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Background: Despite the common use of mycophenolate in pediatric renal transplantation, lack of effective therapeuic drug monitoring increases uncertainty over optimal drug exposure and risk for adverse reactions. This study aims to develop a novel urine test to estimate MPA exposure based using metabolomics. Methods: Urine samples obtained on the same day of MPA pharmacokinetic testing from two prospective cohorts of pediatric kidney transplant recipients were assayed for 133 unique metabolites by mass spectrometry. Partial least squares (PLS) discriminate analysis was used to develop a top 10 urinary metabolite classifier that estimates MPA exposure. An independent cohort was used to test pharmacodynamic validity for allograft inflammation (urinary CXCL10 levels) and eGFR ratio (12mo/1mo eGFR) at 1 year. Results: Fifty‐two urine samples from separate children (36.5% female, 12.0 ± 5.3 years at transplant) were evaluated at 1.6 ± 2.5 years post‐transplant. Using all detected metabolites (n = 90), the classifier exhibited strong association with MPA AUC by principal component regression (r = 0.56, p <.001) and PLS (r = 0.75, p <.001). A practical classifier (top 10 metabolites; r = 0.64, p <.001) retained similar accuracy after cross‐validation (LOOCV; r = 0.52, p <.001). When applied to an independent cohort (n = 97 patients, 1053 samples), estimated mean MPA exposure over Year 1 was inversely associated with mean urinary CXCL10:Cr (r = −0.28, 95% CI −0.45, −0.08) and exhibited a trend for association with eGFR ratio (r = 0.35, p =.07), over the same time period. Conclusions: This urinary metabolite classifier can estimate MPA exposure and correlates with allograft inflammation. Future studies with larger samples are required to validate and evaluate its clinical application. [ABSTRACT FROM AUTHOR]

Background Monocyte chemotactic protein-1 (MCP-1) plays a direct role in the infiltration of macrophages and monocytes during the early stages of Henoch-Schonlein purpura (HSP) nephritis. The aim of this study was to compare the urinary MCP-1/creatinine levels in children with and without HSP nephritis and determine if they are associated with the severity of renal lesions. Methods We included 77 patients with HSP and 25 healthy control children. Levels of serum creatinine, urinalysis, and 12-h proteinuria assessments were performed. Urinary MCP-1 levels were determined by ELISA. Results Fifty-seven patients had nephritis (74%). Urinary MCP-1/creatinine levels were significantly higher in patients with HSP nephritis (median, 653 pg/mg) compared to those with HSP without nephritis (median, 269 pg/mg) or healthy children (191 pg/mg). In addition, higher MCP-1/creatinine levels were observed in HSP patients who had renal biopsy (median, 1,412 pg/mg) in comparison to HSP patients without renal biopsy (median, 302 pg/mg). The urinary MCP-1 cut-off value of 530 pg/mg could be used to distinguish patients who undergo renal biopsy with a sensitivity of 81% and specificity of 77%. Conclusions Urinary MCP-1/creatinine levels are elevated in the early stages of severe HSP nephritis and can be used as a biomarker for HSP nephritis. Keywords Henoch-Schonlein purpura nephritis * Macrophage * Proteinuria * Biomarkers * Glomerulonephritis, Introduction Henoch-Schonlein purpura (HSP) is the most frequent type of vasculitis observed in children [1, 2]. Immunoglobulin A (IgA) is known to play a fundamental role in the pathogenesis of [...]

Accurate assessment of renal function is critical for appropriate drug dosing of renally excreted compounds. Glomerular filtration rate (GFR) is considered the best marker of kidney function. Inulin clearance forms the gold standard for measuring GFR, both in adults and in children. The method is invasive, cumbersome, and smaller children require urinary catheterization for accurate timed urine collections. Nuclear medicine methods replaced inulin clearance in the 1970s after [sup.51]Cr EDTA clearance was introduced. Inulin has no plasma protein binding, whereas all commonly used radioisotopes have a small amount of plasma protein binding that leads to lower values. Only iohexol does not have significant plasma protein binding. The underestimation due to plasma protein binding is partially offset by overestimation due to the use of non-compartmental pharmacokinetic modeling of the plasma disappearance of the radioisotope. The problem could be overcome with a urinary nuclear medicine clearance method, but these have not been validated in children. Endogenous markers of GFR include serum creatinine and low molecular weight proteins such as cystatin C and beta-trace protein. Of these, estimation of GFR using cystatin C appears to be the most promising, although its accuracy in pregnancy and in the neonatal period may be limited. Keywords Inulin * Nuclear medicine * Cystatin C * eGFR * Creatinine * Chronic kidney disease, Introduction Adequate measurement of kidney function is important for the management of all children and adolescents. In the neonatal period, there is considerable ontogeny of drug disposition, largely due to [...]

Abstract: Components of whole blood and plasma are highly altered during the presentation of nephrotic syndrome. The present study was aimed to explore the influence of nephrotic syndrome on the [...]

The aim of this text is to resume the importance of the exercise of democratic social control of public policies, problematizing its reach in a capitalist, authoritarian and conservative state, to stimulate participatory processes within the social policies, which simultaneously strive for the expansion of social rights from an emancipatory point of view and broaden the collective consciousness and popular organization. First, we present a vision of public policies in the current context, then the challenges for the exercise of democratic social control, ending with the indication of some strategic possibilities for its implementation. [ABSTRACT FROM AUTHOR]