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Background: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. Methods: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy. Results: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes. Conclusions: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs. [ABSTRACT FROM AUTHOR]

Background: Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity. Methods: A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups. Results: Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI. Conclusions: AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome relapse within 6 months is a known risk factor for steroid-dependent nephrotic syndrome/frequently relapsing nephrotic syndrome (SDNS/FRNS), but the risk of early development of SDNS/FRNS and initiation of immunosuppression therapy remains unknown. Methods: Patients with childhood-onset idiopathic nephrotic syndrome who had the first relapse within 6 months were enrolled. We analyzed the relationship between the time of the first relapse or the time of initial remission and incidence of SDNS/FRNS or initiation of immunosuppression therapy. Results: Forty-five patients were enrolled. Twenty out of 23 patients (87%) with the first relapse within 30 days after discontinuing initial steroid therapy experienced a second relapse within 30 days after discontinuing steroid therapy. Additionally, most patients in this group (96%) experienced a second relapse within 6 months after the onset and were diagnosed as SDNS/FRNS at this time. In this group, the incidence of SDNS/FRNS development within 6 months was 96%. In contrast, the incidence of SDNS/FRNS development within 6 months was 18% in patients with the first relapse more than 30 days after steroid discontinuation. The incidence of initiation of immunosuppressive agents within 6 months was 83% in the former group and 14% in the latter group. Conclusions: Most patients with the first relapse within 30 days after discontinuing steroid therapy developed SDNS/FRNS and were administered immunosuppressive agents within 6 months. Thus, it might be reasonable to start immunosuppression therapy in this group without waiting for the second relapse. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) in infants is a common, potentially life-threatening bacterial infection, and must be managed carefully through the entire chain of care from diagnosis, choice of treatment, follow-up and risk stratification of future complications. This Swedish nationwide study of infant UTI was conducted to evaluate the current management of infant UTI, yield of investigations and the Swedish UTI guidelines' ability to detect abnormalities of importance in the urinary tract. Methods: Infants < 1 year with a first episode of UTI were included in a prospective multicenter study. Treatment and follow-up were provided by local pediatricians. Clinical and laboratory findings and imaging results were reported to the coordinating center. The current management and results were compared with a previous Swedish study. Results: One thousand three hundred six infants were included. Urine sampling was performed with clean catch technique in 93% of patients. Initial oral antibiotic treatment was used in 63%, predominantly third generation cephalosporines. Permanent kidney abnormalities were found in 10% and dilating vesicoureteral reflux (VUR) in 8%. Higher rates of male gender, non-E. coli infection and ultrasound dilatation were seen in infants < 1 month. UTI recurrences were reported in 18%. Conclusions: Infant UTI is still generating a considerable amount of follow-up examinations. There is a significant shift towards clean catch as the main urine sampling method. Voiding cystourethrography is performed less frequently reducing the findings of low grade VUR. The incidence of renal scarring is comparable with earlier studies which suggests that the Swedish guidelines are able to identify individuals with risk for long-term complications. