<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/NCT03272854</url>
  </required_header>
  <id_info>
    <org_study_id>METc2001/039</org_study_id>
    <nct_id>NCT03272854</nct_id>
  </id_info>
  <brief_title>TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study</brief_title>
  <acronym>TxL-IRI</acronym>
  <official_title>TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medical Center Groningen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Short-term (1-year) results of renal transplantation are now excellent (over 95%). Long-term&#xD;
      (10-year and longer) results are, however, still disappointing. Where most research has&#xD;
      focused on immunosuppression and infections, the investigators hypothesize that in renal&#xD;
      transplant recipient, amongst others overweight, obesity, chronic use of immunosuppressive&#xD;
      drugs and impaired renal function contribute to insulin resistance and chronic low-grade&#xD;
      inflammation, which pose the renal transplant recipients at increased risk for cardiovascular&#xD;
      disease, decline of function of the transplanted kidney and other complications, including&#xD;
      post-transplant diabetes. This study is a biobank and cohort study which investigates this&#xD;
      hypothesis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Short-term (1-year) results of renal transplantation are now excellent (over 95%). Long-term&#xD;
      (10-year and longer) results are, however, still disappointing. Where most research has&#xD;
      focused on immunosuppression and infections, the investigators hypothesize that in renal&#xD;
      transplant recipient, amongst others overweight, obesity, chronic use of immunosuppressive&#xD;
      drugs and impaired renal function contribute to insulin resistance and chronic low-grade&#xD;
      inflammation, which pose the renal transplant recipients at increased risk for cardiovascular&#xD;
      disease, decline of function of the transplanted kidney and other complications, including&#xD;
      post-transplant diabetes. To investigate this hypothesis we have detailedly phenotyped 606&#xD;
      renal transplant recipients who at the time of inclusion all were one year or more after&#xD;
      transplantation, therewith providing a representation of stable outpatient renal trannsplant&#xD;
      recipients late after renal transplantation. At the time of these baseline measurements, we&#xD;
      also created a biobank with plasma, serum and aliquots of 24h urine collections. Beyond&#xD;
      baseline, we have a regular update on adverse events, including all-cause mortality,&#xD;
      cause-specific mortality, graft failure and development of new-onset diabetes after&#xD;
      transplantation (NODAT).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 2001</start_date>
  <completion_date type="Anticipated">August 2031</completion_date>
  <primary_completion_date type="Actual">July 2003</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>30 Years</target_duration>
  <primary_outcome>
    <measure>All-Cause Mortality</measure>
    <time_frame>30 years</time_frame>
    <description>All-Cause Mortality</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Graft Failure</measure>
    <time_frame>30 years</time_frame>
    <description>Death-Censored Graft Failure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>New Onset Diabetes After Transplantation</measure>
    <time_frame>30 years</time_frame>
    <description>NODAT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular Mortality</measure>
    <time_frame>30 years</time_frame>
    <description>Cause-Specific Mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-Cardiovascular Mortality</measure>
    <time_frame>30 years</time_frame>
    <description>Cause-Specific Mortality</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Venous Thrombosis</measure>
    <time_frame>30 years</time_frame>
    <description>Venous Thrombosis</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">606</enrollment>
  <condition>Death</condition>
  <condition>Graft Failure</condition>
  <condition>Death, Cardiac</condition>
  <condition>Diabetes</condition>
  <arm_group>
    <arm_group_label>Renal Transplant Recipients</arm_group_label>
    <description>A cohort or renal transplant recipients, all more than 1 year after transplantation at inclusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention performed, the study is observational</intervention_name>
    <arm_group_label>Renal Transplant Recipients</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      EDTA plasma, serum, aliquots of 24h urine collections all stored at -80 degrees Centigrade.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Stable outpatient renal transplant recipients more than 1 year after transplantation,&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  More than one year after renal transplantation&#xD;
&#xD;
          -  History of renal transplantation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Signs of active infection&#xD;
&#xD;
          -  Signs of active cardiac decompensation&#xD;
&#xD;
          -  Active malignancy other than skin cancer&#xD;
&#xD;
          -  Prognosis &lt; 1 year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephan JL Bakker, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center Groningen</affiliation>
