Cargando…

Cortisol excess in chronic kidney disease – A review of changes and impact on mortality

Chronic kidney disease (CKD) describes the long-term condition of impaired kidney function from any cause. CKD is common and associated with a wide array of complications including higher mortality, cardiovascular disease, hypertension, insulin resistance, dyslipidemia, sarcopenia, osteoporosis, abe...

Descripción completa

Detalles Bibliográficos
Autores principales: Sagmeister, Michael S., Harper, Lorraine, Hardy, Rowan S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886668/
https://www.ncbi.nlm.nih.gov/pubmed/36733794
http://dx.doi.org/10.3389/fendo.2022.1075809
_version_ 1784880180892794880
author Sagmeister, Michael S.
Harper, Lorraine
Hardy, Rowan S.
author_facet Sagmeister, Michael S.
Harper, Lorraine
Hardy, Rowan S.
author_sort Sagmeister, Michael S.
collection PubMed
description Chronic kidney disease (CKD) describes the long-term condition of impaired kidney function from any cause. CKD is common and associated with a wide array of complications including higher mortality, cardiovascular disease, hypertension, insulin resistance, dyslipidemia, sarcopenia, osteoporosis, aberrant immune function, cognitive impairment, mood disturbances and poor sleep quality. Glucocorticoids are endogenous pleiotropic steroid hormones and their excess produces a pattern of morbidity that possesses considerable overlap with CKD. Circulating levels of cortisol, the major active glucocorticoid in humans, are determined by a complex interplay between several processes. The hypothalamic-pituitary-adrenal axis (HPA) regulates cortisol synthesis and release, 11β-hydroxysteroid dehydrogenase enzymes mediate metabolic interconversion between active and inactive forms, and clearance from the circulation depends on irreversible metabolic inactivation in the liver followed by urinary excretion. Chronic stress, inflammatory states and other aspects of CKD can disturb these processes, enhancing cortisol secretion via the HPA axis and inducing tissue-resident amplification of glucocorticoid signals. Progressive renal impairment can further impact on cortisol metabolism and urinary clearance of cortisol metabolites. Consequently, significant interest exists to precisely understand the dysregulation of cortisol in CKD and its significance for adverse clinical outcomes. In this review, we summarize the latest literature on alterations in endogenous glucocorticoid regulation in adults with CKD and evaluate the available evidence on cortisol as a mechanistic driver of excess mortality and morbidity. The emerging picture is one of subclinical hypercortisolism with blunted diurnal decline of cortisol levels, impaired negative feedback regulation and reduced cortisol clearance. An association between cortisol and adjusted all-cause mortality has been reported in observational studies for patients with end-stage renal failure, but further research is required to assess links between cortisol and clinical outcomes in CKD. We propose recommendations for future research, including therapeutic strategies that aim to reduce complications of CKD by correcting or reversing dysregulation of cortisol.
format Online
Article
Text
id pubmed-9886668
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-98866682023-02-01 Cortisol excess in chronic kidney disease – A review of changes and impact on mortality Sagmeister, Michael S. Harper, Lorraine Hardy, Rowan S. Front Endocrinol (Lausanne) Endocrinology Chronic kidney disease (CKD) describes the long-term condition of impaired kidney function from any cause. CKD is common and associated with a wide array of complications including higher mortality, cardiovascular disease, hypertension, insulin resistance, dyslipidemia, sarcopenia, osteoporosis, aberrant immune function, cognitive impairment, mood disturbances and poor sleep quality. Glucocorticoids are endogenous pleiotropic steroid hormones and their excess produces a pattern of morbidity that possesses considerable overlap with CKD. Circulating levels of cortisol, the major active glucocorticoid in humans, are determined by a complex interplay between several processes. The hypothalamic-pituitary-adrenal axis (HPA) regulates cortisol synthesis and release, 11β-hydroxysteroid dehydrogenase enzymes mediate metabolic interconversion between active and inactive forms, and clearance from the circulation depends on irreversible metabolic inactivation in the liver followed by urinary excretion. Chronic stress, inflammatory states and other aspects of CKD can disturb these processes, enhancing cortisol secretion via the HPA axis and inducing tissue-resident amplification of glucocorticoid signals. Progressive renal impairment can further impact on cortisol metabolism and urinary clearance of cortisol metabolites. Consequently, significant interest exists to precisely understand the dysregulation of cortisol in CKD and its significance for adverse clinical outcomes. In this review, we summarize the latest literature on alterations in endogenous glucocorticoid regulation in adults with CKD and evaluate the available evidence on cortisol as a mechanistic driver of excess mortality and morbidity. The emerging picture is one of subclinical hypercortisolism with blunted diurnal decline of cortisol levels, impaired negative feedback regulation and reduced cortisol clearance. An association between cortisol and adjusted all-cause mortality has been reported in observational studies for patients with end-stage renal failure, but further research is required to assess links between cortisol and clinical outcomes in CKD. We propose recommendations for future research, including therapeutic strategies that aim to reduce complications of CKD by correcting or reversing dysregulation of cortisol. Frontiers Media S.A. 2023-01-17 /pmc/articles/PMC9886668/ /pubmed/36733794 http://dx.doi.org/10.3389/fendo.2022.1075809 Text en Copyright © 2023 Sagmeister, Harper and Hardy https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Sagmeister, Michael S.
Harper, Lorraine
Hardy, Rowan S.
Cortisol excess in chronic kidney disease – A review of changes and impact on mortality
title Cortisol excess in chronic kidney disease – A review of changes and impact on mortality
title_full Cortisol excess in chronic kidney disease – A review of changes and impact on mortality
title_fullStr Cortisol excess in chronic kidney disease – A review of changes and impact on mortality
title_full_unstemmed Cortisol excess in chronic kidney disease – A review of changes and impact on mortality
title_short Cortisol excess in chronic kidney disease – A review of changes and impact on mortality
title_sort cortisol excess in chronic kidney disease – a review of changes and impact on mortality
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886668/
https://www.ncbi.nlm.nih.gov/pubmed/36733794
http://dx.doi.org/10.3389/fendo.2022.1075809
work_keys_str_mv AT sagmeistermichaels cortisolexcessinchronickidneydiseaseareviewofchangesandimpactonmortality
AT harperlorraine cortisolexcessinchronickidneydiseaseareviewofchangesandimpactonmortality
AT hardyrowans cortisolexcessinchronickidneydiseaseareviewofchangesandimpactonmortality