Biomarkers for Regression/Progression of Left Ventricular Hypertrophy in ESRD

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Chan CT, Kaysen GA, Beck GJ, Li M, Lo J, Rocco MV, Kliger AS: Changes in Biomarker Profile and Left Ventricular Hypertrophy Regression: Results from the Frequent Hemodialysis Network Trials: Am J Nephrol 2018;47:208–217

Left ventricular hypertrophy (LVH) is common in chronic kidney disease (CKD) and in end-stage renal disease (ESRD) treated by dialysis. The failure of LVH to regress or its progression can be associated with a high risk of mortality, especially that due to sudden cardiac death. The Frequent Hemodialysis Network (FHN) trials of daily or nocturnal hemodialysis (HD) have suggested that these forms of dialysis have the potential to benefit LVH compared to conventional HD. Better control of fluid volume status and blood pressure (BP) have been suggested to explain these findings, but the mechanisms involved remain not well understood.

Chan and co-workers have conducted a post-hoc analysis of the FHN trials to see if biomarkers can predict the changes in LVH in dialysis treated ESRD. Of 243 subjects with complete data, the LVH regressed in 77, progressed in 45 and neither regressed or progressed in 121. Regression LVH was highly associated with more frequent HD and lower levels of systolic and diastolic BP. In addition, serum Klotho levels increased and tissue inhibitor of metalloproteinase-2 (TIMP-2) decreased in association with regression of LVH. Changes in LVH were inversely associated with changes in serum Klotho levels (see Figure 1). Fibroblast Growth Factor 23 (FGF23) and serum phosphorous levels were not consistently associated with regression of LVH, although these levels tended to increase among repressors and decrease in progressors. Serum B-natriuretic peptide levels (a marker of volume status) declined in association with LVH regression. The differences in serum aldosterone levels (after adjustment for serum potassium and BP) did not differ in regressors compared to progressors. Copeptin levels tended to increase in progressors and decline in regressors.

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Figure 1: Association between changes in Klotho and changes in left ventricular mass (LVM) (r = –0.24, p = 0.014; red circles denote regressors, blue circles denote progressors). From Am J Nephrol 2018;47:208–217

Although this study is largely exploratory and hypothesis-generating, it does point in a new direction for future examination of the mechanisms underlying the benefits of more-frequent HD in control of the lethal consequences of LVH in ESRD. The FGF23 studies are interesting since this bone-derived hormone has been suggested to play a role in LVH of ESRD.

The findings concerning Klotho and TIMP-2 are novel and deserve further exploration as they support a role for extracellular matrix homeostasis in LVH of ESRD and may give rise to new therapeutic opportunities.

Richard Glassock

Quoted Karger Article


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