Research Article: The shift from high to low turnover bone disease after parathyroidectomy is associated with the progression of vascular calcification in hemodialysis patients: A 12-month follow-up study

Date Published: April 6, 2017

Publisher: Public Library of Science

Author(s): Fabiana Rodrigues Hernandes, Maria Eugênia Fernandes Canziani, Fellype Carvalho Barreto, Rodrigo Oliveira Santos, Valéria de Melo Moreira, Carlos Eduardo Rochitte, Aluizio Barbosa Carvalho, Jeff M. Sands.

http://doi.org/10.1371/journal.pone.0174811

Abstract

Parathyroidectomy (PTX) may cause low levels of PTH, leading to an excessive reduction of bone turnover, which is associated with poor outcomes in dialysis patients, including vascular calcification (VC). We aimed to prospectively investigate the impact of PTX on bone remodeling and its potential consequence on the progression of VC in hemodialysis patients. In this prospective study, 19 hemodialysis patients with severe secondary hyperparathyroidism (sHPT) were evaluated. All patients underwent laboratorial tests and coronary tomography at baseline and, 6 and 12 months after PTX; bone biopsy was performed at baseline and 12-month. At baseline, all patients had increased PTH levels up to 2500 pg/mL and high turnover bone disease in their bone biopsies. Fourteen (74%) patients had VC. During the follow-up, there was a significant decrease of PTH at 6 and 12-month. At 12-month, 90% of the patients evolved to low turnover bone disease. During the period of the hungry bone syndrome (first 6 months), no change of coronary calcium score was observed. However, calcium score increased significantly thereafter (12th month). There was an association between VC progression and the severity of low turnover bone disease. In conclusion, the shift from high to low turnover bone disease after PTX occurs in parallel to VC progression, contributing to the understanding of the complex pathophysiology involving mineral metabolism and cardiovascular disease in hemodialysis patients.

Partial Text

Secondary hyperparathyroidism (sHPT) is a frequent and severe co-morbidity among chronic kidney disease (CKD) patients, which is associated with cardiovascular disease, the main cause of the high rate of mortality in this population [1–6]. Although the current pharmacological treatment has changed the course of sHPT, severe forms of the disease still require invasive procedures, such as parathyroidectomy (PTX) [7]. In the setting of severe sHPT, PTX has been considered to provide clinical short term benefits. However, the post-PTX resultant low levels of PTH may lead to an excessive reduction of bone turnover, which is associated with poor outcomes in dialysis patients. In fact, it has been demonstrated, in cross-sectional studies, that low turnover bone disease is related to vascular calcification (VC) in both non-dialyzed and dialyzed CKD patients [8–9]. It is well known that VC is a frequent and severe comorbidity in CKD patients [10–14]. Of note, not only the presence of VC, but also its progression has been associated with high mortality rate [15–16]. Thus, we aimed to prospectively investigate the impact of PTX on bone remodeling and its potential consequence on the progression of VC in hemodialysis patients.

Hemodialysis patients referred to PTX due to severe sHPT were approached to participate in this study. Exclusion criteria were age below 18 or above 65 years, presence of positive deferroxamine test, serious gastrointestinal disease, ethanol or drug abuse, active malignancy, human immunodeficiency virus infection, chronic inflammatory disease, previous myocardial revascularization, uncontrolled diabetes mellitus or hypertension, body weight greater than 100 kg, pregnancy or breast-feeding, and use of corticosteroids, antiarrhythmic or seizure drugs. Nineteen out of 25 screened patients completed a 12-month follow-up. The reasons of drop-out were: death (2 patients), persistent sHPT (2 patients), withdraw (1 patient) and lung tuberculosis (1 patient). These patients were not different regarding baseline demographic, laboratory, coronary tomography or bone biopsy characteristics from those who completed the study.

Demographic, laboratory, bone biopsy and coronary tomography parameters at baseline, 6 and 12-month from the 19 patients who completed the study are shown in Table 1. Patients were relatively young, white women, long time on dialysis and 63% with BMI < 23 kg/m2. Most of the patients had hypertension (68%) and none had diabetes as comorbid condition. Six patients were not submitted to autotransplantation after PTX due to the absence of suitable parathyroid tissue. In the current study, we could observe that the shift from high to low turnover bone disease after PTX was related to the progression of VC in hemodialysis patients.   Source: http://doi.org/10.1371/journal.pone.0174811

 

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