Vitamin D receptor (VDR) gene polymorphism is associated with left ventricular (LV) mass and predicts left ventricular hypertrophy (LVH) progression in end-stage renal disease (ESRD) patients

Testa, Alessandra; Mallamaci, Francesca; Benedetto, Francesco; Pisano, Anna; Tripepi, Giovanni; Malatino, Lorenzo; Thadhani, Ravi; Zoccali, Carmine

doi:10.1359/jbmr.090717

Cited by 59 publications

(60 citation statements)

References 27 publications

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“…Although mild-to-moderate degrees of LVH remain powerful independent predictors of survival, the causal relationship of hypertension alone to LVH in CKD remains uncertain. In fact, the data suggest other factors, including altered vitamin D metabolism, may contribute to this alteration [22,26,28,43]. PRIMO will directly test this hypothesis in humans.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Activation and Left Ventricular Hypertrophy in Advanced Kidney Disease

Thadhani

Appelbaum²,

Chang

et al. 2011

Am J Nephrol

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Background: In chronic kidney disease (CKD), left ventricular hypertrophy (LVH) is prevalent and is associated with increased cardiovascular morbidity and mortality. Vitamin D receptor (VDR) activation attenuates LVH progression in animal models. Methods: PRIMO is a multinational, randomized, double-blinded trial with oral paricalcitol in subjects with stages 3–4 CKD, mild-to-moderate LVH and an LV ejection fraction >50%. The primary endpoint is change in the left ventricular mass index (LVMI) compared with placebo after 48 weeks of treatment. The main secondary endpoints are changes in diastolic function parameters. In this paper, we report baseline characteristics from this study. Results: LVMI was 33.0 ± 7.5 g/m^2.7 for males and 30.8 ± 7.2 g/m^2.7 for females (p = 0.04). LVMI correlated with systolic blood pressure (r = 0.24), urine albumin creatinine ratio (r = 0.39), troponin T (r = 0.29), high-sensitivity C-reactive protein (r = 0.25) and plasma levels of B-type brain natriuretic peptide (r = 0.22); all p < 0.01. In multiple linear regression, each remained independently associated with LVMI. The early diastolic velocity of the lateral mitral annulus (E’) was 8.1 ± 2.4 cm/s. E’ was inversely correlated with age in univariate (r = –0.14, p = 0.04) and multivariable (p = 0.02) analysis. Conclusion: Among 227 multinational subjects with stages 3–4 CKD, baseline LVMI correlates with baseline blood pressure, urine albumin creatinine ratio and cardiac biomarkers, and baseline diastolic function correlates with age. This research was funded by Abbott Laboratories; ClinicalTrials.gov No. NCT00497146.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Activation and Left Ventricular Hypertrophy in Advanced Kidney Disease

Thadhani

Appelbaum²,

Chang

et al. 2011

Am J Nephrol

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“…Due to the relevant role of vitamin D in heart disease, the association between LVH and VDR gene polymorphisms has recently been investigated, and it has been reported that VDR Bsm I gene polymorphism is involved in the development of LVH in ESRD patients [47,48] and is independently related to LVH progression in dialysis patients and in stage IIIb CKD patients. The presence of the Bsm I mutated variant of the VDR gene in ESRD patients has been proposed as a novel marker of disrupted vitamin D signaling pathway, inducing an increase in the LV mass index [48].…”

Section: Pathophysiology Of Lvh In Ckd Patientsmentioning

confidence: 99%

Left Ventricular Hypertrophy in Chronic Kidney Disease Patients: From Pathophysiology to Treatment

Lullo¹,

Gorini²,

Russo³

et al. 2015

Cardiorenal Med

193

154

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Cardiovascular diseases represent the main causes of morbidity and mortality in patients with chronic kidney disease (CKD). According to a well-established classification, cardiovascular involvement in CKD can be set in the context of cardiorenal syndrome type 4. Left ventricular hypertrophy (LVH) represents a key feature to provide an accurate picture of systolic-diastolic left heart involvement in CKD patients. Cardiovascular involvement is present in about 80% of prevalent hemodialysis patients, and it is evident in CKD patients since stage IIIb-IV renal disease (according to the K/DOQI CKD classification). According to the definition of cardiorenal syndrome type 4, kidney disease is detected before the development of heart failure, although timing of the diagnosis is not always possible. The evaluation of LVH is a bit heterogeneous, and few standard imaging methods can provide the accuracy of either CT- or MRI-derived left ventricular mass. Key principles in the treatment of LVH in CKD patients are mainly based on anemia and blood pressure control, together with the management of secondary hyperparathyroidism and sudden cardiac death prevention. This review is mainly focused on the clinical aspects of CKD-related LVH to provide practical guidelines both for cardiologists and nephrologists in the daily clinical approach to CKD patients.

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“…VDR knockout mice exhibit increased LVMI, and human BsmI phenotype is associated with LVMI and LVMI progression (55)(56)(57).…”

Section: Altered Fgf23-klotho Expression and Vitamin D Deficiency As mentioning

confidence: 99%

Reciprocal Control of 1,25-Dihydroxyvitamin D and FGF23 Formation Involving the FGF23/Klotho System

Prié

Friedlander

2010

Clinical Journal of the American Society of Nephrology

115

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agonists is important for the control of phosphate and calcium homeostasis and bone remodeling but could also have beneficial effects by reducing the risk for development of cardiovascular morbidity and mortality, diabetes, autoimmune diseases, and cancer. Microarray assay studies suggested that more than 150 human genes are directly regulated by calcitriol through vitamin D-responsive elements (VDREs) in their promoters (1). Circulating calcitriol is mainly synthesized by the renal proximal tubule. Calcitriol is also produced as an autocrine factor in many tissues. Until recently, parathyroid hormone (PTH) was the main identified peptide known to control calcitriol synthesis in the kidney under physiologic conditions. Ten years ago, genetics analysis of patients with autosomal dominant hypophosphatemic rickets and analysis of tumorinduced osteomalacia resulted in the discovery of fibroblast growth factor 23 (FGF23) (2,3). The sequence of this peptide made it the 23rd member of the FGF family. Rapidly, data accumulated on FGF23 and showed that FGF23 is a hormone that controls serum phosphate concentration and calcitriol metabolism. Klotho, which had been identified a few years earlier, was then recognized as a co-factor that is mandatory for Vitamin D MetabolismVitamin D synthesis in humans begins in the epidermis, where vitamin D 3 is produced from a UVB-mediated conversion of 7-dehydrocholesterol (Figure 1). Vitamin D 3 is then converted to 25(OH)D 3 in the liver, most likely by the high-affinity cytochrome enzyme CYP2R1. Homozygous mutation of CYP2R1 gene is associated with low 25(OH)D 3 circulating concentrations (4). This step is not regulated by hormones. 25(OH)D 3 is released into the plasma and circulates bound mainly to vitamin D-binding protein (DBP). The affinity of DBP for 25(OH)D 3 is very high, and DBP is present

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Vitamin D receptor (VDR) gene polymorphism is associated with left ventricular (LV) mass and predicts left ventricular hypertrophy (LVH) progression in end-stage renal disease (ESRD) patients

Cited by 59 publications

References 27 publications

Vitamin D Receptor Activation and Left Ventricular Hypertrophy in Advanced Kidney Disease

Vitamin D Receptor Activation and Left Ventricular Hypertrophy in Advanced Kidney Disease

Left Ventricular Hypertrophy in Chronic Kidney Disease Patients: From Pathophysiology to Treatment

Reciprocal Control of 1,25-Dihydroxyvitamin D and FGF23 Formation Involving the FGF23/Klotho System

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