Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease.

AIMS: The prevalence of vitamin D deficiency is high in children with chronic kidney disease (CKD). However, current dosing recommendations are based on limited pharmacokinetic (PK) data. This study aimed to develop a population PK model of colecalciferol that can be used to optimise colecalciferol dosing in this population. METHODS: Data from 83 children with CKD were used to develop a population PK model using a nonlinear mixed effects modelling approach. Serum creatinine and type of kidney disease (glomerular vs. nonglomerular disease) were investigated as covariates, and optimal dosing was determined based on achieving and maintaining 25-hydroxyvitamin D (25(OH)D) concentration of 30-48 ng/mL. RESULTS: The time course of 25(OH)D concentrations was best described by a 1-compartment model with the addition of a basal concentration parameter to reflect endogenous 25(OH)D production from diet and sun exposure. Colecalciferol showed wide between-subject variability in its PK, with total body weight scaled allometrically the only covariate included in the model. Model-based simulations showed that current dosing recommendations for colecalciferol can be optimised using a weight-based dosing strategy. CONCLUSION: This is the first study to describe the population PK of colecalciferol in children with CKD. PK model informed dosing is expected to improve the attainment of target 25(OH)D concentrations, while minimising the risk of overdosing.

Chronic Kidney Disease (CKD): An Observational Study of Etiology, Severity and Burden of Comorbidities.

OBJECTIVES: To study the etiology and burden of comorbidities across stages of chronic kidney disease (CKD). METHODS: Children, 2-16 y of age with CKD Stages II- IV were recruited over 12 mo. The etiology, clinical presentation and severity of complications were studied. RESULTS: Among 78 children [Stage II (n = 21), Stage III (n = 26), Stage IV (n = 31)], congenital anomalies of the kidney and urinary tract (CAKUT) was the commonest etiology and 28 were newly diagnosed in Stage III /IV. High prevalence of comorbidities was observed with growth retardation (65%), hypertension (59%), hyperphosphatemia (32%), vitamin D deficiency (92%), dyslipidemia (64%), left ventricular hypertrophy (45%) and hyperparathyroidism (56%). While most comorbidities correlated with the estimated glomerular filtration rate and severity of CKD, hypertension, vitamin D deficiency and cardiovascular morbidity were prevalent even in early stages. CONCLUSIONS: CAKUT was the commonest cause of CKD. Late detection and high prevalence of comorbidities even in early stages of CKD were observed.

Proteinuria in children with juvenile idiopathic arthritis: Making the case for early urinary screening.

Systemic onset juvenile idiopathic arthritis (SOJIA) can be associated with proteinuria due to various renal pathologies. We report two pediatric cases with SOJIA and nephrotic syndrome secondary to renal amyloidosis, a very rare complication in children. Once present, amyloidosis heralds a poor prognosis for the patient, though early detection may allow some improvement if the inflammatory arthritis is controlled.