Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis.

Introduction: Secondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. Although cinacalcet is effective and licensed in dialysis in children aged >3 years, its efficacy and safety for children aged <3 years is unknown. Methods: We identified 26 children aged <3 years who were on dialysis and treated with cinacalcet between 2009 and 2021 in 8 European pediatric centers. Results: Median (interquartile range) age at the start of cinacalcet was 18 (interquartile range: 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-OH vitamin D (25-OHD) was 70 (60-89) nmol/l, 3 children were vitamin D deficient (<50 nmol/l). The initial cinacalcet dose was 0.4 (0.2-0.8) mg/kg/d and the maximum dose was 1.1 (0.6-1.2) mg/kg/d. 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. Conclusion: Cinacalcet efficiently controlled severe sHPT in children aged <3 years and was associated with hypocalcemic episodes (similar to what is observed in older children) and precious puberty, thereby mandating meticulous control of calcium (considering nutrition, supplementation, and dialysate) and endocrine changes.

Ten tips on how to assess bone health in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) experience a several-fold increased risk of fracture. Despite the high incidence and the associated excess morbidity and premature mortality, bone fragility in CKD, or CKD-associated osteoporosis, remains a blind spot in nephrology with an immense treatment gap. Defining the bone phenotype is a prerequisite for the appropriate therapy of CKD-associated osteoporosis at the patient level. In the present review, we suggest 10 practical 'tips and tricks' for the assessment of bone health in patients with CKD. We describe the clinical, biochemical, and radiological evaluation of bone health, alongside the benefits and limitations of the available diagnostics. A bone biopsy, the gold standard for diagnosing renal bone disease, is invasive and not widely available; although useful in complex cases, we do not consider it an essential component of bone assessment in patients with CKD-associated osteoporosis. Furthermore, we advocate for the deployment of multidisciplinary expert teams at local, national, and potentially international level. Finally, we address the knowledge gaps in the diagnosis, particularly early detection, appropriate "real-time" monitoring of bone health in this highly vulnerable population, and emerging diagnostic tools, currently primarily used in research, that may be on the horizon of clinical practice.

Denosumab in a pediatric kidney transplant recipient with late, resistant hypercalcemia secondary to Pneumocystis jirovecii pneumonia.

Kidney transplant recipients (KTR) are at an increased risk of developing Pneumocystis jirovecii pneumonia (PCP), especially during the first year after transplantation. This is the first reported pediatric KTR, with chronic kidney disease (CKD) secondary to kidney dysplasia and vesicoureteral reflux, who developed refractory and symptomatic hypercalcemia 5 years after transplantation. The hypercalcemia was resistant to treatment with intravenous hyperhydration, furosemide, and a low-calcium diet. A respiratory tract infection due to PCP treated with trimethoprim-sulfamethoxazole did not improve calcium levels. Due to the hypercalcemic symptom burden for the patient, a single dose of subcutaneous denosumab was used to achieve sustained clinical and biochemical improvement, without any severe adverse events. This case highlights the potential use of denosumab as a treatment option in pediatric KTR with refractory hypercalcemia related to PCP. Further study of denosumab in young people with CKD or kidney transplants is needed before routine use can be recommended.