  </overall_official>
  <results_reference>
    <citation>de Vries AP, Bakker SJ, van Son WJ, van der Heide JJ, Ploeg RJ, The HT, de Jong PE, Gans RO. Metabolic syndrome is associated with impaired long-term renal allograft function; not all component criteria contribute equally. Am J Transplant. 2004 Oct;4(10):1675-83. doi: 10.1111/j.1600-6143.2004.00558.x.</citation>
    <PMID>15367224</PMID>
  </results_reference>
  <results_reference>
    <citation>van Ree RM, de Vries AP, Oterdoom LH, The TH, Gansevoort RT, Homan van der Heide JJ, van Son WJ, Ploeg RJ, de Jong PE, Gans RO, Bakker SJ. Abdominal obesity and smoking are important determinants of C-reactive protein in renal transplant recipients. Nephrol Dial Transplant. 2005 Nov;20(11):2524-31. doi: 10.1093/ndt/gfi052. Epub 2005 Aug 22.</citation>
    <PMID>16115856</PMID>
  </results_reference>
  <results_reference>
    <citation>Oterdoom LH, de Vries AP, van Son WJ, van der Heide JJ, Ploeg RJ, Gansevoort RT, de Jong PE, Gans RO, Bakker SJ. Validation of insulin resistance indexes in a stable renal transplant population. Diabetes Care. 2005 Oct;28(10):2424-9. doi: 10.2337/diacare.28.10.2424.</citation>
    <PMID>16186274</PMID>
  </results_reference>
  <results_reference>
    <citation>Hartog JW, de Vries AP, Bakker SJ, Graaff R, van Son WJ, van der Heide JJ, Gans RO, Wolffenbuttel BH, de Jong PE, Smit AJ. Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients. Nephrol Dial Transplant. 2006 Aug;21(8):2263-9. doi: 10.1093/ndt/gfl132. Epub 2006 Apr 5.</citation>
    <PMID>16597636</PMID>
  </results_reference>
  <results_reference>
    <citation>van Ree RM, Oterdoom LH, de Vries AP, Gansevoort RT, van der Heide JJ, van Son WJ, Ploeg RJ, de Jong PE, Gans RO, Bakker SJ. Elevated levels of C-reactive protein independently predict accelerated deterioration of graft function in renal transplant recipients. Nephrol Dial Transplant. 2007 Jan;22(1):246-53. doi: 10.1093/ndt/gfl511. Epub 2006 Sep 23.</citation>
    <PMID>16998222</PMID>
  </results_reference>
  <results_reference>
    <citation>Oterdoom LH, de Vries AP, Gansevoort RT, van Son WJ, van der Heide JJ, Ploeg RJ, de Jong PE, Gans RO, Bakker SJ. Determinants of insulin resistance in renal transplant recipients. Transplantation. 2007 Jan 15;83(1):29-35. doi: 10.1097/01.tp.0000245844.27683.48.</citation>
    <PMID>17220787</PMID>
  </results_reference>
  <results_reference>
    <citation>Oterdoom LH, de Vries AP, Gansevoort RT, de Jong PE, Gans RO, Bakker SJ. Fasting insulin modifies the relation between age and renal function. Nephrol Dial Transplant. 2007 Jun;22(6):1587-92. doi: 10.1093/ndt/gfm037. Epub 2007 Feb 21.</citation>
    <PMID>17314207</PMID>
  </results_reference>
  <results_reference>
    <citation>Gross S, van Ree RM, Oterdoom LH, de Vries AP, van Son WJ, de Jong PE, Navis GJ, Zuurman MW, Bierhaus A, Gans RO, Bakker SJ. Low levels of sRAGE are associated with increased risk for mortality in renal transplant recipients. Transplantation. 2007 Sep 15;84(5):659-63. doi: 10.1097/01.tp.0000280556.16275.2a.</citation>
    <PMID>17876282</PMID>
  </results_reference>
  <results_reference>
    <citation>van Timmeren MM, Vaidya VS, van Ree RM, Oterdoom LH, de Vries AP, Gans RO, van Goor H, Stegeman CA, Bonventre JV, Bakker SJ. High urinary excretion of kidney injury molecule-1 is an independent predictor of graft loss in renal transplant recipients. Transplantation. 2007 Dec 27;84(12):1625-30. doi: 10.1097/01.tp.0000295982.78039.ef.</citation>
    <PMID>18165774</PMID>
  </results_reference>
  <results_reference>
    <citation>Lijfering WM, de Vries AP, Veeger NJ, van Son WJ, Bakker SJ, van der Meer J. Possible contribution of cytomegalovirus infection to the high risk of (recurrent) venous thrombosis after renal transplantation. Thromb Haemost. 2008 Jan;99(1):127-32. doi: 10.1160/TH07-05-0340.</citation>
    <PMID>18217144</PMID>
  </results_reference>
  <results_reference>
    <citation>Oterdoom LH, van Ree RM, de Vries AP, Gansevoort RT, Schouten JP, van Son WJ, Homan van der Heide JJ, Navis G, de Jong PE, Gans RO, Bakker SJ. Urinary creatinine excretion reflecting muscle mass is a predictor of mortality and graft loss in renal transplant recipients. Transplantation. 2008 Aug 15;86(3):391-8. doi: 10.1097/TP.0b013e3181788aea.</citation>
    <PMID>18698241</PMID>
  </results_reference>
  <results_reference>
    <citation>van Ree RM, Oterdoom LH, de Vries AP, Homan van der Heide JJ, van Son WJ, Navis G, Gans RO, Bakker SJ. Circulating markers of endothelial dysfunction interact with proteinuria in predicting mortality in renal transplant recipients. Transplantation. 2008 Dec 27;86(12):1713-9. doi: 10.1097/TP.0b013e3181903d25.</citation>
    <PMID>19104410</PMID>
  </results_reference>
  <results_reference>
    <citation>Hartog JW, Gross S, Oterdoom LH, van Ree RM, de Vries AP, Smit AJ, Schouten JP, Nawroth PP, Gans RO, van Son WJ, Bierhaus A, Bakker SJ. Skin-autofluorescence is an independent predictor of graft loss in renal transplant recipients. Transplantation. 2009 Apr 15;87(7):1069-77. doi: 10.1097/TP.0b013e31819d3173.</citation>
    <PMID>19352130</PMID>
  </results_reference>
  <results_reference>
