Abstract
Alterations of mineral metabolism in patients with chronic renal failure (MBD-CKD) are frequently found and appear in the earliest stages of the disease. If not accurately diagnosed and treated, they could lead to serious clinical complications. With the same safety and better tolerability compared with cinacalcet, etelcalcetide demonstrated greater efficacy in the control of parathyroid hormone (iPTH) with an improvement in patients' compliance.
Several reports in the literature document the effect of elevated levels of iPTH on anaemia. In vitro experiments showed that elevated concentrations of PTH (comparable to those found in the blood of uraemic patients with secondary hyperparathyroidism) exert a significant inhibition on erythroid progenitors, decreasing the number of erythropoietin receptors on erythroid progenitors and making these cells insensitive to erythropoietin.
High levels of iPTH could have, furthermore, a haemolytic effect on the peripheral RBCs causing disturbed calcium metabolism, increased cytosolic calcium and enhanced osmotic fragility of the cells.
Aim of this study was to verify in a dialysis cohort if etelcalcetide could not only improve iPTH levels but also haemoglobin levels with a reduction in weekly doses of erythropoiesis-stimulating agents (ESA).
We analysed data from 130 haemodialysis adult patients over 2 years from three different centres. A total of 24 patients treated with etelcalcetide (Image 1) were enrolled and followed at different time points (1–3–6–12–24 months). Patients were on stable doses of ferric carboxymaltose, active vitamin D analogues, phosphorus binders, supplement of oral calcium and calcium concentration in dialysate (1.25–1.50 mmol/L).
Data analysed after 24 months of treatment with etelcalcetide (Image 2) demonstrated not only a drastic improvement in iPTH values (772.53 ± 452.6 pg/mL versus 308.7 ± 207 pg/mL–60.05%) but also a statistically significant improvement of haemoglobin values ( 10.35 ± 1.45 g/dL versus 11.57 ± 0.97 g/dL; P < .05) in addition to a reduction in the weekly ESAs units required (193.39 ± 148 UI/kg/week versus 142.71 ± 118 UI/kg/week; P < .05). This effect was achieved by maintaining constant ferritin and TSAT levels and without substantial changes in iron carboxymaltose therapy. No side effects were recorded for the entire duration of the treatment.
Considering the well-known direct and indirect inhibition of parathyroid hormone on erythropoiesis, reduction of iPTH levels achieved with etelcalcetide could improve haemoglobin levels and reduce required weekly ESA units, with obvious clinical and economic advantages. Further studies, on large populations and over longer periods of time, are required.
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