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: Augmented renal clearance (ARC) holds a risk of subtherapeutic drug concentrations. Knowledge of patient-, disease-, and therapy-related factors associated with ARC would allow predicting which patients would benefit from intensified dosing regimens. This study aimed to identify ARC predictors and to describe ARC time-course in critically ill children, using iohexol plasma clearance (CLiohexol) to measure glomerular filtration rate (GFR). Methods: This is a retrospective analysis of data from the "IOHEXOL" study which validated GFR estimating formulas (eGFR) against CLiohexol. Critically ill children with normal serum creatinine were included, and CLiohexol was performed as soon as possible after pediatric intensive care unit (PICU) admission (CLiohexol1) and repeated (CLiohexol2) after 48–72 h whenever possible. ARC was defined as CLiohexol exceeding normal GFR for age plus two standard deviations. Results: Eighty-five patients were included; 57% were postoperative patients. Median CLiohexol1 was 122 mL/min/1.73 m2 (IQR 75–152). Forty patients (47%) expressed ARC on CLiohexol1. Major surgery other than cardiac surgery and eGFR were found as independent predictors of ARC. An eGFR cut-off value of 99 mL/min/1.73 m2 and 140 mL/min/1.73 m2 was suggested to identify ARC in children under and above 2 years, respectively. ARC showed a tendency to persist on CLiohexol2. Conclusions: Our findings raise PICU clinician awareness about increased risk for ARC after major surgery and in patients with eGFR above age-specific thresholds. This knowledge enables identification of patients with an ARC risk profile who would potentially benefit from a dose increase at initiation of treatment to avoid underexposure. Trial registration: ClinicalTrials.gov NCT05179564, registered retrospectively on January 5, 2022. [ABSTRACT FROM AUTHOR]

Background: Continuous-flow ventricular assist devices (CF-VADs) are used increasingly in pediatric end-stage heart failure (ESHF) patients. Alongside common risk factors like oxidant injury from hemolysis, non-pulsatile flow constitutes a unique circulatory stress on kidneys. Post-implantation recovery after acute kidney injury (AKI) is commonly reported, but long-term kidney outcomes or factors implicated in the evolution of chronic kidney disease (CKD) with prolonged CF-VAD support are unknown. Methods: We studied ESHF patients supported > 90 days on CF-VAD from 2008 to 2018. The primary outcome was CKD (per Kidney Disease Improving Global Outcomes (KDIGO) criteria). Secondary outcomes included AKI incidence post-implantation and CKD evolution in the 6–12 months of CF-VAD support. Results: We enrolled 134 patients; 84/134 (63%) were male, median age was 13 [IQR 9.9, 15.9] years, 72/134 (54%) had preexisting CKD at implantation, and 85/134 (63%) had AKI. At 3 months, of the 91/134 (68%) still on a CF-VAD, 34/91 (37%) never had CKD, 13/91 (14%) developed de novo CKD, while CKD persisted or worsened in 49% (44/91). Etiology of heart failure, extracorporeal membrane oxygenation use, duration of CF-VAD, AKI history, and kidney replacement therapy were not associated with different CKD outcomes. Mortality was higher in those with AKI or preexisting CKD. Conclusions: In the first multicenter study to focus on kidney outcomes for pediatric long-term CF-VAD patients, preimplantation CKD and peri-implantation AKI were common. Both de novo CKD and worsening CKD can happen on prolonged CF-VAD support. Proactive kidney function monitoring and targeted follow-up are important to optimize outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: We validated the prevalence of albuminuria and its association with kidney function and hemodynamics in pre-school children who underwent surgery for congenital heart disease (CHD). Methods: From 403 patients who had undergone surgery for CHD at least 6 months before pre-school and were admitted to our hospital between 2011 and 2015, 75 who underwent blood and urine tests and cardiac catheterization were included in this study. The urinary albumin-to-creatinine ratio (ACR) was quantified, and the relationship of ACR with physical and laboratory findings and hemodynamics assessed using cardiac catheterization was analyzed. Results: The study cohort was divided into three groups: Fontan group (n = 25), tetralogy of Fallot (TOF) group (n = 18), and control group (other biventricular CHDs; n = 32). The median age of patients was 5.9 years. ACR was higher in the Fontan group than in the TOF and control groups (median: 15.0 vs. 5.0 and 0.0 mg/g, p < 0.001). Moreover, albuminuria (ACR > 30 mg/g) was observed in 20.0% of Fontan patients, while ACR was associated with potential complicating factors of Fontan circulation: high central venous pressure, high mean pulmonary artery pressure, and worse than moderate atrioventricular regurgitation. ACR showed a moderate correlation with the cystatin C-based estimated glomerular filtration rate (r = − 0.725, p < 0.001). Conclusions: Measurement of albuminuria in Fontan patients before they join elementary school is useful because it reflects kidney function and hemodynamic factors that can worsen their condition. Identification and management of patients with albuminuria may facilitate early therapeutic intervention for worsening Fontan factors, eventually delaying the deterioration of kidney function. [ABSTRACT FROM AUTHOR]

