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BackgroundPrimary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial.MethodsFrom 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (

Background Pediatric patients with advanced chronic kidney disease (CKD) are often prescribed oral phosphate binders (PBs) for the management of hyperphosphatemia. However, available PBs have limitations, including unfavorable tolerability and safety. Methods This phase 3, multicenter, randomized, open-label study investigated safety and efficacy of sucroferric oxyhydroxide (SFOH) in pediatric and adolescent subjects with CKD and hyperphosphatemia. Subjects were randomized to SFOH or calcium acetate (CaAc) for a 10-week dose titration (stage 1), followed by a 24-week safety extension (stage 2). Primary efficacy endpoint was change in serum phosphorus from baseline to the end of stage 1 in the SFOH group. Safety endpoints included treatment-emergent adverse events (TEAEs). Results Eighty-five subjects (2-18 years) were randomized and treated (SFOH, n = 66; CaAc, n = 19). Serum phosphorus reduction from baseline to the end of stage 1 in the overall SFOH group (least squares [LS] mean ± standard error [SE]) was - 0.488 ± 0.186 mg/dL; p = 0.011 (post hoc analysis). Significant reductions in serum phosphorus were observed in subjects aged [greater than or equal to] 12 to [less than or equal to] 18 years (LS mean ± SE - 0.460 ± 0.195 mg/dL; p = 0.024) and subjects with serum phosphorus above age-related normal ranges at baseline (LS mean ± SE - 0.942 ± 0.246 mg/dL; p = 0.005). Similar proportions of subjects reported [greater than or equal to] 1 TEAE in the SFOH (75.8%) and CaAc (73.7%) groups. Withdrawal due to TEAEs was more common with CaAc (31.6%) than with SFOH (18.2%). Conclusions SFOH effectively managed serum phosphorus in pediatric patients with a low pill burden and a safety profile consistent with that reported in adult patients., Author(s): Larry A. Greenbaum [sup.1] , Nikola Jeck [sup.2] , Günter Klaus [sup.2] , Marc Fila [sup.3] , Cristina Stoica [sup.4] , Sahar Fathallah-Shaykh [sup.5] , Ana Paredes [sup.6] , [...]

The rate of twin births has increased by nearly 80% in recent decades largely due to advanced reproductive technologies. Twins are often born preterm and/or growth restricted which are independently associated with impaired renal and vascular development. Many preterm and twin infants are surviving into adulthood, albeit with an increased burden of chronic health conditions. Twinning as a research tool offers the unique opportunity to investigate the impact of genetics versus the environment on clinical outcomes. This educational review will focus on delineating our current understanding of the renal and cardiovascular development and long-term outcomes among twin born individuals. Specifically, existing literature regarding how twins differ in kidney size and function as well as vascular stiffness and hypertension profiles from singletons will be discussed. The unique situation of twin-twin transfusion syndrome which is associated with distinct short- and long-term cardio-renal disease will be highlighted. Ultimately, the ability to stratify risk of future cardio-renal disease at birth for infants born preterm and/or growth restricted, including twins, is important to guide clinical follow up. In addition, this early risk stratification could direct research efforts to better understand the mechanisms driving impaired organogenesis and allow for discovery of therapeutic interventions aimed at modifying disease progression and improving longevity in the most vulnerable infant subgroups., Author(s): Marissa J. DeFreitas [sup.1] , Carolyn L. Abitbol [sup.1] Author Affiliations: (1) Division of Pediatric Nephrology, University of Miami/Holtz Children's Hospital, , P.O. Box 016960 (M714), 33130, Miami, FL, [...]