    <citation>Oterdoom LH, de Vries AP, van Ree RM, Gansevoort RT, van Son WJ, van der Heide JJ, Navis G, de Jong PE, Gans RO, Bakker SJ. N-terminal pro-B-type natriuretic peptide and mortality in renal transplant recipients versus the general population. Transplantation. 2009 May 27;87(10):1562-70. doi: 10.1097/TP.0b013e3181a4bb80.</citation>
    <PMID>19461495</PMID>
  </results_reference>
  <results_reference>
    <citation>van Ree RM, de Vries AP, Oterdoom LH, Seelen MA, Gansevoort RT, Schouten JP, Struck J, Navis G, Gans RO, van der Heide JJ, van Son WJ, Bakker SJ. Plasma procalcitonin is an independent predictor of graft failure late after renal transplantation. Transplantation. 2009 Jul 27;88(2):279-87. doi: 10.1097/TP.0b013e3181ac9ea0.</citation>
    <PMID>19623026</PMID>
  </results_reference>
  <results_reference>
    <citation>van Ree RM, de Vries AP, Zelle DM, de Vries LV, Oterdoom LH, Gans RO, Schouten JP, Lems SP, van Son WJ, Bakker SJ. Latent cytomegalovirus infection is an independent risk factor for late graft failure in renal transplant recipients. Med Sci Monit. 2011 Nov;17(11):CR609-617. doi: 10.12659/msm.882045.</citation>
    <PMID>22037739</PMID>
  </results_reference>
  <results_reference>
    <citation>Said MY, Deetman PE, de Vries AP, Zelle DM, Gans RO, Navis G, Joosten MM, Bakker SJ. Causal path analyses of the association of protein intake with risk of mortality and graft failure in renal transplant recipients. Clin Transplant. 2015 May;29(5):447-57. doi: 10.1111/ctr.12536. Epub 2015 Apr 23.</citation>
    <PMID>25739949</PMID>
  </results_reference>
  <results_reference>
    <citation>Eisenga MF, Dullaart RP, Berger SP, Sloan JH, de Vries AP, Bakker SJ, Gaillard CA. Association of hepcidin-25 with survival after kidney transplantation. Eur J Clin Invest. 2016 Dec;46(12):994-1001. doi: 10.1111/eci.12682. Epub 2016 Oct 26.</citation>
    <PMID>27696386</PMID>
  </results_reference>
  <results_reference>
    <citation>Adepu S, Katta K, Tietge UJ, Kwakernaak AJ, Dam W, van Goor H, Dullaart RP, Navis GJ, Bakker SJ, van den Born J. Hepatic syndecan-1 changes associate with dyslipidemia after renal transplantation. Am J Transplant. 2014 Oct;14(10):2328-38. doi: 10.1111/ajt.12842. Epub 2014 Aug 25.</citation>
    <PMID>25154787</PMID>
  </results_reference>
  <results_reference>
    <citation>Annema W, Dikkers A, de Boer JF, Dullaart RP, Sanders JS, Bakker SJ, Tietge UJ. HDL Cholesterol Efflux Predicts Graft Failure in Renal Transplant Recipients. J Am Soc Nephrol. 2016 Feb;27(2):595-603. doi: 10.1681/ASN.2014090857. Epub 2015 Aug 28.</citation>
    <PMID>26319244</PMID>
  </results_reference>
  <results_reference>
    <citation>Leberkuhne LJ, Ebtehaj S, Dimova LG, Dikkers A, Dullaart RP, Bakker SJ, Tietge UJ. The predictive value of the antioxidative function of HDL for cardiovascular disease and graft failure in renal transplant recipients. Atherosclerosis. 2016 Jun;249:181-5. doi: 10.1016/j.atherosclerosis.2016.04.008. Epub 2016 Apr 8.</citation>
    <PMID>27107804</PMID>
  </results_reference>
  <results_reference>
    <citation>Eisenga MF, Zelle DM, Sloan JH, Gaillard CAJM, Bakker SJL, Dullaart RPF. High Serum PCSK9 Is Associated With Increased Risk of New-Onset Diabetes After Transplantation in Renal Transplant Recipients. Diabetes Care. 2017 Jul;40(7):894-901. doi: 10.2337/dc16-2258. Epub 2017 May 1.</citation>
    <PMID>28461454</PMID>
  </results_reference>
  <results_reference>
    <citation>Eisenga MF, Dullaart RPF, Berger SP, Touw DJ, Bakker SJL, Gaillard CAJM. Urinary prednisolone excretion is a determinant of serum hepcidin levels in renal transplant recipients. Am J Hematol. 2017 Aug;92(8):E173-E175. doi: 10.1002/ajh.24785. Epub 2017 Jun 9. No abstract available.</citation>
    <PMID>28494514</PMID>
  </results_reference>
  <results_reference>
    <citation>Sotomayor CG, Eisenga MF, Gomes Neto AW, Ozyilmaz A, Gans ROB, Jong WHA, Zelle DM, Berger SP, Gaillard CAJM, Navis GJ, Bakker SJ. Vitamin C Depletion and All-Cause Mortality in Renal Transplant Recipients. Nutrients. 2017 Jun 2;9(6):568. doi: 10.3390/nu9060568.</citation>
    <PMID>28574431</PMID>
  </results_reference>
  <results_reference>
    <citation>van Timmeren MM, Lems SP, Hepkema BG, Bakker SJ. Anti-human leukocyte antigen antibodies and development of graft failure after renal transplantation. Transplantation. 2009 Dec 27;88(12):1399-400. doi: 10.1097/TP.0b013e3181bc3ef0. No abstract available.</citation>
    <PMID>20029338</PMID>
  </results_reference>
  <results_reference>
    <citation>Zelle DM, Corpeleijn E, van Ree RM, Stolk RP, van der Veer E, Gans RO, Homan van der Heide JJ, Navis G, Bakker SJ. Markers of the hepatic component of the metabolic syndrome as predictors of mortality in renal transplant recipients. Am J Transplant. 2010 Jan;10(1):106-14. doi: 10.1111/j.1600-6143.2009.02876.x. Epub 2009 Nov 24.</citation>
    <PMID>19951280</PMID>
  </results_reference>
  <results_reference>
    <citation>van Ree RM, Gross S, Zelle DM, van der Heide JJ, Schouten JP, van Son WJ, Gans RO, Bakker SJ. Influence of C-reactive protein and urinary protein excretion on prediction of graft failure and mortality by serum albumin in renal transplant recipients. Transplantation. 2010 May 27;89(10):1247-54. doi: 10.1097/TP.0b013e3181d720e3.</citation>
    <PMID>20559032</PMID>
  </results_reference>
  <results_reference>
