Clinical Experience of a Long-acting Pegylated Erythropoietin-Stimulating Agent in Pediatric Chronic Kidney Disease.

OBJECTIVE: Management of anemia of chronic kidney disease (CKD) often includes subcutaneous or intravenous administration of erythropoietin-stimulating agents (ESAs). Mircera, a pegylated continuous erythropoietin receptor agonist, has a longer duration of action and requires less frequent administration than other ESAs. Pediatric experience with Mircera is limited. We retrospectively reviewed our long-term experience of Mircera in a national pediatric nephrology center. METHODS: Patients were identified via an electronic patient record database. Data collected included demographics (sex, age, etiology of CKD, CKD stage, dialysis modality), dosing information, and laboratory data-hemoglobin (Hb), parathormone (PTH), ferritin, hematinics prior to commencing Mircera and all subsequent values associated with dose adjustments. RESULTS: Seventy-seven patients aged 2 to 18 years, with CKD stages 2 to 5T had received at least 1 dose of Mircera, with 75 patients having sufficient data and a total of 1473 doses. No patients discontinued Mircera owing to adverse effects. One patient experienced a potential severe adverse drug reaction. Mircera was effective in improving or maintaining Hb ≥10.0 g/dL in most (58/75, 77.3%) patients. The median dose to achieve Hb ≥10.0 g/dL was 2.1 µg/kg/4 wk. Most doses (1039, 71.5%) were administered 4-weekly. The doses (161, 11.1%) that were administered 6-weekly remained efficacious. Thirty-two patients started Mircera with Hb <10.0 g/dL; 26 (81%) achieved Hb ≥10.0 g/dL within a median time of 4 months. Mircera was less effective if given every 8 weeks, or in the presence of hyperparathyroidism or hyperferritinemia. CONCLUSION: Mircera appears safe and effective in pediatric patients with CKD.

Association of Time-Varying Blood Pressure With Chronic Kidney Disease Progression in Children.

Importance: Optimal blood pressure (BP) management in children with chronic kidney disease (CKD) slows progression to end-stage renal disease. Studies often base progression risk on a single baseline BP measurement, which may underestimate risk. Objective: To determine whether time-varying BP measurements are associated with a higher risk of progression of CKD than baseline BP measurements. Design, Setting, and Participants: The ongoing longitudinal, prospective cohort study Chronic Kidney Disease in Children (CKID) recruited children from January 19, 2005, through March 19, 2014, from pediatric nephrology centers across North America, with data collected at annual study visits. Participants included children aged 1 to 16 years with a diagnosis of CKD and a glomerular filtration rate (GFR) of 30 to 90 mL/min/1.73 m2. Data were analyzed from February 11, 2005, through February 13, 2018. Exposures: Office BP measurement classified as less than 50th percentile, 50th to less than 90th percentile, or at least 90th percentile. Blood pressure categories were treated as time fixed (baseline) or time varying (updated at each visit) in models. Main Outcomes and Measures: A composite renal outcome (50% GFR reduction from baseline, estimated GFR less than 15 mL/min/1.73 m2, or dialysis or transplant). Pooled logistic models using inverse probability weighting estimated the hazard odds ratio (HOR) of the composite outcome associated with each BP category stratified by CKD diagnosis. Results: A total of 844 children (524 [62.1%] male; median age, 11 [interquartile range, 8-15] years; 151 [17.9%] black; 580 [68.7%] with nonglomerular CKD; and 264 [31.3%] with glomerular CKD) with complete baseline data and median follow-up of 4 (interquartile range, 2-6) years were included. One hundred ninety-six participants with nonglomerular diagnoses (33.8%) and 99 with glomerular diagnoses (37.5%) reached the composite outcome. Baseline systolic BP in at least the 90th percentile was associated with a higher risk of the composite outcome (HOR for nonglomerular disease, 1.58 [95% CI, 1.07-2.32]; HOR for glomerular disease, 2.85 [95% CI, 1.64-4.94]) compared with baseline systolic BP in less than the 50th percentile. Time-fixed estimates were substantially lower compared with time-varying systolic BP percentile categories (HOR among those with nonglomerular CKD, 3.75 [95% CI, 2.53-5.57]; HOR among those with glomerular diagnoses, 5.96 [95% CI, 3.37-10.54]) comparing those at or above the 90th percentile vs below the 50th percentile. Adjusted models (adjusted for proteinuria and use of antihypertensives) attenuated the risk in nonglomerular CKD (adjusted HOR for baseline measurement, 1.52 [95% CI, 0.98-2.36]; adjusted HOR for time-varying measurement, 2.25 [95% CI, 1.36-3.72]) and in glomerular CKD (adjusted HOR for baseline, 0.97 [95% CI, 0.39-2.36]; adjusted HOR for time-varying measurement, 1.41 [95% CI, 0.65-3.03]). Similar results were observed for diastolic BP. Conclusions and Relevance: Among children with nonglomerular CKD included in this study, elevated time-varying BP measurements were associated with a greater risk of CKD progression compared with baseline BP measurement. This finding suggests that previous studies using only baseline BP likely underestimated the association between BP and CKD progression.