Renal imaging is widely used in the assessment of surrogate markers of nephron mass correlated to renal function. Autopsy studies have tested the validity of various imaging modalities in accurately estimating 'true' nephron mass. However, in vivo assessment of nephron mass has been largely limited to kidney volume determination by ultrasonography (US) in pediatric populations. Practical limitations and risks create challenges in incorporating more precise 3D volumetric imaging, like magnetic resonance imaging (MRI), and computed tomography (CT) technologies, compared to US for routine kidney volume assessment in children. Additionally, accounting for structural anomalies such as hydronephrosis when estimating renal parenchymal area in congenital anomalies of the kidney and urinary tract (CAKUT) is important, as it correlates with chronic kidney disease (CKD) progression. 3D imaging using CT and MRI has been shown to be superior to US, which has traditionally relied on 2D measurements to estimate kidney volume using the ellipsoid calculation. Recent innovations using 3D and contrast-enhanced US (CEUS) provide improved accuracy with low risk. Indexing kidney volume to body surface area in children is an important standard that may allow early detection of CKD progression in high-risk populations. This review highlights current understanding of various imaging modalities in assessing nephron mass, discusses applications and limitations, and describes recent advances in the field of imaging and kidney disease. Although renal imaging has been a long-standing, essential tool in assessing kidney disease, innovation and new applications of established technologies provide important tools in the study and management of kidney disease in children., Author(s): Marissa J. DeFreitas [sup.1] , Chryso P. Katsoufis [sup.1] , Juan C. Infante [sup.2] , Michael L. Granda [sup.3] , Carolyn L. Abitbol [sup.1] , Alessia Fornoni [sup.4] Author [...]

Objective This study aimed to examine the association between maternal hypertension (HTN) exposure and neonatal acute kidney injury (AKI). Study Design Retrospective cohort study of 2,162 neonates admitted to 24 neonatal intensive care units (NICUs). Neonates were classified into the following exposure groups: any maternal HTN, chronic maternal HTN, preeclampsia/eclampsia, both, or neither. Demographics, clinical characteristics, and AKI status were compared using Chi-square and analysis of variance. General estimating logistic regression was used to estimate adjusted odds ratios and included a stratified analysis for site of delivery. Result Neonates exposed to any maternal HTN disorder had a tendency toward less overall and early AKI. When stratified by inborn versus outborn, exposure to both maternal HTN disorders was associated with a significantly reduced odds of early AKI only in the inborn neonates. Conclusion Exposure to maternal HTN, especially preeclampsia/eclampsia superimposed on chronic HTN, was associated with less likelihood of early AKI in the inborn group. Key Points Maternal HTN is associated with less neonatal AKI. Maternal HTN category is variably associated with AKI. Inborn status is an important contributor to this association. [ABSTRACT FROM AUTHOR]

Background: High-frequency ventilation (HFV) is frequently used in critically ill preterm neonates. We aimed to determine the incidence of acute kidney injury (AKI) in neonates less than 29 weeks gestation who received HFV in the first week of life and to determine if the rates of AKI differed in those who received other forms of respiratory support. Methods: This retrospective cohort study of 24 international, level III/IV neonatal intensive care units (NICUs) included neonates less than 29 weeks gestation from the AWAKEN study database. Exclusion criteria included the following: no intravenous fluids ≥ 48 h, admission ≥ 14 days of life, congenital heart disease requiring surgical repair at < 7 days of life, lethal chromosomal anomaly, death within 48 h, severe congenital kidney abnormalities, inability to determine AKI status, insufficient data on ventilation, and when the diagnosis of early AKI was unable to be made. Subjects were grouped into three groups based on ventilation modes (CPAP/no ventilation, conventional ventilation, and HFV). Results: The incidence of AKI was highest in the CPAP/no ventilation group, followed by HFV, followed by conventional ventilation (CPAP/no ventilation 48.5% vs. HFV 42.6% vs. conventional ventilation 28.4% (p = 0.009). An increased risk for AKI was found for those on HFV compared to CPAP/no ventilation (HR = 2.65; 95% CI:1.22–5.73). Conclusions: HFV is associated with AKI in the first week of life. Neonates on HFV should be screened for AKI. The reasons for this association are not clear. Further studies should evaluate the relationship between ventilator strategies and AKI in premature neonates. [ABSTRACT FROM AUTHOR]