Background: To determine if the implementation of a posterior urethral valves (PUV) clinic and standardized management pathway improves the short-term kidney outcomes of infants with PUV. Methods: From 2016–2022, 50 consecutive patients were divided into groups after the implementation of the clinic (APUV, n = 29) and before (BPUV, n = 21) during a comparable timeframe. Assessed data included age at initial visit, timing and type of surgery, frequency of follow-up visits, medications, nadir creatinine, and development of CKD/kidney failure. Data are shown as median with interquartile range (IQR) and odds ratios (OR) with 95% confidence interval (CI). Results: APUV had higher rates of prenatal diagnoses (12/29 vs. 1/21; p = 0.0037), earlier initial surgical intervention (8 days; IQR 0, 105 vs. 33 days; IQR 4, 603; p < 0.0001), and higher rates of primary diversions (10/29 vs. 0/21; p = 0.0028). Standardized management led to earlier initiation of alpha blockers (326 days; IQR 6, 860 vs. 991; IQR 149, 1634; p = 0.0019) and anticholinergics (57 days; IQR 3, 860 vs. 1283 days; IQR 477, 1718; p < 0.0001). Nadir creatinine was reached at earlier ages in APUV (105 days; IQR 2, 303 vs. 164 days; IQR 21, 447; p = 0.0192 BPUV). One patient progressed to CKD5 in APUV compared to CKD3, CKD5 and one transplant in BPUV. Conclusion: Implementing the PUV clinic with standardized treatment expedited postnatal management and resulted in a higher number of cases detected prenatally, a shift in primary treatment, younger ages at initial treatment, reduced time to nadir creatinine, and timely initiation of supportive medications. [ABSTRACT FROM AUTHOR]

Background : Patients on peritoneal dialysis (PD) may develop PD-related complications that necessitate abdominal surgery. However, when to resume PD and how to prescribe PD fluid after surgery in pediatric patients are unknown. Methods: Patients on PD who underwent small-incision abdominal surgery between May 2006 and October 2021 were included in this retrospective observational study. The complications after surgery and characteristics of patients with PD fluid leakage were analyzed. Results: Thirty-four patients were included. They underwent 45 surgical procedures, including 23 inguinal hernia repairs, 17 PD catheter repositioning or omentectomy, and 5 others. The median time to resume PD was 1.0 (IQR, 1.0–3.0) days, and the median PD exchange volume at the initiation of PD after surgery was 25 (IQR, 20–30) ml/kg/cycle. PD-related peritonitis occurred in two patients after omentectomy and one after inguinal hernia repair. There was no PD fluid leakage or hernia recurrence among the 22 patients who had a hernia repair. Peritoneal leakage occurred in 3 of the 17 patients who had PD catheter repositioning or an omentectomy and was treated conservatively. No patients who resumed PD 3 days after small-incision abdominal surgery with less than half of PD volume had fluid leakage. Conclusions: Our findings demonstrated that PD could be resumed within 48 h of inguinal hernia repair with no PD fluid leakage or hernia recurrence in pediatric patients. In addition, resuming PD 3 days after a laparoscopic procedure with less than half of the usual dialysate volume might reduce the risk of PD fluid leakage. [ABSTRACT FROM AUTHOR]

Background: Continuous kidney replacement therapy (CKRT) has been expanded from simple kidney replacement therapy to the field of critical illness in children. However, CKRT is rarely used in critically ill neonates in the neonatal intensive care unit (NICU). This study aimed to describe patients' clinical characteristics at admission and CKRT initiation, CKRT effects, short-term outcomes, and predictors of death in critically ill neonates. Methods: A 7-year single-center retrospective study in a tertiary NICU. Results: Thirty-nine critically ill neonates received CKRT between May 2015 and April 2022 with a mortality rate of 35.9%. The most common primary diagnosis was neonatal sepsis in 15 cases (38.5%). Continuous veno-venous hemodiafiltration and continuous veno-venous hemofiltration were applied in 43.6% and 56.4% of neonates, respectively. The duration of CKRT was 44 (18, 72) h. Thirty-one patients (79.5%) had complications due to CKRT-related adverse events, and the most common complication was thrombocytopenia. Approximately 12 h after the CKRT initiation, urine volume, mean arterial pressure, and pH were increased, and serum creatinine, blood urea nitrogen, and blood lactate were decreased. In the multivariate logistic regression analysis, neonatal critical illness score [odds ratio 0.886 (0.786 ~ 0.998), P = 0.046] was an independent risk factor for death in critically ill neonates who received CKRT. Conclusions: CKRT can be an effective and feasible technique in critically ill neonates, but the overall mortality and CKRT-related complications are relatively high. Furthermore, the probability of death is greater among neonates with greater severity of illness at CKRT initiation. [ABSTRACT FROM AUTHOR]

