Cinacalcet as rescue therapy for refractory hyperparathyroidism in young children with advanced chronic kidney disease.

BACKGROUND: Studies in the use of the calcimimetic, cinacalcet, in pediatric chronic kidney disease (CKD) are few and limited to older children with secondary hyperparathyroidism (sHPT), a major morbid complication contributing to poor growth, bone deformities, and cardiovascular disease. Our objectives were to determine a safe and effective dosing regimen of cinacalcet in the treatment of infants and young children with sHPT that was refractory to standard care and to examine their growth during treatment. METHODS: Ten young pediatric patients with advanced CKD were studied retrospectively during 11 courses of treatment with cinacalcet. All had severe sHPT with intact parathyroid hormone (iPTH) levels ≥ 500 pg/ml and were refractory to standard therapy with phosphate binders and active vitamin D analogs at high doses for > 30 days. The cinacalcet dose was advanced by 50% every 2-4 weeks to achieve a decline in the iPTH to a goal of 150-300 pg/ml. Linear growth was assessed at 6-month intervals by change in z-scores (△SDS) for length before and during cinacalcet therapy. RESULTS: Median age at initiation of cinacalcet was 18 months (IQR 6, 36) with an average starting dose of 0.7 ± 0.2 mg/kg/day. Median effective dose required to reach iPTH goal of 150-300 pg/ml was 2.8 mg/kg/day (IQR 2.0, 3.1), and time to goal was 112 days (IQR 56, 259) with a median overall decline in iPTH of 82% from baseline by 6 months (p < 0.0001). No subject experienced a clinical adverse event, although 4 had biochemical asymptomatic hypocalcemia. Linear growth improved significantly during cinacalcet therapy (△SDS - 0.62 ± 1.2 versus + 0.91 ± 1.4; p < 0.005). By multiple regression analysis, the primary determinants of growth were concurrent treatment with growth hormone and age < 2 years (R2 = 89.6%; p < 0.001). A shorter treatment time required to achieve iPTH goals also was associated with improved growth (r = - 0.75; p < 0.01). CONCLUSIONS: Cinacalcet may be used effectively and safely in infants and small children with refractory sHPT in advanced CKD using a cautious dosing regimen. Cinacalcet successfully brings iPTH to target level and supports growth when other treatments have been ineffective.

Comparison of echocardiographic changes in children with primary hypertension and hypertension due to mild to moderate chronic kidney disease.

BACKGROUND: Chronic systemic hypertension has a well-known association with increased cardiovascular morbidity and mortality. One of the most important target organs affected in systemic hypertension is the heart. In addition, chronic kidney disease (CKD) further increases the mortality from cardiovascular disease. The aim of this study was to evaluate the differences in the cardiovascular changes in pediatric patients with primary hypertension (pHTN) vs. those with secondary hypertension from chronic kidney disease (CKD-HTN). METHODS: This was a retrospective chart review of patients with CKD-HTN and pHTN. The medical records were reviewed for anthropometric data, biochemical assessment of renal function, and for cardiovascular changes on echocardiogram. RESULTS: Twenty-three patients with pHTN and 29 patients with CKD-HTN were included in the study. There were no differences in age, gender, weight, height, body mass index, and blood pressure between the 2 groups. There was a high prevalence of left ventricular diastolic dysfunction among both the groups (CKD-HTN 25 vs. pHTN 26%). Reduced mitral valve inflow Doppler E/A ratio, a marker of left ventricular diastolic dysfunction in echocardiogram, was more pronounced in CKD-HTN patents, in comparison to those with pHTN (p = 0.042). Also, diastolic function worsened with declining glomerular filtration rate in patients with CKD-HTN. Similarly, patients with CKD-HTN had a larger aortic root dimension when compared to patients with pHTN (p = 0.049). CONCLUSIONS: The prevalence of left ventricular diastolic dysfunction is similar in patients with pHTN and CKD-HTN. Patients with CKD-HTN appear to have more severe diastolic dysfunction and larger aortic root dimensions.