The complex pathophysiology of progressive chronic kidney disease (CKD) and the development of mineral and bone disorder, abbreviated as CKD-MBD, is of vital importance to a pediatric patient. Paricalcitol, the 19 nor-1,25(OH).sub.2D.sub.2 analogue was shown to be effective and safe in the treatment of secondary hyperparathyroidism (SHPT) in adults almost two decades ago. It also significantly improved survival in dialysis patients compared to the standard calcitriol. The successful treatment of CKD-MBD in children is essential if they are to grow and survive into adulthood. It can be argued that it is more important for children with CKD than adults since they have early and prolonged disease risk exposure. In this issue of Pediatric Nephrology, Webb et.al. report a dual trial of the safety, efficacy, and pharmacokinetics of paricalcitol in children aged 10-16 years with moderate but significant efficacy in meeting the endpoint of >30% decrease in parathyroid hormone (PTH) levels from baseline with minimal adverse events. Much more research needs to be done to expand and develop clinical pharmaceutical trials in the use of paricalcitol in children, especially in the younger age categories. This current study has done much to open the doors for future studies, with the caveat that it has been long coming and much more needs to be done to compensate for this delay in the treatment of children with CKD-MBD and cardiovascular and renal disease progression., Author(s): Michael Freundlich [sup.1] , Carolyn L. Abitbol [sup.1] Author Affiliations: (1) 0000 0004 1936 8606grid.26790.3aDivision of Pediatric Nephrology, University of Miami Miller School of Medicine, P.O. Box 016960 (M714), [...]

This educational review will highlight the historical and contemporary references that establish a basic understanding of measurements of kidney function in the neonate and its relevance for the life of an individual. Importantly, the differential renal function of preterm infants relative to term infants has become paramount with the increased viability of preterm infants and the realization that kidney function is associated with gestational age. Moreover, neonatal kidney function is primarily associated with absolute renal mass and hemodynamic stability. Neonatal kidney function and its early developmental progression predict lifelong cardiovascular and renal disease risks. Validation of estimation equations of kidney function in this population has provided important reference data for other investigations and a clinical basis for prospective and longitudinal follow-up. Future research should be directed towards a better understanding of surrogate markers of kidney function from infancy through adulthood. Pediatric nephrologists should be aware of the developmental aspects of kidney function including the importance of the congenital nephron endowment and the preservation of kidney function throughout a lifetime. Key summary points * Nephrogenesis occurs in utero in concert with other organ systems by branching morphogenesis, including the lungs, pancreas, and vascular tree, with over 60 % of nephrons being formed during the last trimester. * Infants born preterm before 36 weeks' gestation are in active nephrogenesis and are at increased risk of having a decreased nephron endowment from prenatal and postnatal genetic and epigenetic hazards that will impact the patient for a lifetime. * Post-natal adaptation of kidney function is directly proportional to the number of perfused nephrons, estimated by total kidney volume (TKV), mean arterial pressure (MAP), and gestational age. * Accurate measurement of glomerular filtration rate (GFR) in infants is problematic due to the unavailability of the gold standard inulin. The traditional use of creatinine to estimate GFR is unreliable in preterm infants due to its tubular reabsorption by immature kidneys and its dependence on muscle mass as an endogenous marker. Alternative endogenous markers to estimate GFR are cystatin C and beta trace protein (BTP). * Long-term follow-up of renal function in those born preterm should be life long and should include assessment of GFR, total kidney volume (TKV) relative to body surface area (BSA), and cardiovascular risks including hypertension and vascular stiffness., Author(s): Carolyn L. Abitbol[sup.1] , Marissa J. DeFreitas[sup.1] , Jose Strauss[sup.2] Author Affiliations: (1) Division of Pediatric Nephrology, University of Miami/ Holtz Children's Hospital, Miami, FLUSA (2) Division of Pediatric [...]

