Pro-neurotensin depends on renal function and is related to all-cause mortality in chronic kidney disease

in European Journal of Endocrinology
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  • 1 Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
  • 2 Leipzig University Medical Center, IFB AdiposityDiseases, Leipzig, Germany
  • 3 Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
  • 4 Institute of Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
  • 5 Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany
  • 6 nstitute of Anatomy, University of Leipzig, Leipzig, Germany
  • 7 LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany
  • 8 Division of Nephrology and KfH Renal Unit, Hospital St. Georg, Leipzig, Germany
  • 9 Martin-Luther-University Halle/Wittenberg, Halle, Germany
  • 10 Outpatient Nephrology Care Unit, Leipzig, Germany
  • 11 Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Leipzig, Germany
  • 12 Department of Medicine, Division of Nephrology, Vanderbilt University School of Medicine, C3121 MCN, Nashville, Tennessee, USA
  • 13 Department of Medicine, Vanderbilt University School of Medicine, Nashville Veterans Affairs Hospital, Nashville, Tennessee, USA
  • 14 Institute of Nutritional Science, Justus-Liebig-University, Giessen, Germany

Correspondence should be addressed to T Ebert; Email: thomas.ebert@ki.se
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Background:

Patients with chronic kidney disease (CKD) have a high risk of premature cardiovascular diseases (CVD) and show increased mortality. Pro-neurotensin (Pro-NT) was associated with metabolic diseases and predicted incident CVD and mortality. However, Pro-NT regulation in CKD and its potential role linking CKD and mortality have not been investigated, so far.

Methods:

In a central lab, circulating Pro-NT was quantified in three independent cohorts comprising 4715 participants (cohort 1: patients with CKD; cohort 2: general population study; and cohort 3: non-diabetic population study). Urinary Pro-NT was assessed in part of the patients from cohort 1. In a 4th independent cohort, serum Pro-NT was further related to mortality in patients with advanced CKD. Tissue-specific Nts expression was further investigated in two mouse models of diabetic CKD and compared to non-diabetic control mice.

Results:

Pro-NT significantly increased with deteriorating renal function (P < 0.001). In meta-analysis of cohorts 1–3, Pro-NT was significantly and independently associated with estimated glomerular filtration rate (P ≤ 0.002). Patients in the middle/high Pro-NT tertiles at baseline had a higher all-cause mortality compared to the low Pro-NT tertile (Hazard ratio: 2.11, P = 0.046). Mice with severe diabetic CKD did not show increased Nts mRNA expression in different tissues compared to control animals.

Conclusions:

Circulating Pro-NT is associated with impaired renal function in independent cohorts comprising 4715 subjects and is related to all-cause mortality in patients with end-stage kidney disease. Our human and rodent data are in accordance with the hypotheses that Pro-NT is eliminated by the kidneys and could potentially contribute to increased mortality observed in patients with CKD.

Supplementary Materials

    • Supplementary Methods Animal experiments
    • Supplementary Figure 1 Urinary Pro-NT regulation in a subcohort of the cohort 1 (patients with chronic kidney disease)

 

     European Society of Endocrinology

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