Safety and efficacy of cinacalcet in children below 3 years of age on maintenance dialysis

Abstract

BackgroundSecondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. While cinacalcet is effective and licensed in dialysis above 3 years, its efficacy and safety below 3 years is unknown. MethodsWe identified 26 children on dialysis below three years treated with cinacalcet between 2009 and 2021 in 8 European pediatric centers. ResultsMedian (IQR) age at start of cinacalcet was 18[IQR 11–27] months, serum parathyroid hormone (PTH) was 792[411–1397] pg/mL, corresponding to 11.6[5.9–19.8] times the upper limit of normal (ULN). Serum calcium was 2.56[2.43–2.75] mmol/L, and serum phosphate 1.47[1.16-1.71] mmol/L. Serum 25-OHD was 70[60–89] nmol/L, three children were vitamin D deficient (<50nmol/L). The initial cinacalcet dose was 0.4[0.2–0.8] mg/kg/day and the maximum dose was 1.1[0.6–1.2] mg/kg/day. The median follow-up under cinacalcet was 1.2[0.7-2.0] years. PTH decreased to 4.3[2.2–7.8] times the ULN after 6 months, to 2.0[1.0–5.3] times ULN after 12 months and to 1.6[0.5–3.4] times thereafter (p=0.017/ 0.003/<0.0001, log-transformed PTH). Seven of the 26 infants developed 10 hypocalcemic episodes <2.10 mmol/L. Oral calcium intake was 84[66-117] % of recommended nutrient intake at start, 100[64-142] % at 3 months and declined to 78[65-102] % at 12 months of therapy. Three children developed clinical signs of precocious puberty. ConclusionCinacalcet efficiently controlled severe sHPT in children below 3 years of age and was associated with hypocalcemic episodes (similarly, to what is observed in older children) and precious puberty, mandating meticulous control of calcium (taking into account nutrition, supplementation and dialysate) and endocrine changes.