Diagnostic and Management Challenges in Congenital Nephrotic Syndrome.

Congenital Nephrotic Syndrome (CNS) is defined as nephrotic range proteinuria, hypoalbuminaemia and edema in the first three months of life. CNS is most commonly genetic in cause, with international variance in the incidence of causative mutations. Initially defined by the histopathological appearance, increasingly sophisticated and accessible genetic analyses now provide a body of evidence to suggest that there is a disparity between the histological appearance, the genotype of individuals and the severity of the clinical disease. Through the evolution of management approaches CNS has changed from being an invariably fatal condition to one with appreciable ongoing morbidity and mortality but comparably good outcomes to other causes of paediatric end-stage renal disease, especially following transplantation. This review briefly summarises the more commonly recognised genetic mutations leading to CNS, addresses common management decisions, and concludes with potential therapies for the future.

Renal and Adrenal Ultrasonography: a valuable diagnostic tool in the salt-wasting infant.

UNLABELLED: The major differential diagnosis in 'salt-wasting' infants (characterised by hyponatraemia and hyperkalaemia) is that of an adrenal or renal disorder. Appropriate management relies on rapid diagnosis, but existing guidelines do not highlight the role of ultrasonography. We describe how ultrasound may lead to a more rapid diagnosis in disorders of sex development (DSD) and other potential 'salt-wasting' infants. CONCLUSION: Ultrasonography as a diagnostic tool in infants with salt-wasting or DSD needs to be more widely recognised.

Domiciliary administration of intravenous albumin in congenital nephrotic syndrome.

BACKGROUND: Early management of congenital nephrotic syndrome invariably includes the frequent administration of intravenous human albumin solution. The safety and feasibility of intravenous administration of albumin in the patients' home setting has not previously been reported. CASE-DIAGNOSIS/TREATMENT: We report a series of seven paediatric patients whose parents were trained in the administration of albumin via a central venous catheter at home, with the aim of minimising hospital admission or attendances. We describe the clinical course of these patients and complication rates ascribed to this strategy. CONCLUSIONS: Our results demonstrate that home albumin infusion can be performed safely.

Goitrous congenital hypothyroidism in a twin pregnancy causing respiratory obstruction at birth: implications for management.

We report a twin pregnancy complicated by fetal goitrous hypothyroidism secondary to dyshormonogenesis caused by thyroglobulin deficiency. Antenatal treatment with intra-amniotic thyroxine was considered but not performed, given the late gestational age at diagnosis and the multiple nature of the pregnancy. Both twins developed airway obstruction at delivery, requiring intubation and ventilation. We review the literature and describe the practical issues relating to the antenatal assessment and perinatal management of fetal goitre.