Treatment Failure of Active Vitamin D Therapy in Chronic Kidney Disease: Predictive Factors

Cozzolino, Mario; Covic, Adrian; Martinez-Placencia, Blanca M; Xynos, Konstantinos

doi:10.1159/000441095

Cited by 5 publications

(4 citation statements)

References 52 publications

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“…In patients with CKD, renal 1,25(OH) 2 D synthesis declines as kidney function deteriorates. As a consequence, hypocalcemia and sHPT develop [ 42 ]. Therefore, active vitamin D analogs are administered routinely with the aim to normalize PTH levels.…”

Section: The Parathyroid-kidney Axis In the Regulation Of Vitamin D M...mentioning

confidence: 99%

Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System

Latic

Erben

2022

Nutrients

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The seminal discoveries that parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are major endocrine regulators of vitamin D metabolism led to a significant improvement in our understanding of the pivotal roles of peptide hormones and small proteohormones in the crosstalk between different organs, regulating vitamin D metabolism. The interaction of vitamin D, FGF23 and PTH in the kidney is essential for maintaining mineral homeostasis. The proteohormone FGF23 is mainly secreted from osteoblasts and osteoclasts in the bone. FGF23 acts on proximal renal tubules to decrease production of the active form of vitamin D (1,25(OH)2D) by downregulating transcription of 1α-hydroxylase (CYP27B1), and by activating transcription of the key enzyme responsible for vitamin D degradation, 24-hydroxylase (CYP24A1). Conversely, the peptide hormone PTH stimulates 1,25(OH)2D renal production by upregulating the expression of 1α-hydroxylase and downregulating that of 24-hydroxylase. The circulating concentration of 1,25(OH)2D is a positive regulator of FGF23 secretion in the bone, and a negative regulator of PTH secretion from the parathyroid gland, forming feedback loops between kidney and bone, and between kidney and parathyroid gland, respectively. In recent years, it has become clear that vitamin D signaling has important functions beyond mineral metabolism. Observation of seasonal variations in blood pressure and the subsequent identification of vitamin D receptor (VDR) and 1α-hydroxylase in non-renal tissues such as cardiomyocytes, endothelial and smooth muscle cells, suggested that vitamin D may play a role in maintaining cardiovascular health. Indeed, observational studies in humans have found an association between vitamin D deficiency and hypertension, left ventricular hypertrophy and heart failure, and experimental studies provided strong evidence for a role of vitamin D signaling in the regulation of cardiovascular function. One of the proposed mechanisms of action of vitamin D is that it functions as a negative regulator of the renin-angiotensin-aldosterone system (RAAS). This finding established a novel link between vitamin D and RAAS that was unexplored until then. During recent years, major progress has been made towards a more complete understanding of the mechanisms by which FGF23, PTH, and RAAS regulate vitamin D metabolism, especially at the genomic level. However, there are still major gaps in our knowledge that need to be filled by future research. The purpose of this review is to highlight our current understanding of the molecular mechanisms underlying the interaction between vitamin D, FGF23, PTH, and RAAS, and to discuss the role of these mechanisms in physiology and pathophysiology.

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Section: The Parathyroid-kidney Axis In the Regulation Of Vitamin D M...mentioning

confidence: 99%

Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System

Latic

Erben

2022

Nutrients

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“…The combination of this assay [55] with real assays describing the bioactivity of PTH and also other factors/hormones involved in the pathogenesis of CKD-MBD will be a useful clinical tool to improve patient's outcome in the future. It might be necessary to reevaluate clinical studies in patients with SHPT where iPTH was used as key inclusion criteria or readout [13,[56][57][58][59] .…”

Section: Met8mentioning

confidence: 99%

Why Current PTH Assays Mislead Clinical Decision Making in Patients with Secondary Hyperparathyroidism

Hocher¹,

Yin

2017

Nephron

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Preclinical studies in cell culture systems as well as in whole animal chronic kidney disease (CKD) models showed that parathyroid hormone (PTH), oxidized at the 2 methionine residues (positions 8 and 18), caused a loss of function. This was so far not considered in the development of PTH assays used in current clinical practice. Patients with advanced CKD are subject to oxidative stress, and plasma proteins (including PTH) are targets for oxidants. In patients with CKD, a considerable but variable fraction (about 70 to 90%) of measured PTH appears to be oxidized. Oxidized PTH (oxPTH) does not interact with the PTH receptor resulting in loss of biological activity. Currently used intact PTH (iPTH) assays detect both oxidized and non-oxPTH (n-oxPTH). Clinical studies demonstrated that bioactive, n-oxPTH, but not iPTH nor oxPTH, is associated with mortality in CKD patients.

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“…Apesar dos mecanismos ainda não terem sido plenamente elucidados, sugere-se a associação entre a prevalência da deficiência de vitamina D nas pessoas com DRC e aumento dos riscos de mortalidade por causa cardiovascular, ou seja, é sugerida uma relação entre baixos níveis séricos de vitamina D e o aumento da mortalidade cardiovascular nessa população (7) .…”

Section: Introductionunclassified

Deficiência de vitamina D e mortalidade cardiovascular na doença renal crônica: revisão integrativa

et al. 2021

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Objetivo: analisar os estudos científicos desenvolvidos sobre a deficiência de vitamina D e a mortalidade por causa cardiovascular nas pessoas com doença renal crônica. Método: Trata-se de uma revisão integrativa da literatura a partir das bases de dados LILACS, PubMed, Medline e na biblioteca eletrônica SciELO, utilizando os descritores deficiência de vitamina D, mortalidade cardiovascular e doença renal crônica, sendo selecionados 14 artigos para análise. Resultados: A partir da análise dos artigos selecionados, foi possível identificar que a deficiência de vitamina D e a mortalidade cardiovascular são condições muito frequentes em renais crônicos e, por isso, discutem-se hipóteses de que a correção desta deficiência pode exercer efeitos benéficos sobre a doença e mortalidade cardiovascular nessa população. Conclusão: Há uma intrínseca relação entre a carência de vitamina D e a mortalidade cardiovascular. Entretanto, ainda é discutível se a suplementação de vitamina D reduz a mortalidade cardiovascular nos doentes renais crônicos. Tal hipótese precisa ser testada em ensaios clínicos, ensejando a necessidade de se desenvolver mais pesquisas sobre o tema.

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Treatment Failure of Active Vitamin D Therapy in Chronic Kidney Disease: Predictive Factors

Cited by 5 publications

References 52 publications

Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System

Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System

Why Current PTH Assays Mislead Clinical Decision Making in Patients with Secondary Hyperparathyroidism

Deficiência de vitamina D e mortalidade cardiovascular na doença renal crônica: revisão integrativa

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