    <citation>Zelle DM, Corpeleijn E, Stolk RP, de Greef MH, Gans RO, van der Heide JJ, Navis G, Bakker SJ. Low physical activity and risk of cardiovascular and all-cause mortality in renal transplant recipients. Clin J Am Soc Nephrol. 2011 Apr;6(4):898-905. doi: 10.2215/CJN.03340410. Epub 2011 Mar 3.</citation>
    <PMID>21372213</PMID>
  </results_reference>
  <results_reference>
    <citation>Agarwal PK, Hellemons ME, Zelle DM, van Ree RM, van den Born J, van der Heide JJ, Gans RO, van Son WJ, Navis G, Bakker SJ. Smoking is a risk factor for graft failure and mortality after renal transplantation. Am J Nephrol. 2011;34(1):26-31. doi: 10.1159/000328903. Epub 2011 Jun 9.</citation>
    <PMID>21659736</PMID>
  </results_reference>
  <results_reference>
    <citation>Zelle DM, Agarwal PK, Ramirez JL, van der Heide JJ, Corpeleijn E, Gans RO, Navis G, Bakker SJ. Alcohol consumption, new onset of diabetes after transplantation, and all-cause mortality in renal transplant recipients. Transplantation. 2011 Jul 27;92(2):203-9. doi: 10.1097/TP.0b013e318222ca10.</citation>
    <PMID>21685828</PMID>
  </results_reference>
  <results_reference>
    <citation>Sinkeler SJ, Zelle DM, Homan van der Heide JJ, Gans RO, Navis G, Bakker SJ. Endogenous plasma erythropoietin, cardiovascular mortality and all-cause mortality in renal transplant recipients. Am J Transplant. 2012 Feb;12(2):485-91. doi: 10.1111/j.1600-6143.2011.03825.x. Epub 2011 Nov 4. Erratum In: Am J Transplant. 2012 Mar;12(3):797.</citation>
    <PMID>22054202</PMID>
  </results_reference>
  <results_reference>
    <citation>Deetman PE, Zelle DM, Homan van der Heide JJ, Navis GJ, Gans RO, Bakker SJ. Plasma bilirubin and late graft failure in renal transplant recipients. Transpl Int. 2012 Aug;25(8):876-81. doi: 10.1111/j.1432-2277.2012.01515.x. Epub 2012 Jun 21.</citation>
    <PMID>22716194</PMID>
  </results_reference>
  <results_reference>
    <citation>Zelle DM, Dorland HF, Rosmalen JG, Corpeleijn E, Gans RO, Homan van der Heide JJ, van Son WJ, Navis G, Bakker SJ. Impact of depression on long-term outcome after renal transplantation: a prospective cohort study. Transplantation. 2012 Nov 27;94(10):1033-40. doi: 10.1097/TP.0b013e31826bc3c8.</citation>
    <PMID>23064656</PMID>
  </results_reference>
  <results_reference>
    <citation>Zelle DM, Corpeleijn E, Deinum J, Stolk RP, Gans RO, Navis G, Bakker SJ. Pancreatic beta-cell dysfunction and risk of new-onset diabetes after kidney transplantation. Diabetes Care. 2013 Jul;36(7):1926-32. doi: 10.2337/dc12-1894. Epub 2013 Feb 1.</citation>
    <PMID>23378624</PMID>
  </results_reference>
  <results_reference>
    <citation>Zelle DM, Corpeleijn E, Klaassen G, Schutte E, Navis G, Bakker SJ. Fear of Movement and Low Self-Efficacy Are Important Barriers in Physical Activity after Renal Transplantation. PLoS One. 2016 Feb 4;11(2):e0147609. doi: 10.1371/journal.pone.0147609. eCollection 2016.</citation>
    <PMID>26844883</PMID>
  </results_reference>
  <results_reference>
    <citation>Hellemons ME, Sanders JS, Seelen MA, Gans RO, Muller Kobold AC, van Son WJ, Postmus D, Navis GJ, Bakker SJ. Assessment of Cotinine Reveals a Dose-Dependent Effect of Smoking Exposure on Long-term Outcomes After Renal Transplantation. Transplantation. 2015 Sep;99(9):1926-32. doi: 10.1097/TP.0000000000000636.</citation>
    <PMID>25710609</PMID>
  </results_reference>
  <results_reference>
    <citation>Meijer E, Bakker SJ, de Jong PE, Homan van der Heide JJ, van Son WJ, Struck J, Lems SP, Gansevoort RT. Copeptin, a surrogate marker of vasopressin, is associated with accelerated renal function decline in renal transplant recipients. Transplantation. 2009 Aug 27;88(4):561-7. doi: 10.1097/TP.0b013e3181b11ae4.</citation>
    <PMID>19696640</PMID>
  </results_reference>
  <results_reference>
    <citation>Nauta FL, Bakker SJ, van Oeveren W, Navis G, van der Heide JJ, van Goor H, de Jong PE, Gansevoort RT. Albuminuria, proteinuria, and novel urine biomarkers as predictors of long-term allograft outcomes in kidney transplant recipients. Am J Kidney Dis. 2011 May;57(5):733-43. doi: 10.1053/j.ajkd.2010.12.022. Epub 2011 Apr 1. Erratum In: Am J Kidney Dis. 2011 Sep;58(3):500-1.</citation>
    <PMID>21458900</PMID>
  </results_reference>
  <results_reference>
    <citation>de Vries LV, Minovic I, Franssen CFM, van Faassen M, Sanders JS, Berger SP, Navis G, Kema IP, Bakker SJL. The tryptophan/kynurenine pathway, systemic inflammation, and long-term outcome after kidney transplantation. Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F475-F486. doi: 10.1152/ajprenal.00690.2016. Epub 2017 May 10.</citation>
    <PMID>28490533</PMID>
  </results_reference>
  <results_reference>
    <citation>Keyzer CA, Riphagen IJ, Joosten MM, Navis G, Muller Kobold AC, Kema IP, Bakker SJ, de Borst MH; NIGRAM consortium. Associations of 25(OH) and 1,25(OH)2 vitamin D with long-term outcomes in stable renal transplant recipients. J Clin Endocrinol Metab. 2015 Jan;100(1):81-9. doi: 10.1210/jc.2014-3012.</citation>
    <PMID>25361179</PMID>
  </results_reference>
  <results_reference>
    <citation>Keyzer CA, Vermeer C, Joosten MM, Knapen MH, Drummen NE, Navis G, Bakker SJ, de Borst MH. Vitamin K status and mortality after kidney transplantation: a cohort study. Am J Kidney Dis. 2015 Mar;65(3):474-83. doi: 10.1053/j.ajkd.2014.09.014. Epub 2014 Nov 12.</citation>
