Increased circulating Cathepsin-K levels reflect PTH control in chronic hemodialysis patients

Bolignano, Davide; Greco, Marta; Arcidiacono, Valentina; Tripolino, Omar; Vita, Caterina; Provenzano, Michele; Donato, Cinzia; Chiarella, Salvatore; Fuiano, Giorgio; Sarro, Giovambattista De; Russo, Emilio; Andreucci, Michele; Foti, Daniela; Coppolino, Giuseppe

doi:10.1007/s40620-020-00801-5

Cited by 4 publications

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References 27 publications

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“…No less important, such levels were almost comparable to those measured in healthy controls. Hence, Ktx seems to normalize the altered balance in CatK which characterizes HD patients [ 13 , 14 ]. As previously observed, increased CatK in HD patients are largely influenced by the severity of bone mineral alterations and inflammation [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Hence, Ktx seems to normalize the altered balance in CatK which characterizes HD patients [ 13 , 14 ]. As previously observed, increased CatK in HD patients are largely influenced by the severity of bone mineral alterations and inflammation [ 14 ]. Ktx is known to ameliorate most of the complications related to advanced CKD.…”

Section: Discussionmentioning

confidence: 99%

“…Conclusions: In Ktx recipients, reduced CatK levels reflect the time-dependent improvement in the uremic milieu, cardiac adaptations and, above all, the severity of subclinical atherosclerosis. CatK measurement in Ktx may therefore hold significance for improving early CV risk stratification.Keywords: kidney transplantation; Cathepsin-K; carotid intima-media thickness; subclinical atherosclerosis Recently, we reported increased CatK levels among chronic HD patients which reflected an altered bone mineral metabolism, also holding prognostic value for CV mortality [13,14]. To the best of our knowledge, however, no study has analysed so far such protease in the context of Ktx, particularly in relationship with the presence of early, asymptomatic CV disease.…”

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confidence: 99%

“…Keywords: kidney transplantation; Cathepsin-K; carotid intima-media thickness; subclinical atherosclerosis Recently, we reported increased CatK levels among chronic HD patients which reflected an altered bone mineral metabolism, also holding prognostic value for CV mortality [13,14]. To the best of our knowledge, however, no study has analysed so far such protease in the context of Ktx, particularly in relationship with the presence of early, asymptomatic CV disease.…”

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confidence: 99%

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Decreased Cathepsin-K Mirrors the Severity of Subclinical Atherosclerosis in Kidney Transplant Recipients

Bolignano¹,

Greco²,

Arcidiacono³

et al. 2022

Rev. Cardiovasc. Med.

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Background: In kidney transplantation (Ktx) recipients, cardiovascular (CV) disease remains the leading cause of death. Abnormal carotid intima-media thickness (IMT) represents a valid indicator of incipient atherosclerosis also in this setting. Cathepsin-K (CatK) is a cysteine protease involved in vascular remodelling, as well as in progressive atherosclerosis. In this study we evaluated clinical predictors of CatK in Ktx recipients, with a particular focus on its possible relationships with subclinical atherosclerosis. Methods: Circulating CatK was measured in 40 stable Ktx recipients together with several laboratory, clinical and echocardiography parameters. 30 healthy subjects and 30 hemodialysis (HD) patients served as controls for CatK values. Carotid IMT was measured in Ktx and these subjects were then categorized according to age-gender reference cut-offs of normal IMT. Results: CatK levels were similar in Ktx recipients and healthy subjects but significantly reduced as compared to HD (p = 0.0001). In Ktx, at multivariate analyses CatK was associated with the LV end-diastolic volume (LVEDVi) (β = 0.514; p = 0.05), Ktx vintage (β = -0.333; p = 0.05) and mean IMT (β = -0.545; p = 0.05); this latter robust inverse association was confirmed also in another multivariate model with IMT as the dependent variable. Logistic regression analyses confirmed the beneficial meaning of CatK increase towards subclinical atherosclerosis [Odds Ratio (OR) 0.761; 95% Confidence Interval (CI) 0.569-0.918, p = 0.04]. At Receiver Operating Characteristics (ROC) analyses, CatK held a remarkable discriminatory power in identifying Ktx patients with abnormally increased IMT [Area Under the Curve (AUC) 0.763; 95% CI 0.601-0.926; p = 0.001]). Conclusions: In Ktx recipients, reduced CatK levels reflect the time-dependent improvement in the uremic milieu, cardiac adaptations and, above all, the severity of subclinical atherosclerosis. CatK measurement in Ktx may therefore hold significance for improving early CV risk stratification.Keywords: kidney transplantation; Cathepsin-K; carotid intima-media thickness; subclinical atherosclerosis Recently, we reported increased CatK levels among chronic HD patients which reflected an altered bone mineral metabolism, also holding prognostic value for CV mortality [13,14]. To the best of our knowledge, however, no study has analysed so far such protease in the context of Ktx, particularly in relationship with the presence of early, asymptomatic CV disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Decreased Cathepsin-K Mirrors the Severity of Subclinical Atherosclerosis in Kidney Transplant Recipients

Bolignano¹,

Greco²,

Arcidiacono³

et al. 2022

Rev. Cardiovasc. Med.

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Role of Vitamin K in Chronic Kidney Disease: A Focus on Bone and Cardiovascular Health

Bellone

Cinquegrani

Nicotera³

et al. 2022

IJMS

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Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic disturbances, bone tissue and metabolism alterations, and vascular calcification (VC) exists and has been defined as chronic kidney disease–mineral and bone disorder (CKD-MBD). Poor vitamin K status seems to have a key role in the progression of CKD, but also in the onset and advance of both bone and cardiovascular complications. Three forms of vitamin K are currently known: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC. This review focuses on the biochemical and functional characteristics of vitamin K vitamers, suggesting this nutrient as a possible marker of kidney, CV, and bone damage in the CKD population and exploring its potential use for promoting health in this clinical setting. Treatment strategies for CKD-associated osteoporosis and CV disease should include vitamin K supplementation. However, further randomized clinical studies are needed to assess the safety and the adequate dosage to prevent these CKD complications.

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Cathepsin K in Pathological Conditions and New Therapeutic and Diagnostic Perspectives

Mijanović

Jakovleva²,

Branković

et al. 2022

IJMS

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Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in bone resorption. Changes in levels of CatK are associated with various pathological conditions, primarily related to bone and cartilage degradation, such as pycnodysostosis (associated with CatK deficiency), osteoporosis, and osteoarthritis (associated with CatK overexpression). Recently, the increased secretion of CatK is being highly correlated to vascular inflammation, hypersensitivity pneumonitis, Wegener granulomatosis, berylliosis, tuberculosis, as well as with tumor progression. Due to the wide spectrum of diseases in which CatK is involved, the design and validation of active site-specific inhibitors has been a subject of keen interest in pharmaceutical companies in recent decades. In this review, we summarized the molecular background of CatK and its involvement in various diseases, as well as its clinical significance for diagnosis and therapy.

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Increased circulating Cathepsin-K levels reflect PTH control in chronic hemodialysis patients

Cited by 4 publications

References 27 publications

Decreased Cathepsin-K Mirrors the Severity of Subclinical Atherosclerosis in Kidney Transplant Recipients

Decreased Cathepsin-K Mirrors the Severity of Subclinical Atherosclerosis in Kidney Transplant Recipients

Role of Vitamin K in Chronic Kidney Disease: A Focus on Bone and Cardiovascular Health

Cathepsin K in Pathological Conditions and New Therapeutic and Diagnostic Perspectives

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