Background : This study aimed to determine incidence of kidney complications in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients. Methods: Pediatric allogeneic HSCT patients were included. Post-transplantation urinary system complications were collected from medical records and glomerular filtration rates at last visit compared with clinical parameters. Additionally, 24-h ambulatory blood pressure monitoring was performed. Results: The study included 165 pediatric patients. Acute kidney injury (AKI) developed in 125 (75.8%) patients of whom 54 (43.2%) had stage 1, 36 (28.8%) stage 2, and 35 (28%) stage 3 AKI. Primary malignant disease and viral infection post-HSCT were associated with increased risk of AKI (OR: 4; 95%CI: 1.2–13, p = 0.022 and OR: 2.9; 95%CI: 1.2–6.8, p = 0.014, respectively). Mean duration of post-HSCT follow-up was 4.4 ± 2.5 years, during which time 8 patients had chronic kidney disease (CKD) (stage 1, 4 patients; stage 2, 3 patients; stage 3, 1 patient). CKD incidence was higher in patients in whom stem cell product was bone marrow + cord blood and mobilized peripheral blood, compared to bone marrow alone (40–37.5% versus 5.1%, p = 0.002). Based on 24-h ABPM, 14.7% and 7.4% of patients with normal office blood pressure had pre-hypertension and hypertension, respectively. In patients with albuminuria/severe albuminuria, daytime and nighttime systolic SDS scores were higher than those without albuminuria/severe albuminuria (p = 0.010 and p = 0.004, respectively). Conclusions: Incidence of AKI is higher in pediatric HSCT patients with primary malignant disease and those with documented viral infection. Our study highlights the beneficial role of 24-h ABPM as a routine part of standard care of pediatric HSCT recipients. [ABSTRACT FROM AUTHOR]

Background: Both IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephropathy (HSPN) are characterized by glomerular mesangial IgA deposition. Several large studies on adults have suggested that glomerular C4d deposition has prognostic value in IgAN. However, there are few relevant studies on the clinical value of C4d deposition in children with IgAN or HSPN. Methods: We performed a retrospective cohort study in pediatric patients with IgAN or HSPN. Clinicopathological data were collected at the time of kidney biopsy. Kidney C4d deposition was analyzed by immunohistochemistry. The end point was defined as a ≥ 20% decrease in estimated glomerular filtration from baseline. Results: We enrolled 75 children, including 36 children with IgAN and 39 with HSPN. The prevalence of C4d deposition was 36% (27/75). C4d deposition was more abundant in children with proteinuria ≥ 50 mg/kg/day (51.9% versus 20.8%, P = 0.006) or nephrotic syndrome (37.0% versus 10.4%, P = 0.006). Mesangial hypercellularity (hazard ratio [HR], 5.745, 95% confidence interval [CI], 1.670–19.761, P = 0.006) and IgM deposition (HR, 4.522, 95% CI, 1.321–15.478, P = 0.016) were associated with C4d deposition. After a median follow-up of 22 months, seven (19.4%) IgAN patients and one (2.6%) HSPN patient had decreased kidney function. In children with IgAN, positive C4d was associated with decreased kidney function (P = 0.047). Conclusion: Glomerular C4d deposition was associated with mesangial hypercellularity and glomerular IgM deposition in IgAN and HSPN. Glomerular C4d deposition may be a risk factor for eGFR decline in children with IgAN. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: Peritonitis is a significant cause of morbidity and healthcare cost among pediatric patients undergoing peritoneal dialysis. Culture-negative peritonitis has been associated with an increased risk of technique failure. Known risk factors for culture-negative peritonitis are related to the process of collection and sample processing for culture, but additional studies are needed. A culture detection rate of 16.7% was identified among our patients undergoing peritoneal dialysis, which is below the national benchmark of ≥ 85%. Our primary objective of this quality improvement project was to improve culture detection rates. Methods: Interventions were developed aimed at standardizing the process of effluent collection and laboratory processing, timely collection and processing of