    <PMID>25453995</PMID>
  </results_reference>
  <results_reference>
    <citation>Baia LC, Humalda JK, Vervloet MG, Navis G, Bakker SJ, de Borst MH; NIGRAM Consortium. Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation. Clin J Am Soc Nephrol. 2013 Nov;8(11):1968-78. doi: 10.2215/CJN.01880213. Epub 2013 Aug 8.</citation>
    <PMID>23929933</PMID>
  </results_reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 2, 2017</study_first_submitted>
  <study_first_submitted_qc>September 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>September 2, 2017</last_update_submitted>
  <last_update_submitted_qc>September 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Center Groningen</investigator_affiliation>
    <investigator_full_name>Stephan J.L. Bakker</investigator_full_name>
    <investigator_title>Internist-Neprologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Death</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>The data can be shared with other researchers. The researchers will then receive an anonymized dataset. The PI of the study will be co-author on papers that come out of the analyses.</ipd_description>
  </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/NCT03272854
org study id: METc2001/039
nct id: NCT03272854
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Short-term (1-year) results of renal transplantation are now excellent (over 95%). Long-term
      (10-year and longer) results are, however, still disappointing. Where most research has
      focused on immunosuppression and infections, the investigators hypothesize that in renal
      transplant recipient, amongst others overweight, obesity, chronic use of immunosuppressive
      drugs and impaired renal function contribute to insulin resistance and chronic low-grade
      inflammation, which pose the renal transplant recipients at increased risk for cardiovascular
      disease, decline of function of the transplanted kidney and other complications, including
      post-transplant diabetes. This study is a biobank and cohort study which investigates this
      hypothesis.
Short-term (1-year) results of renal transplantation are now excellent (over 95%). Long-term
      (10-year and longer) results are, however, still disappointing. Where most research has
      focused on immunosuppression and infections, the investigators hypothesize that in renal
      transplant recipient, amongst others overweight, obesity, chronic use of immunosuppressive
      drugs and impaired renal function contribute to insulin resistance and chronic low-grade
      inflammation, which pose the renal transplant recipients at increased risk for cardiovascular
      disease, decline of function of the transplanted kidney and other complications, including
      post-transplant diabetes. To investigate this hypothesis we have detailedly phenotyped 606
      renal transplant recipients who at the time of inclusion all were one year or more after
      transplantation, therewith providing a representation of stable outpatient renal trannsplant
      recipients late after renal transplantation. At the time of these baseline measurements, we
      also created a biobank with plasma, serum and aliquots of 24h urine collections. Beyond
      baseline, we have a regular update on adverse events, including all-cause mortality,
      cause-specific mortality, graft failure and development of new-onset diabetes after
      transplantation (NODAT).
observational model: Cohort
time perspective: Prospective
measure: All-Cause Mortality
time frame: 30 years
description: All-Cause Mortality
measure: Graft Failure
time frame: 30 years
description: Death-Censored Graft Failure
measure: New Onset Diabetes After Transplantation
time frame: 30 years
description: NODAT
measure: Cardiovascular Mortality
time frame: 30 years
description: Cause-Specific Mortality
measure: Non-Cardiovascular Mortality
time frame: 30 years
description: Cause-Specific Mortality
measure: Venous Thrombosis
time frame: 30 years
description: Venous Thrombosis
arm group label: Renal Transplant Recipients
description: A cohort or renal transplant recipients, all more than 1 year after transplantation at inclusion
intervention type: Other
intervention name: No intervention performed, the study is observational
arm group label: Renal Transplant Recipients
EDTA plasma, serum, aliquots of 24h urine collections all stored at -80 degrees Centigrade.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stephan JL Bakker, MD, PhD
role: Principal Investigator
affiliation: University Medical Center Groningen
citation: de Vries AP, Bakker SJ, van Son WJ, van der Heide JJ, Ploeg RJ, The HT, de Jong PE, Gans RO. Metabolic syndrome is associated with impaired long-term renal allograft function; not all component criteria contribute equally. Am J Transplant. 2004 Oct;4(10):1675-83. doi: 10.1111/j.1600-6143.2004.00558.x.
PMID: 15367224
citation: van Ree RM, de Vries AP, Oterdoom LH, The TH, Gansevoort RT, Homan van der Heide JJ, van Son WJ, Ploeg RJ, de Jong PE, Gans RO, Bakker SJ. Abdominal obesity and smoking are important determinants of C-reactive protein in renal transplant recipients. Nephrol Dial Transplant. 2005 Nov;20(11):2524-31. doi: 10.1093/ndt/gfi052. Epub 2005 Aug 22.
