On the basis of observational studies, the most common cause of nephrotic syndrome in school-aged children is minimal change disease. On the basis of research evidence and consensus, corticosteroids are considered first-line therapy for treatment of nephrotic syndrome. On the basis of consensus, prednisone therapy should be initiated at doses of 60 mg/m2 per day (2 mg/kg per day) administered for 4 to 6 weeks, followed by 40 mg/m2 per dose (1.5 mg/kg) every other day for at least 6 to 8 weeks. On the basis of consensus and expert opinion, it is important to recognize and manage the complications that can arise in patients with nephrotic syndrome, such as dyslipidemia, infection, and thrombosis. On the basis of research evidence, consensus, and expert opinion, several alternative therapies have been observed to have variable efficacy in children with both corticosteroid-dependent and corticosteroid-resistant nephrotic syndrome, although caution must be exercised in the administration of these corticosteroid-sparing medications secondary to toxic adverse effects. On the basis of observational studies, the course of nephrotic syndrome in most patients is that of relapse and remission.

Correction of anemia with erythropoietin (EPO) is associated with improved kidney transplant outcomes. Emerging evidence, predominantly from animal models, indicates that these observations may be erythropoiesis-independent and that EPO exhibits immunosuppressive properties. We examined the effects of EPO on human T-cell alloimmunity by first documenting that CD4 + and CD8 + T cells express EPO receptor (EPO-R) on their surfaces. In mixed lymphocyte reactions, EPO induced a dose-dependent decrease in allogeneic CD4 + T-cell proliferation (EPO 1000 U/ml: 44.6%622.9% of vehicle, P,0.05; 2000 U/ml: 11.1%64% of vehicle, P,0.001) without inducing cell death. The effects required signals transmitted directly through the EPO-R expressed on T cells, resulting in diminished Th1 differentiation without effects on regulatory T-cell induction. Mechanistic studies revealed that EPO prevented IL-2-induced proliferation by uncoupling IL-2 receptor signaling, inhibiting phosphorylation of the intracellular intermediaries AKT and extracellular signal-regulated kinase that are known to mediate T-cell expansion. EPO treatment reduced expansion of human naïve CD4 + T cells after adoptive transfer into NOD scid gc null mouse recipients, verifying the effects in vivo. Although activated T cells expressed CD131, an alternative EPO receptor, addition of a specific CD131 agonist peptide, ARA290, did not alter T-cell proliferation or cytokine production. Our findings link EPO-R signaling on T cells to inhibition of T-cell immunity, providing one mechanism that could explain the observed protective effects of EPO in kidney transplant recipients. The anemia that commonly occurs in kidney transplant recipients has been hypothesized to contribute to chronic allograft injury, in part by limiting oxygen delivery to the tubulointersitium and as a consequence, enabling fibrogenesis. 1 In support of a link between anemia and kidney allograft injury, results of a 2012 randomized controlled study of erythropoietin (EPO) therapy after transplantation showed that targeting hemoglobin values to a normal range of $13 g/dl slowed progression of chronic allograft nephropathy and prolonged graft survival compared with partial correction of anemia. 2 Although the above-cited clinical study and selected studies in rodents indicate correlations between EPO-induced increases in hematocrit and reduced tubulointerstitial damage as well as preserved renal tubular cells and improved kidney function, 3 direct evidence linking EPO-induced erythropoiesis to better transplant outcomes is lacking. In fact, experiments performed in a fully mismatched rat kidney transplant model showed that EPO, but not the correction of anemia by blood transusion, limits chronic allograft injury, 4,5 supporting the conclusion that the transplant-protective effects of EPO do not require an EPO-induced increase in hematocrit. Among potential alternative mechanisms, emerging evidence from animal models suggests that

Practice Gap Pediatricians must be aware of screening indications and the evaluation and management of a child with hematuria and/or proteinuria. Objectives After completing this article, readers should be able to: 1. Understand the common causes of proteinuria and hematuria and be able to differentiate between benign and serious causes. 2. Describe screening techniques for initial evaluation of hematuria and proteinuria. 3. Recognize the criteria for diagnosis of proteinuria and hematuria. 4. Plan the appropriate initial evaluation for hematuria and proteinuria and interpret laboratory findings essential for diagnosis. 5. Recognize serious causes of hematuria and proteinuria that warrant immediate referral.

IntroductionMeasuring the chemokine CXCL9 in urine by enzyme-linked immunosorbent assay (ELISA) can diagnose acute cellular rejection (ACR) noninvasively after kidney transplantation, but the required 12- to 24-hour turnaround time is not ideal for rapid, clinical decision-making.MethodsWe developed a biolayer interferometry (BLI)−based assay to rapidly measure urinary CXCL9 in <1 hour. We validated this new assay versus standard ELISA in 86 urine samples from kidney transplantation recipients with various diagnoses. We then used BLI to analyze samples from 56 kidney transplantation recipients, including 46 subjects who experienced an acute rise in serum creatinine associated with biopsy-proven ACR (n = 22), subclinical rejection (n = 15), or no infiltrates (n = 9), and 10 stable kidney transplantation recipients with surveillance biopsies. To assess its usefulness in detecting adequacy of therapy we serially measured serum creatinine and urinary CXCL9 in 6 subjects after treatment for ACR, and correlated the results with histological diagnoses on follow-up biopsies.ResultsBLI accurately and reproducibly detected urinary CXCL9 in <1 hour. BLI-based results showed that urinary CXCL9 was >200 pg/ml in subjects with ACR and ≤100 pg/ml in subjects with stable kidney function without cellular infiltrates. In samples obtained after treatment for ACR, BLI CXCL9 measurements detected biopsy-proven intragraft infiltrates despite treatment-induced reduction in serum creatinine.DiscussionTogether, our proof-of-principle results demonstrate that BLI-based urinary CXCL9 detection has potential as a point-of-care noninvasive biomarker to diagnose and guide therapy for ACR in kidney transplantation recipients.

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