Pro-neurotensin depends on renal function and is related to all-cause mortality in chronic kidney disease
| Autor: | Peter Kovacs, Joachim Beige, Matthias Anders, Matthias Blüher, Mathias Fasshauer, Anke Tönjes, Markus Scholz, Ronny Baber, Dorit Schleinitz, Markus Löffler, Nora Klöting, Sabine Paeschke, Annett Hoffmann, Ingolf Bast, Cornelia Enzenbach, Abdul Rashid Qureshi, Peter Stenvinkel, Michael Stumvoll, Marcin Nowicki, Raymond C. Harris, Thomas Ebert, Anette Bachmann, Ming-Zhi Zhang, Susan Kralisch, Jürgen Kratzsch, Kerstin Wirkner |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty Cross-sectional study Endocrinology Diabetes and Metabolism Urinary system Renal function 030209 endocrinology & metabolism Kidney Gastroenterology Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Meta-Analysis as Topic Internal medicine Animals Humans Medicine Longitudinal Studies Renal Insufficiency Chronic Neurotensin Aged Aged 80 and over business.industry Hazard ratio Kidney metabolism General Medicine Middle Aged medicine.disease Cross-Sectional Studies 030220 oncology & carcinogenesis Cohort Population study Female business Glomerular Filtration Rate Kidney disease |
| Zdroj: | Eur. J. Endocrinol. 183, 233-244 (2020) |
| ISSN: | 1479-683X 0804-4643 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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