PMID: 16115856
citation: Oterdoom LH, de Vries AP, van Son WJ, van der Heide JJ, Ploeg RJ, Gansevoort RT, de Jong PE, Gans RO, Bakker SJ. Validation of insulin resistance indexes in a stable renal transplant population. Diabetes Care. 2005 Oct;28(10):2424-9. doi: 10.2337/diacare.28.10.2424.
PMID: 16186274
citation: Hartog JW, de Vries AP, Bakker SJ, Graaff R, van Son WJ, van der Heide JJ, Gans RO, Wolffenbuttel BH, de Jong PE, Smit AJ. Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients. Nephrol Dial Transplant. 2006 Aug;21(8):2263-9. doi: 10.1093/ndt/gfl132. Epub 2006 Apr 5.
PMID: 16597636
citation: van Ree RM, Oterdoom LH, de Vries AP, Gansevoort RT, van der Heide JJ, van Son WJ, Ploeg RJ, de Jong PE, Gans RO, Bakker SJ. Elevated levels of C-reactive protein independently predict accelerated deterioration of graft function in renal transplant recipients. Nephrol Dial Transplant. 2007 Jan;22(1):246-53. doi: 10.1093/ndt/gfl511. Epub 2006 Sep 23.
PMID: 16998222
citation: Oterdoom LH, de Vries AP, Gansevoort RT, van Son WJ, van der Heide JJ, Ploeg RJ, de Jong PE, Gans RO, Bakker SJ. Determinants of insulin resistance in renal transplant recipients. Transplantation. 2007 Jan 15;83(1):29-35. doi: 10.1097/01.tp.0000245844.27683.48.
PMID: 17220787
citation: Oterdoom LH, de Vries AP, Gansevoort RT, de Jong PE, Gans RO, Bakker SJ. Fasting insulin modifies the relation between age and renal function. Nephrol Dial Transplant. 2007 Jun;22(6):1587-92. doi: 10.1093/ndt/gfm037. Epub 2007 Feb 21.
PMID: 17314207
citation: Gross S, van Ree RM, Oterdoom LH, de Vries AP, van Son WJ, de Jong PE, Navis GJ, Zuurman MW, Bierhaus A, Gans RO, Bakker SJ. Low levels of sRAGE are associated with increased risk for mortality in renal transplant recipients. Transplantation. 2007 Sep 15;84(5):659-63. doi: 10.1097/01.tp.0000280556.16275.2a.
PMID: 17876282
citation: van Timmeren MM, Vaidya VS, van Ree RM, Oterdoom LH, de Vries AP, Gans RO, van Goor H, Stegeman CA, Bonventre JV, Bakker SJ. High urinary excretion of kidney injury molecule-1 is an independent predictor of graft loss in renal transplant recipients. Transplantation. 2007 Dec 27;84(12):1625-30. doi: 10.1097/01.tp.0000295982.78039.ef.
PMID: 18165774
citation: Lijfering WM, de Vries AP, Veeger NJ, van Son WJ, Bakker SJ, van der Meer J. Possible contribution of cytomegalovirus infection to the high risk of (recurrent) venous thrombosis after renal transplantation. Thromb Haemost. 2008 Jan;99(1):127-32. doi: 10.1160/TH07-05-0340.
PMID: 18217144
citation: Oterdoom LH, van Ree RM, de Vries AP, Gansevoort RT, Schouten JP, van Son WJ, Homan van der Heide JJ, Navis G, de Jong PE, Gans RO, Bakker SJ. Urinary creatinine excretion reflecting muscle mass is a predictor of mortality and graft loss in renal transplant recipients. Transplantation. 2008 Aug 15;86(3):391-8. doi: 10.1097/TP.0b013e3181788aea.
PMID: 18698241
citation: van Ree RM, Oterdoom LH, de Vries AP, Homan van der Heide JJ, van Son WJ, Navis G, Gans RO, Bakker SJ. Circulating markers of endothelial dysfunction interact with proteinuria in predicting mortality in renal transplant recipients. Transplantation. 2008 Dec 27;86(12):1713-9. doi: 10.1097/TP.0b013e3181903d25.
PMID: 19104410
citation: Hartog JW, Gross S, Oterdoom LH, van Ree RM, de Vries AP, Smit AJ, Schouten JP, Nawroth PP, Gans RO, van Son WJ, Bierhaus A, Bakker SJ. Skin-autofluorescence is an independent predictor of graft loss in renal transplant recipients. Transplantation. 2009 Apr 15;87(7):1069-77. doi: 10.1097/TP.0b013e31819d3173.
PMID: 19352130
citation: Oterdoom LH, de Vries AP, van Ree RM, Gansevoort RT, van Son WJ, van der Heide JJ, Navis G, de Jong PE, Gans RO, Bakker SJ. N-terminal pro-B-type natriuretic peptide and mortality in renal transplant recipients versus the general population. Transplantation. 2009 May 27;87(10):1562-70. doi: 10.1097/TP.0b013e3181a4bb80.
PMID: 19461495
citation: van Ree RM, de Vries AP, Oterdoom LH, Seelen MA, Gansevoort RT, Schouten JP, Struck J, Navis G, Gans RO, van der Heide JJ, van Son WJ, Bakker SJ. Plasma procalcitonin is an independent predictor of graft failure late after renal transplantation. Transplantation. 2009 Jul 27;88(2):279-87. doi: 10.1097/TP.0b013e3181ac9ea0.
