ABSTRACT
INTRODUCTION: In last few years, several studies have revealed the remarkable stability of extracellular microRNAs (miRNAs) circulating in the blood or excreted in the urine and underscored their key importance as biomarkers of certain diseases. Since miRNA in urinary sediment is relatively stable and easily quantified, it has the potential to be developed as a biomarker for disease diagnosis and monitoring. Identification of serum and urinary levels of certain miRNAs may assist in the diagnosis and assessment of disease activity in patients with nephrotic syndrome (NS). The global expression profile of miRNAs in childhood NS in Indian population remains unknown. Hence, further research is warranted in this area. This study seeks to prospectively evaluate whether a multipronged multiomics approach concentrating on microRNA expression profiles in children with NS vis-a-vis normal healthy children is discriminant enough to predict steroid responsiveness in childhood NS. METHODS AND ANALYSIS: In this prospective multicentric cohort study, subjects will be recruited from general paediatric and paediatric nephrology outpatient departments (OPDs) in tertiary care level referral hospitals. Age-matched and sex-matched healthy individuals with normal renal function (as assessed by normal serum creatinine and normal ultrasound of kidneys, ureter and bladder) in 1:1 ratio between study and control groups will be recruited from among the healthy siblings of children presenting to the OPDs. Differential microRNA expression profiles in urine and serum samples of children with steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) with healthy children will be compared in a two-phased manner: a biomarker discovery phase involving pooled samples across SSNS, SRNS and healthy siblings analysed in triplicate using next-generation sequencing, slide microarray and quantitative reverse transcriptase PCR (qRT-PCR) arrays covering human miRNome followed by a validation phase with customised qRT-PCR primers based on the concordance in the discovery phase differential expression profiles and bioinformatics analysis. ETHICS AND DISSEMINATION: The study is funded after dueInstitutional Ethics Committee (IEC) clearance, and results will be available as open access.
ABSTRACT
BACKGROUND: The relative effectiveness and safety of sevelamer, a mineral-free phosphate binder, for treatment of hyperphosphatemia in children with chronic kidney disease is uncertain. AIM: This study was designed to compare the efficacy and acceptability of sevelamer hydrochloride to calcium acetate as a phosphate binder in pediatric patients with chronic kidney disease. METHODS: A 12-week open-label trial of sevelamer hydrochloride vs calcium acetate was initiated in 22 patients, aged 2-18, with CKD stages 3 and 4. After a 2-week washout of phosphate binders and vitamin D, patients were randomized to receive sevelamer hydrochloride or calcium acetate. The effect of therapy was adjusted for baseline blood levels of calcium, phosphorus, calcium-phosphate product, alkaline phosphatase, PTH and GFR using ANOVA. The primary end point was the decrease in serum phosphorus levels after 12 weeks of treatment. RESULTS: Of the 22 patients enrolled, data of 19 patients were used for analysis. The adjusted mean serum phosphate levels at 12 weeks did not differ significantly between calcium acetate- (5.3 mg/dl) and sevelamer-treated subjects (6.1 mg/dl) (P adjusted means = 0.6). The adjusted blood level of calcium at 12 weeks was significantly lower in the sevelamer-treated patients (8.2 mg/dl) compared to those treated with calcium acetate (9.1 mg/dl) (P adjusted means = 0.01). In the sevelamer group, there was a non-significant decrease in serum bicarbonate, whereas the total and LDL cholesterol significantly decreased at 12 weeks (P = 0.04). Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug. CONCLUSIONS: Compared to calcium acetate, use of sevelamer in children with chronic kidney disease is associated with similar reduction in serum phosphate levels, lower risk of hypercalcemia, and marked decrease in serum lipid levels.
