IMR Press / RCM / Volume 23 / Issue 9 / DOI: 10.31083/j.rcm2309311
Open Access Original Research
Decreased Cathepsin-K Mirrors the Severity of Subclinical Atherosclerosis in Kidney Transplant Recipients
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1 Renal Unit, “Magna Graecia'' University, 88100 Catanzaro, Italy
2 Clinical Pathology Lab, “Magna Graecia'' University, 88100 Catanzaro, Italy
3 Pharmacology Unit, “Magna Graecia” University, 88100 Catanzaro, Italy
*Correspondence: davide.bolignano@gmail.com (Davide Bolignano)
Academic Editor: Brian Tomlinson
Rev. Cardiovasc. Med. 2022, 23(9), 311; https://doi.org/10.31083/j.rcm2309311
Submitted: 1 July 2022 | Revised: 2 August 2022 | Accepted: 8 August 2022 | Published: 13 September 2022
(This article belongs to the Section CardioRenal)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

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
Figures
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