samples, and addressing other modifying risk factors for lack of bacterial growth from culture. These interventions included direct inoculation of effluent into blood culture bottles at bedside and use of an automated blood culture system. Two Plan-Do-Study-Act cycles were completed prior to moving to the sustain phase. Results: The culture detection rate improved from 16.7% (pre-intervention) to 100% (post-intervention). A decrease in the median process time also occurred from 83 min (pre-intervention) to 53 min (post-intervention). An individual and moving range chart identified a decrease in both the centerline (mean) and upper control limit, indicating that the process became more reliable during the sustain phase. Conclusions: An improvement in process time and culture positivity rate occurred following standardization of our PD fluid culture process. Future studies should be aimed at the impact of the components of collection and processing methods on the effluent culture yield. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: IgA vasculitis (IgAV) is the most common type of vasculitis in children. There is a lack of consensus for management of significant IgAV nephritis (IgAVN). This study was designed to identify the most used treatment options and describe their efficacy. Methods: This is a multicenter retrospective study of children age 1–21 years with IgAVN who were managed for at least 6 months by a nephrologist. Subjects with at least microscopic hematuria and proteinuria and/or decreased kidney function were enrolled. Kidney outcome was assessed by eGFR and urine protein/creatinine (UPC) ratios at 2–4 weeks, 3, 6, and 12 months post-diagnosis. Results: A total of 128 subjects with median age of 7 years (range 2–18) were included. Of these, 69 subjects had kidney biopsy with crescents detected in 53%. AKI (P = 0.039), nephrosis (P = 0.038), and crescents on biopsy (P = 0.013) were more likely in older patients. Patients with UPC > 1 mg/mg were more likely to get a kidney biopsy (P < 0.001) and to be treated with steroids ± immunosuppressive (IS) agents (P = 0.001). Sixty-six percent of patients were treated with steroids and/or IS agents for variable durations. Anti-metabolite agents were the most common IS agents used with variability in dosing and duration. At 12 months, most subjects had a normal eGFR (79%) (median 123, range 68–207 mL/min/1.73 m2) and no proteinuria (median UPC 0.15, range 0.01–4.02 mg/mg). Conclusions: IS agents are frequently used in managing IgAVN associated with heavy proteinuria, nephrosis, and/or AKI. Prospective studies are needed to determine indications and needed duration of IS therapy. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: There is evidence of increased risk of hypertension, albuminuria, and development of chronic kidney disease (CKD) in long-term follow-up of survivors of Wilms tumor (WT). However, most studies were conducted in heterogeneous groups, including patients with solitary kidney. In addition, little is known about tubular dysfunction. This study aimed to investigate kidney sequelae, including CKD development, hypertension, and glomerular and tubular damage in WT survivors. Methods: This cross-sectional, single-center study included 61 patients treated for WT. Surrogates for kidney sequelae were defined as presence of at least one of the following: decrease in GFR for CKD, hypertension detected by ambulatory blood pressure monitoring, albuminuria (albumin-to-creatinine ratio [ACR] > 30 mg/g), or increase in at least one tubular biomarker (beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, kidney injury marker-1, and liver fatty acid-binding protein) in 24-h urine. Results: Median age of patients was 11.7 years, with median follow-up of 8.8 years. Thirty-eight patients (62%) had at least one surrogate for kidney sequelae. Twenty-four patients (39%) had CKD, 14 patients (23%) had albuminuria, 12 patients (21%) had hypertension, and 11 patients (18%) had tubular damage. Urine ACR was significantly higher in patients with advanced tumor stage and patients with nephrotoxic therapy than their counterparts (p < 0.05), but neither eGFR nor tubular biomarkers showed any association with tumor- or treatment-related factors. Conclusions: A considerable number of patients with WT have kidney sequelae, especially early-stage CKD with a high prevalence. Albuminuria emerges as a marker associated with tumor stages and nephrotoxic treatment. