Patients with chronic renal impairment often develop thickening of the heart muscle as their disease progresses. The danger of left ventricular hypertrophy is a significant increase in the risk of acute cardiovascular disease such as sudden cardiac death. A recent study has now shown that one risk factor is an increase in fibroblast growth factor 23 (FGF23), which can, however, be influenced by medication.
In particular, late-stage renal failure patients, those who require renal replacement therapy such as hemodialysis, are at risk for developing left ventricular hypertrophy. This is because as kidney function deteriorates, the protein fibroblast growth factor 23 (FGF23) increases. In a randomized controlled trial, a total of 62 patients received either the drug Etelcalcetide (from the drug group of calcimimetics) or Alfacalcidol (vitamin D) over the period of one year. Both drugs are used primarily to treat a bone disease that is common in patients with kidney disease (secondary hyperparathyroidism). The therapy was administered intravenously to patients after each dialysis treatment. Magnetic resonance imaging was used to measure myocardial thickness at the beginning and end of the study. The primary study end point was the change in left ventricular mass index (LVMI; g/m2), measured by cardiac magnetic resonance imaging, from baseline to 12 months. Secondary study endpoints were echocardiographically measured cardiac parameters, biomarker concentrations of bone metabolism (FGF23, vitamin D, parathyroid hormone, calcium, phosphate, s-Klotho), cardiac markers (pro-brain natriuretic peptide, troponin T before and after dialysis), and metabolites of the renin-angiotensin-aldosterone cascade.
It was found that in the etelcalcetide therapy group, FGF23 levels were significantly decreased and myocardial mass remained the same after one year, whereas in patients receiving alfacalcidol therapy, there was an increase in FGF23 and a further increase in myocardial thickening. The PTH, phosphate, and alpha-kotho levels achieved appeared to be similar between treatment arms. Mild hypocalcemia developed in 17% of etelcalcetide and 4% of alfacalcidol users. Mild gastrointestinal problems occurred in 63% vs. 27%. Lowering FGF23 was able to reduce progression of pathological left ventricular hypertrophy by six to eight percent within one year. Effective therapy of this disease could therefore reduce the risk of sudden cardiac death in this population, which already has a significantly increased cardiovascular risk, the authors are certain. In addition, reduced calcium levels could reduce vascular calcification, which in itself is associated with increased risk of LVH and cardiovascular events in hemodialysis patients.
Further reading:
- Dörr K, Kammer M, Reindl-Schwaighofer R, et al: Randomized Trial of Etelcalcetide for Cardiac Hypertrophy in Hemodialysis. Circ Res 2021;128(11): 1616-1625.
- Progression of myocardial thickening in dialysis patients can be slowed down by medication, 22.04.2021, Medical University of Vienna.
CARDIOVASC 2021; 20(2): 19
