemistry and proximity link assay. Investigators will
      perform those experiments in cooperation with pathologist.

      All subjects recruited from general population will be identified by a unique code. Number
      and capital letters code will be placed in the survey and in the sample labels as M0001 (M:
      city, number 0001: person number 0001). Data will be uploaded and saved in a secure data
      base. Trained personnel will be in charge of handling the data base. Investigators will
      supervise the data entry. An investigator at least once every 6 months will randomly select
      2% survey and will match it against the information uploaded in the database. Furthermore,
      investigators will analyze and report all collected data from the surveys even if they are
      incomplete by adjusting the analysis parameters of the incomplete ones.

      Investigators will use descriptive statistic tools to describe groups (mean, standard
      deviation and standard error or median and interquartile range). For group comparisons,
      unpaired T test, Mann Whitney or Fisher's test will be used. ANOVA, Kruskal Wallis and Chi
      Square test will be performed for to compare unmatched groups; to quantify association
      between two variables Pearson and Spearman correlation test will be used. Simple or multiple
      regressions will be considered to predict value from variables. P value <0.05 will be deemed
      significant. A sample from the general population was calculated considering the adult
      population between 21-70 years old in Ecuador.
observational model: Case-Control
time perspective: Cross-Sectional
measure: House localization
time frame: up to 12 month
description: House localization (rural, urban or around the cities) in 2000 persons
measure: Protein expression
time frame: up to 24 month
description: Protein expression in 1000 persons
measure: Education level
time frame: up 12 month
description: Education level (primary school, secondary school, university) in 2000 persons.
measure: Employment
time frame: up to 12 month
description: Employment conditions in 2000 persons.
measure: Health insurance coverage
time frame: 12 month
description: Personal health insurance coverage in 2000 persons.
measure: Smoking habit
time frame: up to 12 month
description: Smoking habit in 2000 persons.
measure: Physical exercises habits.
time frame: upt to 12 month
description: Physical exercises habits in 2000 persons.
measure: Personal and family antecedent of diabetes mellitus
time frame: up to 12 month
description: Personal and family antecedent of diabetes mellitus in 2000 persons
measure: Personal and family antecedent of kidney diseases
time frame: up to 12 month
description: Personal and family antecedent of kidney diseases in 2000 persons
measure: Body mass index
time frame: up to 12 month
description: Body mass index evaluation in 2000 persons
measure: Systolic pressure
time frame: 12 month
description: Systolic pressure evaluation in 2000 persons
measure: Blood glucose
time frame: up 12 month
description: Blood glucose evaluation in 2000 persons
measure: Albuminuria
time frame: up to 12 month
description: Albuminuria evaluation in 2000 persons
arm group label: Control
description: Subjects without diabetic nephropathy
arm group label: Diabetic nephropathy
description: Subjects with diabetic nephropathy
Plasma and urine.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Delma Veron, MD PhD
role: Principal Investigator
affiliation: Universidad Estatal de Milagro
facility: 
country: Ecuador
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Diabetic Nephropathies
mesh term: Diabetes Mellitus
sharing ipd: Undecided