PMID: 19623026
citation: van Ree RM, de Vries AP, Zelle DM, de Vries LV, Oterdoom LH, Gans RO, Schouten JP, Lems SP, van Son WJ, Bakker SJ. Latent cytomegalovirus infection is an independent risk factor for late graft failure in renal transplant recipients. Med Sci Monit. 2011 Nov;17(11):CR609-617. doi: 10.12659/msm.882045.
PMID: 22037739
citation: Said MY, Deetman PE, de Vries AP, Zelle DM, Gans RO, Navis G, Joosten MM, Bakker SJ. Causal path analyses of the association of protein intake with risk of mortality and graft failure in renal transplant recipients. Clin Transplant. 2015 May;29(5):447-57. doi: 10.1111/ctr.12536. Epub 2015 Apr 23.
PMID: 25739949
citation: Eisenga MF, Dullaart RP, Berger SP, Sloan JH, de Vries AP, Bakker SJ, Gaillard CA. Association of hepcidin-25 with survival after kidney transplantation. Eur J Clin Invest. 2016 Dec;46(12):994-1001. doi: 10.1111/eci.12682. Epub 2016 Oct 26.
PMID: 27696386
citation: Adepu S, Katta K, Tietge UJ, Kwakernaak AJ, Dam W, van Goor H, Dullaart RP, Navis GJ, Bakker SJ, van den Born J. Hepatic syndecan-1 changes associate with dyslipidemia after renal transplantation. Am J Transplant. 2014 Oct;14(10):2328-38. doi: 10.1111/ajt.12842. Epub 2014 Aug 25.
PMID: 25154787
citation: Annema W, Dikkers A, de Boer JF, Dullaart RP, Sanders JS, Bakker SJ, Tietge UJ. HDL Cholesterol Efflux Predicts Graft Failure in Renal Transplant Recipients. J Am Soc Nephrol. 2016 Feb;27(2):595-603. doi: 10.1681/ASN.2014090857. Epub 2015 Aug 28.
PMID: 26319244
citation: Leberkuhne LJ, Ebtehaj S, Dimova LG, Dikkers A, Dullaart RP, Bakker SJ, Tietge UJ. The predictive value of the antioxidative function of HDL for cardiovascular disease and graft failure in renal transplant recipients. Atherosclerosis. 2016 Jun;249:181-5. doi: 10.1016/j.atherosclerosis.2016.04.008. Epub 2016 Apr 8.
PMID: 27107804
citation: Eisenga MF, Zelle DM, Sloan JH, Gaillard CAJM, Bakker SJL, Dullaart RPF. High Serum PCSK9 Is Associated With Increased Risk of New-Onset Diabetes After Transplantation in Renal Transplant Recipients. Diabetes Care. 2017 Jul;40(7):894-901. doi: 10.2337/dc16-2258. Epub 2017 May 1.
PMID: 28461454
citation: Eisenga MF, Dullaart RPF, Berger SP, Touw DJ, Bakker SJL, Gaillard CAJM. Urinary prednisolone excretion is a determinant of serum hepcidin levels in renal transplant recipients. Am J Hematol. 2017 Aug;92(8):E173-E175. doi: 10.1002/ajh.24785. Epub 2017 Jun 9. No abstract available.
PMID: 28494514
citation: Sotomayor CG, Eisenga MF, Gomes Neto AW, Ozyilmaz A, Gans ROB, Jong WHA, Zelle DM, Berger SP, Gaillard CAJM, Navis GJ, Bakker SJ. Vitamin C Depletion and All-Cause Mortality in Renal Transplant Recipients. Nutrients. 2017 Jun 2;9(6):568. doi: 10.3390/nu9060568.
PMID: 28574431
citation: van Timmeren MM, Lems SP, Hepkema BG, Bakker SJ. Anti-human leukocyte antigen antibodies and development of graft failure after renal transplantation. Transplantation. 2009 Dec 27;88(12):1399-400. doi: 10.1097/TP.0b013e3181bc3ef0. No abstract available.
PMID: 20029338
citation: Zelle DM, Corpeleijn E, van Ree RM, Stolk RP, van der Veer E, Gans RO, Homan van der Heide JJ, Navis G, Bakker SJ. Markers of the hepatic component of the metabolic syndrome as predictors of mortality in renal transplant recipients. Am J Transplant. 2010 Jan;10(1):106-14. doi: 10.1111/j.1600-6143.2009.02876.x. Epub 2009 Nov 24.
PMID: 19951280
citation: van Ree RM, Gross S, Zelle DM, van der Heide JJ, Schouten JP, van Son WJ, Gans RO, Bakker SJ. Influence of C-reactive protein and urinary protein excretion on prediction of graft failure and mortality by serum albumin in renal transplant recipients. Transplantation. 2010 May 27;89(10):1247-54. doi: 10.1097/TP.0b013e3181d720e3.
PMID: 20559032
citation: Zelle DM, Corpeleijn E, Stolk RP, de Greef MH, Gans RO, van der Heide JJ, Navis G, Bakker SJ. Low physical activity and risk of cardiovascular and all-cause mortality in renal transplant recipients. Clin J Am Soc Nephrol. 2011 Apr;6(4):898-905. doi: 10.2215/CJN.03340410. Epub 2011 Mar 3.
PMID: 21372213
citation: Agarwal PK, Hellemons ME, Zelle DM, van Ree RM, van den Born J, van der Heide JJ, Gans RO, van Son WJ, Navis G, Bakker SJ. Smoking is a risk factor for graft failure and mortality after renal transplantation. Am J Nephrol. 2011;34(1):26-31. doi: 10.1159/000328903. Epub 2011 Jun 9.
