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Observational Study
. 2018;47(3):208-217.
doi: 10.1159/000488003. Epub 2018 Apr 5.

Changes in Biomarker Profile and Left Ventricular Hypertrophy Regression: Results from the Frequent Hemodialysis Network Trials

Christopher T Chan  1 , George A Kaysen  2 , Gerald J Beck  3 , Minwei Li  3 , Joan Lo  4 , Michael V Rocco  5 , Alan S Kliger  6 ; FHN Trials
Affiliations
Observational Study

Changes in Biomarker Profile and Left Ventricular Hypertrophy Regression: Results from the Frequent Hemodialysis Network Trials

Christopher T Chan et al. Am J Nephrol. 2018.

Abstract

Background: Regression of left ventricular hypertrophy (LVH) is feasible with more frequent hemodialysis (HD). We aimed to ascertain pathways associated with regression of left ventricular mass (LVM) in patients enrolled in the Frequent HD Network (FHN) trials.

Methods: This was a post hoc observational cohort study. We hypothesized LVH regression with frequent HD was associated with a different cardiovascular biomarker profile. Regressors were defined as patients who achieved a reduction of more than 10% in LVM at 12 months. Progressors were defined as patients who had a minimum of 10% increase in LVM at 12 months.

Results: Among 332 randomized patients, 243 had biomarker data available. Of these, 121 patients did not progress or regress, 77 were regressors, and 45 were progressors. Mean LVM change differed between regressors and progressors by -65.6 (-74.0 to -57.2) g, p < 0.001. Regressors had a median (interquartile range) increase in dialysis frequency (from 3.0 [3.0-3.0] to 4.9 [3-5.7] per week, p = 0.001) and reductions in pre-dialysis systolic (from 149.0 [136.0-162.0] to 136.0 [123.0-152.0] mm Hg, p < 0.001) and diastolic (from 83.0 [71.0-91.0] to 76.0 [68.0-84.0] mm Hg, p < 0.001) blood pressures. Klotho levels increased in regressors versus progressors (76.9 [10.5-143.3] pg/mL, p = 0.024). Tissue inhibitors of metalloproteinase (TIMP)-2 levels fell in regressors compared to progressors (-7,853 [-14,653 to -1,052] pg/mL, p = 0.024). TIMP-1 and log (brain natriuretic -peptide [BNP]) levels also tended to fall in regressors. Changes in LVM correlated inversely with changes in klotho (r = -0.24, p = 0.014). -Conclusions: Markers of collagen turnover and changes in klotho levels are potential novel pathways associated with regression of LVH in the dialysis population, which will require further prospective validation.

Trial registration: ClinicalTrials.gov NCT00264758 NCT00271999.

Keywords: Copeptin; Brain natriuretic peptide; Cardiac biomarkers; Frequent hemodialysis; Klotho; Left ventricular hypertrophy; Markers of collagen turnover.

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Conflict of interest statement

CONFLICT OF INTEREST: Joan Lo has received past research funding from Amgen and Sanofi unrelated to this study.

Figures

Figure 1
Figure 1
Association between changes in Klotho and changes in left ventricular mass (r = −0.24, p = 0.014) [red circles denote regressors, blue circles denote progressors]
Figure 2
Figure 2
Association between changes in log of brain natriuretic peptide and changes in left ventricular mass (r = 0.32, p = 0.013) [red circles denote regressors, blue circles denote progressors]
See this image and copyright information in PMC

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