Left Ventricular Mass Progression despite Stable Blood Pressure and Kidney Function in Stage 3 Chronic Kidney Disease

Abstract

Background/Aims: Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular (CV) risk not explained by traditional risk factors. Left ventricular (LV) hypertrophy (LVH) is an important CV risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. Methods: We conducted a post hoc analysis of a 12-month study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of CV biomarkers. Primary outcome for the analysis was the change in LV mass (LVM) indexed to height in meters^2.7 (LVM/Ht^2.7). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor 23 (FGF23), klotho, and estimated glomerular filtration rate (eGFR). Results: Thirty-one of 38 original subjects had sufficient data for analysis. LVM/Ht^2.7 increased (47 ± 13 vs. 53 ± 13 g/m^2.7, p = 0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, p = 0.03) but were unrelated to changes in LVM/Ht^2.7. The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht^2.7 (r² = 0.582, p = 0.03). Conclusion: Subjects with stage 3 CKD exhibited increasing LVM, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LVM. These findings deserve further evaluation in a larger population given the adverse prognostic value of these CV biomarkers.

Increased Arterial Stiffness after Coronary Artery Revascularization Correlates with Serious Coronary Artery Lesions and Poor Clinical Outcomes in Patients with Chronic Kidney Disease

“…As Seifert et al [18] have recently reported, patients with stage 3 CKD exhibited increasing left ventricular mass, persistent left ventricular diastolic dysfunction and vascular stiffness, which is consistent with our data. Previous studies have pointed out that Aix and PWV were risk factors for CAD [19,20], while our results also showed a higher occurrence of CAD in patients with high Aix and PWV indexes.…”

Cardiovascular changes in patients with mild‐to‐moderate chronic kidney disease compared with healthy subjects: a 5‐year follow‐up study

“…In our study, we observed no significant increase over time of BP, and no significant change over time in CCA diameter, CIMT, or Ep in the CKD patients. Somehow contradictory to this, a study of 31 patients with Stage 3 CKD observed a progression of LVM over 12 months, despite stable BP and kidney function (Seifert et al, 2014). However, it is possible that the close monitoring of our patients by a dedicated nephrology clinic could have contributed to the lack of progression over time in these cardiovascular parameters.…”

“…Biomarkers including an abnormal ankle-brachial index (ABI), arterial stiffness, increased common carotid artery (CCA) diameter and intima-media thickness (CIMT), and left ventricular hypertrophy (LVH) are associated with increased cardiovascular risks and worse prognosis in CKD (Szeto et al, 2007;Chue et al, 2010;Paoletti et al, 2011;Karras et al, 2012;Kozakova et al, 2017;Chen et al, 2017;Major et al, 2018). Moreover, most of the studies of mildto-moderate CKD have evaluated the deterioration of renal function over time (Baek et al, 2012;Hallan et al, 2012), and few have addressed the longitudinal changes in biomarkers associated with cardiovascular risk (Seifert et al, 2014;Agarwal, 2017). Moreover, most of the studies of mildto-moderate CKD have evaluated the deterioration of renal function over time (Baek et al, 2012;Hallan et al, 2012), and few have addressed the longitudinal changes in biomarkers associated with cardiovascular risk (Seifert et al, 2014;Agarwal, 2017).…”

Cardiac hypertrophy in chronic kidney disease—role of Aldosterone and FGF23

“…More recently, much attention has been focused on the role of FGF23 since this substance not only participates in the phosphate homeostasis but also induces cardiac hypertrophy (Table 3) [21,22,[118][119][120][121][122]. Thus, Gutierrez et al [21] discovered that there existed a close relationship between serum FGF23 levels and LV mass index in patients with CKD.…”