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Vitamin D receptor activation and left ventricular hypertrophy in advanced kidney disease
Ravi Thadhani1, Evan Appelbaum, Yuchiao Chang
1Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, USA. thadhani.r@mgh.harvard.edu
Insights
In chronic kidney disease (CKD), left ventricular hypertrophy (LVH) is common. Baseline LVMI correlates with blood pressure, albuminuria, and cardiac biomarkers, while diastolic function relates to age in CKD patients.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Left ventricular hypertrophy (LVH) is a common complication in chronic kidney disease (CKD), significantly increasing cardiovascular risks.
- Vitamin D receptor (VDR) activators have shown potential in preclinical studies to slow LVH progression.
Purpose of the Study:
- To report baseline characteristics of the PRIMO study, evaluating oral paricalcitol in CKD patients with LVH.
- To investigate correlations between baseline left ventricular mass index (LVMI) and cardiovascular risk factors.
Main Methods:
- The PRIMO study is a multinational, randomized, double-blinded trial involving patients with stages 3-4 CKD and mild-to-moderate LVH.
- The primary endpoint is the change in LVMI after 48 weeks, with secondary endpoints focusing on diastolic function.
Main Results:
- Baseline LVMI was higher in males (33.0 ± 7.5 g/m(2.7)) than females (30.8 ± 7.2 g/m(2.7)).
- LVMI showed significant correlations with systolic blood pressure, urine albumin creatinine ratio, troponin T, high-sensitivity C-reactive protein, and B-type natriuretic peptide.
- Early diastolic velocity (E') was inversely correlated with age.
Conclusions:
- Baseline LVMI in CKD patients is associated with blood pressure, albuminuria, and cardiac biomarkers.
- Diastolic function parameters at baseline are influenced by patient age.
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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