PMID: 21659736
citation: Zelle DM, Agarwal PK, Ramirez JL, van der Heide JJ, Corpeleijn E, Gans RO, Navis G, Bakker SJ. Alcohol consumption, new onset of diabetes after transplantation, and all-cause mortality in renal transplant recipients. Transplantation. 2011 Jul 27;92(2):203-9. doi: 10.1097/TP.0b013e318222ca10.
PMID: 21685828
citation: Sinkeler SJ, Zelle DM, Homan van der Heide JJ, Gans RO, Navis G, Bakker SJ. Endogenous plasma erythropoietin, cardiovascular mortality and all-cause mortality in renal transplant recipients. Am J Transplant. 2012 Feb;12(2):485-91. doi: 10.1111/j.1600-6143.2011.03825.x. Epub 2011 Nov 4. Erratum In: Am J Transplant. 2012 Mar;12(3):797.
PMID: 22054202
citation: Deetman PE, Zelle DM, Homan van der Heide JJ, Navis GJ, Gans RO, Bakker SJ. Plasma bilirubin and late graft failure in renal transplant recipients. Transpl Int. 2012 Aug;25(8):876-81. doi: 10.1111/j.1432-2277.2012.01515.x. Epub 2012 Jun 21.
PMID: 22716194
citation: Zelle DM, Dorland HF, Rosmalen JG, Corpeleijn E, Gans RO, Homan van der Heide JJ, van Son WJ, Navis G, Bakker SJ. Impact of depression on long-term outcome after renal transplantation: a prospective cohort study. Transplantation. 2012 Nov 27;94(10):1033-40. doi: 10.1097/TP.0b013e31826bc3c8.
PMID: 23064656
citation: Zelle DM, Corpeleijn E, Deinum J, Stolk RP, Gans RO, Navis G, Bakker SJ. Pancreatic beta-cell dysfunction and risk of new-onset diabetes after kidney transplantation. Diabetes Care. 2013 Jul;36(7):1926-32. doi: 10.2337/dc12-1894. Epub 2013 Feb 1.
PMID: 23378624
citation: Zelle DM, Corpeleijn E, Klaassen G, Schutte E, Navis G, Bakker SJ. Fear of Movement and Low Self-Efficacy Are Important Barriers in Physical Activity after Renal Transplantation. PLoS One. 2016 Feb 4;11(2):e0147609. doi: 10.1371/journal.pone.0147609. eCollection 2016.
PMID: 26844883
citation: Hellemons ME, Sanders JS, Seelen MA, Gans RO, Muller Kobold AC, van Son WJ, Postmus D, Navis GJ, Bakker SJ. Assessment of Cotinine Reveals a Dose-Dependent Effect of Smoking Exposure on Long-term Outcomes After Renal Transplantation. Transplantation. 2015 Sep;99(9):1926-32. doi: 10.1097/TP.0000000000000636.
PMID: 25710609
citation: Meijer E, Bakker SJ, de Jong PE, Homan van der Heide JJ, van Son WJ, Struck J, Lems SP, Gansevoort RT. Copeptin, a surrogate marker of vasopressin, is associated with accelerated renal function decline in renal transplant recipients. Transplantation. 2009 Aug 27;88(4):561-7. doi: 10.1097/TP.0b013e3181b11ae4.
PMID: 19696640
citation: Nauta FL, Bakker SJ, van Oeveren W, Navis G, van der Heide JJ, van Goor H, de Jong PE, Gansevoort RT. Albuminuria, proteinuria, and novel urine biomarkers as predictors of long-term allograft outcomes in kidney transplant recipients. Am J Kidney Dis. 2011 May;57(5):733-43. doi: 10.1053/j.ajkd.2010.12.022. Epub 2011 Apr 1. Erratum In: Am J Kidney Dis. 2011 Sep;58(3):500-1.
PMID: 21458900
citation: de Vries LV, Minovic I, Franssen CFM, van Faassen M, Sanders JS, Berger SP, Navis G, Kema IP, Bakker SJL. The tryptophan/kynurenine pathway, systemic inflammation, and long-term outcome after kidney transplantation. Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F475-F486. doi: 10.1152/ajprenal.00690.2016. Epub 2017 May 10.
PMID: 28490533
citation: Keyzer CA, Riphagen IJ, Joosten MM, Navis G, Muller Kobold AC, Kema IP, Bakker SJ, de Borst MH; NIGRAM consortium. Associations of 25(OH) and 1,25(OH)2 vitamin D with long-term outcomes in stable renal transplant recipients. J Clin Endocrinol Metab. 2015 Jan;100(1):81-9. doi: 10.1210/jc.2014-3012.
PMID: 25361179
citation: Keyzer CA, Vermeer C, Joosten MM, Knapen MH, Drummen NE, Navis G, Bakker SJ, de Borst MH. Vitamin K status and mortality after kidney transplantation: a cohort study. Am J Kidney Dis. 2015 Mar;65(3):474-83. doi: 10.1053/j.ajkd.2014.09.014. Epub 2014 Nov 12.
PMID: 25453995
citation: Baia LC, Humalda JK, Vervloet MG, Navis G, Bakker SJ, de Borst MH; NIGRAM Consortium. Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation. Clin J Am Soc Nephrol. 2013 Nov;8(11):1968-78. doi: 10.2215/CJN.01880213. Epub 2013 Aug 8.
PMID: 23929933
responsible party type: Principal Investigator
investigator affiliation: University Medical Center Groningen
investigator full name: Stephan J.L. Bakker
investigator title: Internist-Neprologist
mesh term: Insulin Resistance
mesh term: Inflammation
mesh term: Death
sharing ipd: Undecided
ipd description: The data can be shared with other researchers. The researchers will then receive an anonymized dataset. The PI of the study will be co-author on papers that come out of the analyses.