Disclosure: The authors declare no conflict of interest. 1. Research is needed to focus on evaluating the validity and outcome associations of different methods of defining baseline SCr in neonates, which consider the physiological changes occurring in SCr in early neonatal life 2. Research is needed to develop SCr-based neonatal AKI definitions by studying newborn infants at varying gestational and postnatal ages, from the first few weeks of life, compared with older age groups 3. Studies evaluating neonatal AKI and long-term outcomes should be powered to evaluate the association between at least stage 2 AKI and outcomes Use of urine output change as a criterion for defining AKI in newborn infants 4. Research is needed to further evaluate urine output-defined AKI in neonatal AKI studies, including comparison with SCr-AKI definition and outcome associations 5. Research is needed to define "volume overload" or "change in volume status/balance" by evaluating and comparing studies that precisely measured urine output and incorporating the findings in the definition of neonatal AKI 6. Urine output and/or volume overload-based neonatal AKI definitions need to be evaluated in neonates of varying gestational and postnatal ages, comparing the first week of life with later periods Use of other serum and urine biomarkers for a neonatal AKI definition 7. Future studies need to evaluate novel AKI biomarkers in neonates for AKI diagnosis and prediction of short-and long-term neonatal outcomes 8. Studies are needed to elucidate neonatal clinical and physiologic factors that affect AKI biomarker concentrations independent of renal function

Glucocorticoids are the primary therapy for nephrotic syndrome (NS), but have serious side effects and are ineffective in ~20–50% of patients. Thiazolidinediones have recently been suggested to be renoprotective, and to modulate podocyte glucocorticoid-mediated nuclear receptor signaling. We hypothesized that thiazolidinediones could enhance glucocorticoid efficacy in NS. We found that puromycin aminonucleoside-induced proteinuria in rats was significantly reduced by both high-dose glucocorticoids (79%) and pioglitazone (61%), but not low-dose glucocorticoids (25%). Remarkably, pioglitazone + low-dose glucocorticoids also reduced proteinuria (63%) comparably to high-dose glucocorticoids, whereas pioglitazone + high-dose glucocorticoids reduced proteinuria to almost control levels (97%). Molecular analysis revealed that both glucocorticoids and pioglitazone enhanced glomerular synaptopodin and nephrin expression, and reduced COX-2 expression, after injury. Furthermore, the glomerular phosphorylation of glucocorticoid receptor and Akt, but not PPARγ, correlated with treatment-induced reductions in proteinuria. Notably, clinical translation of these findings to a child with refractory NS by the addition of pioglitazone to the treatment correlated with marked reductions in both proteinuria (80%) and overall immunosuppression (64%). These findings together suggest that repurposing pioglitazone could potentially enhance the proteinuria-reducing effects of glucocorticoids during NS treatment.

Background and objectivesNephrotic syndrome (NS) represents a common disease in pediatric nephrology typified by a relapsing and remitting course and characterized by the presence of edema that can significantly affect the health-related quality of life in children and adolescents. The PROMIS pediatric measures were constructed to be publically available, efficient, precise, and valid across a variety of diseases to assess patient reports of symptoms and quality of life. This study was designed to evaluate the ability of children and adolescents with NS to complete the PROMIS assessment via computer and to initiate validity assessments of the short forms and full item banks in pediatric NS. Successful measurement of patient reported outcomes will contribute to our understanding of the impact of NS on children and adolescents.DesignThis cross-sectional study included 151 children and adolescents 8-17 years old with NS from 16 participating institutions in North America. The children completed the PROMIS pediatric depression, anxiety, social-peer relationships, pain interference, fatigue, mobility and upper extremity functioning measures using a web-based interface. Responses were compared between patients experiencing active NS (n = 53) defined by the presence of edema and patients with inactive NS (n = 96) defined by the absence of edema.ResultsAll 151 children and adolescents were successfully able to complete the PROMIS assessment via computer. As hypothesized, the children and adolescents with active NS were significantly different on 4 self-reported measures (anxiety, pain interference, fatigue, and mobility). Depression, peer relationships, and upper extremity functioning were not different between children with active vs. inactive NS. Multivariate analysis showed that the PROMIS instruments remained sensitive to NS disease activity after adjusting for demographic characteristics.ConclusionsChildren and adolescents with NS were able to successfully complete the PROMIS instrument using a web-based interface. The computer based pediatric PROMIS measurement effectively discriminated between children and adolescents with active and inactive NS. The domain scores found in this study are consistent with previous reports investigating the health-related quality of life in children and adolescents with NS. This study establishes known-group validity and feasibility for PROMIS pediatric measures in children and adolescents with NS.

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