Background Urinary biomarkers may be indicators of acute kidney injury (AKI), although little is known of their developmental characteristics in healthy neonates across a full range of gestational age (GA). The purpose of this study was to examine patterns of urinary biomarkers across GA groups from birth to 3 months of age. Methods Fifty-two infants ranging from 24 to 41 weeks' GA had urine assayed from birth through 3 months of age for 7 biomarkers including albumin (ALB), beta-2-microglobulin (B2M), cystatin-C (CysC), epidermal growth factor (EGF), neutrophil-gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin (UMOD). Results Of the seven urinary biomarkers, EGF and UMOD increased while others decreased with advancing GA. By 3 months of age, EGF and UMOD had increased in preterm infants to levels similar to those of term infants. UMOD/ml and EGF/ml appeared to be predominantly developmental biomarkers distinguishing estimated glomerular filtration rate (GFR) Conclusions Among healthy neonates, urinary biomarkers vary with GA. These data support the use of urinary biomarkers in the assessment of normal kidney development in the absence of injury., Author(s): Marissa J. DeFreitas[sup.1] , Wacharee Seeherunvong[sup.1] , Chryso P. Katsoufis[sup.1] , Satish RamachandraRao[sup.2] , Shahnaz Duara[sup.3] , Salih Yasin[sup.4] , Gaston Zilleruelo[sup.1] , Maria M. Rodriguez[sup.5] , Carolyn L. [...]

Background As 1,25(OH).sub.2D.sub.3 vitamin D3 induces fibroblast growth factor-23 (FGF-23) production and suppresses the renin-angiotensin-aldosterone system (RAAS), its absence in vitamin-D-dependent rickets type I (VDDR-I) may have adverse health consequences. Case description An infant presented at age 8 months with hypocalcemia and rickets and very low 1,25(OH).sub.2D.sub.3 levels. Genetic analysis confirmed VDRR-I, and calcitriol therapy was initiated. During periods of nonadherence to therapy, chemical measurements revealed detectable FGF-23 levels, with undetectable 1,25(OH).sub.2D.sub.3, hypophosphatemia, low tubular reabsorption of phosphate, hypocalcemia, and very elevated parathyroid hormone (PTH) levels. These changes, in addition to elevated RAAS levels, normalized during calcitriol therapy despite elevated FGF-23 levels. At age 12 years, all rachitic manifestations were absent, and bone mineral density (BMD) and the echocardiogram were normal. Conclusions Whereas 1,25(OH).sub.2D.sub.3 is not indispensable for FGF-23 production, PTH in the absence of vitamin D may maintain FGF-23 secretion despite hypocalcemia. Normalization of urinary phosphate losses despite elevated FGF-23 during calcitriol-mediated suppression of secondary hyperparathyroidism points to a cardinal role of PTH as a cause of the phosphaturia in VDRR-I. Normalization of RAAS by calcitriol may conceivably prevent adverse cardiovascular outcomes., Author(s): Carlos Cuervo[sup.1] , Carolyn L. Abitbol[sup.1] , Gaston E. Zilleruelo[sup.1] , Michael Freundlich[sup.1] Author Affiliations: (1) Division of Pediatric Nephrology, University of Miami Miller School of Medicine, PO Box [...]

Background Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/ adolescents mature into young adults. The identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications. Methods Data collected from HIV-infected youth followed for ≥ 48 months were analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. Results Of the 1,874 at-risk children enrolled in the study, 428 (23 %) developed RLE, which persisted in 229 of these (54 %). CD4 percentages of < 25 % [hazard ratio (HR) 0.63, p < 0.002) and an HIV viral load of > 100,000 copies/ml (HR 0.31, p < 0.01) were associated with reduced rates of resolution, while in most cases exposure to highly active antiretroviral therapy (HAART)/nephrotoxic HAART prior to or subsequent to RLE were not. Persistence of RLE was 88 % sensitive for identifying new RD. Negative predictive values for RD were > 95 % for both the at-risk cohort and those with RLE. Conclusions Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD. Keywords HIV * HIV renal disease * HAART * Pediatric * Perinatal, Introduction Renal disease in human immunodeficiency virus (HIV) type 1 (HIV-1)-infected children and adolescents may occur as a result of the complications of HIV-1 infection and as well as from [...]