Pro-neurotensin depends on renal function and is related to all-cause mortality in chronic kidney disease.
Eur J Endocrinol
; 183(3): 233-244, 2020 Sep.
Article
em En
| MEDLINE
| ID: mdl-32508317
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neurotensina
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Insuficiência Renal Crônica
Tipo de estudo:
Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Endocrinol
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha