Differentially expressed urinary biomarkers in children with idiopathic nephrotic syndrome.

BACKGROUND: We performed a discovery phase of urinary proteomic profile in children with idiopathic nephrotic syndrome and validated selected biomarkers. METHODS: Urinary proteomic profile was performed using isobaric tags for relative and absolute quantitation labeling, coupled with liquid chromatography-matrix assisted laser desorption and ionization analysis. Validation of biomarkers apolipoprotein A1, alpha 2 macroglobulin, orosomucoid 2, retinol binding protein 4 and leucine-rich alpha 2-glycoprotein 1 was done by enzyme-linked immunosorbent assay. RESULTS: Apolipoprotein A1 levels of <0.48 µg/mg of creatinine-differentiated steroid-resistant nephrotic syndrome (SRNS) from first episode nephrotic syndrome, area under curve (AUC) [0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity] and a value of <0.24 µg/mg of creatinine could differentiate SRNS from frequently relapsing nephrotic syndrome/steroid dependent nephrotic syndrome [AUC 0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity]. Alpha 2 macroglobulin could differentiate children with SRNS-focal segmental glomerulosclerosis (FSGS) from SRNS-minimal change disease (MCD) at values >3.3 µg/mg of creatinine [AUC 0.84 (CI 0.62-1.0), 90 % sensitivity and 85 % specificity]. Orosomucoid 2 >1.81 µg/mg of creatinine could distinguish SRNS-FSGS from SRNS-MCD [AUC 0.84 (CI 0.62-1.0), sensitivity 90 % and specificity 85.5 %]. RBP 4 value of >1.54 µg/mg of creatinine differentiated SRNS-FSGS from SRNS-MCD [AUC 0.87 (CI 0.68-1.0), sensitivity 90 % and specificity 85.7 %]. CONCLUSIONS: Lower level of apolipoprotein A1 in urine is suggestive of SRNS. Alpha 2 macroglobulin, retinol binding protein 4 and orosomucoid 2 are markers associated with FSGS, with alpha 2 macroglobulin being most predictive.

Early goal-directed therapy in pediatric septic shock: comparison of outcomes "with" and "without" intermittent superior venacaval oxygen saturation monitoring: a prospective cohort study*.

OBJECTIVE: To evaluate the effect of intermittent central venous oxygen saturation monitoring (ScvO(2)) on critical outcomes in children with septic shock, as continuous monitoring may not be feasible in most resource-restricted settings. DESIGN: Prospective cohort study. SETTING: PICU of a tertiary care teaching hospital. PATIENTS: Consecutive children younger than 17 years with fluid refractory septic shock admitted to our ICU from November 2010 to October 2012 were included. INTERVENTIONS: Enrolled children were subjected to subclavian/internal jugular catheter insertion. Those in whom it was successful formed the "exposed" group (ScvO(2) group), whereas the rest constituted the control group (no ScvO(2) group). In the former group, intermittent ScvO(2) monitoring at 1, 3, and 6 hours was used to guide resuscitation, whereas in the latter, only clinical variables were used. MEASUREMENTS AND MAIN RESULTS: The major outcomes were in-hospital mortality and achievement of therapeutic goals within first 6 hours. One hundred twenty children were enrolled in the study-63 in the ScvO(2) group and 57 in the no ScvO(2) group. Baseline characteristics including the organ dysfunction and mortality risk scores were comparable between the groups. Children in the ScvO(2) group had significantly lower in-hospital mortality (33.3% vs 54%; relative risk, 0.61; 95% CI, 0.4, 0.93; number needed to treat, 5; 95% CI, 3, 27). A greater proportion of children in exposed group achieved therapeutic endpoints in first 6 hours (43% vs 23%, p = 0.02) and during entire ICU stay (71% vs 51%, p = 0.02). The mean number of dysfunctional organs was also significantly lesser in ScvO(2) group in comparison with no ScvO(2) group (2 vs 3, p < 0.001). CONCLUSION: Early goal-directed therapy using intermittent ScvO(2) monitoring seemed to reduce the mortality rates and improved organ dysfunction in children with septic shock as compared with those without such monitoring.

Subclinical non-autoimmune hypothyroidism in children with steroid resistant nephrotic syndrome.

BACKGROUND: Thyroid status has not been studied well in children with steroid resistant nephrotic syndrome (SRNS). METHODS: In this cross sectional study we recruited 20 children aged 1-16 years with SRNS and similar number of controls. Serum levels of FT3, FT4 and TSH were measured in all the subjects. Overt hypothyroidism was defined as low FT4 (normal values: 0.7-2.0 ng/mL) and elevated serum TSH above reference values (0.45-4.5 mIU/L). Subclinical hypothyroidism (SH) was defined as an elevation in serum TSH with a normal serum FT4 concentration. The primary outcome measure was serum levels of FT3, FT4 and TSH in children with SRNS. RESULTS: Thirty per cent of the children (n = 6) with SRNS had non-autoimmune subclinical hypothyroidism (2 children each with grade I, II and III). Children with SRNS had a median TSH value [3.9 mIU/L (0.5-13)] within normal range, but levels were high as compared to controls. Out of 6 children with SH, 3 were in partial remission, 3 were in complete remission. The TSH levels normalized on thyroxine supplementation in grades II and III subclinical hypothyroidism. CONCLUSION: Subclinical non-autoimmune hypothyroidism is present in a significant proportion of children with SRNS despite partial or complete remission. Thyroid profile should be evaluated routinely in this subset of patients.