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: Cases of Henoch–Schönlein purpura nephritis (HSPN) with moderate severity were demonstrated to achieve good prognosis after treatment with renin-angiotensin system (RAS) inhibitors. However, some patients required additional treatment for recurrence after remission. This study aimed to clarify the effect of RAS inhibitors in HSPN cases with moderate severity, including the proportion of cases with recurrence and their response to additional treatment. Methods: Among 126 patients diagnosed with HSPN between 1996 and 2019, 71 patients with clinicopathologically diagnosed HSPN of moderate severity, defined as ISKDC grade II–IIIa and serum albumin ≥ 2.5 g/dL, were investigated. Results: Proteinuria became negative after RAS inhibitor treatment alone in all 71 cases. However, 16 (22.5%) had recurrence. Eleven recurrent cases achieved negative proteinuria again following additional treatment. At the last follow-up (median 46.5 months; IQR, 23.2–98.2), 5 patients had persistent mild proteinuria; no patients had estimated glomerular filtration rate < 90 mL/min/1.73 m2. The pathological findings in all recurrent cases were ISKDC grade IIIa. The 16 recurrent cases had significantly higher proportions of glomeruli with global/segmental sclerosis (25.0 vs. 0%, P < 0.001) and tubular atrophy/interstitial fibrosis (37.5 vs. 12.7%, P =0.0 24) than 55 cases without recurrence. Conclusions: Japanese childhood HSPN cases with moderate severity had good outcomes without need for corticosteroids or immunosuppressants, when prescribed RAS inhibitor treatment. Even in recurrent cases, abnormal proteinuria was transient, and prognosis was excellent. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: Urine sodium and potassium are used as surrogate markers for dietary consumption in adults with hypertension, but their role in youth with hypertension and their association with components of the renin-angiotensin-aldosterone system (RAAS) are incompletely characterized. Some individuals with hypertension may have an abnormal RAAS response to dietary sodium and potassium intake, though this is incompletely described. Our objective was to investigate if plasma renin activity and serum aldosterone are associated with urine sodium and potassium in youth referred for hypertensive disorders. Methods: This pilot study was a cross-sectional analysis of baseline data from 44 youth evaluated for hypertensive disorders in a Hypertension Clinic. We recorded urine sodium and potassium concentrations normalized to urine creatinine, plasma renin activity, and serum aldosterone and calculated the sodium/potassium (UNaK) and aldosterone/renin ratios. We used multivariable generalized linear models to estimate the associations of renin and aldosterone with urine sodium and potassium. Results: Our cohort was diverse (37% non-Hispanic Black, 14% Hispanic), 66% were male, and median age was 15.3 years; 77% had obesity and 9% had a secondary etiology. Aldosterone was associated inversely with urine sodium/creatinine (β: −0.34, 95% CI −0.62 to −0.06) and UNaK (β: −0.09, 95% CI −0.16 to −0.03), and adjusted for estimated glomerular filtration rate and serum potassium. Conclusions: Higher serum aldosterone levels, but not plasma renin activity, were associated with lower urine sodium/creatinine and UNaK at baseline in youth referred for hypertensive disorders. Further characterization of the RAAS could help define hypertension phenotypes and guide management. [ABSTRACT FROM AUTHOR]

Background: Children living with HIV frequently show high plasma levels of fibroblast growth factor-2 (FGF-2/bFGF). FGF-2 accelerates the progression of several experimental kidney diseases; however, the role of circulating FGF-2 in childhood HIV-chronic kidney diseases (HIV-CKDs) is unknown. We carried out this study to determine whether high plasma FGF-2 levels were associated with the development of HIV-CKDs in children. Methods: The plasma and urine FGF-2 levels were measured in 84 children (< 12 years of age) living with HIV during the pre-modern antiretroviral era, and followed for at least 3 years to determine the prevalence of proteinuria and HIV-CKDs. We also assessed the distribution of the kidney FGF-2 binding sites by autoradiography and Alcian blue staining, and explored potential mechanisms by which circulating FGF-2 may precipitate HIV-CKDs in cultured kidney epithelial and mononuclear cells derived from children with HIV-CKDs. Results: High plasma FGF-2 levels were associated with a high viral load. Thirteen children (~ 15%) developed HIV-CKDs and showed a large reservoir of FGF-2 low-affinity binding sites in the kidney, which can facilitate the recruitment of circulating FGF-2. Children with high plasma and urine FGF-2 levels had 73-fold increased odds (95% CI 9–791) of having HIV-CKDs relative to those with normal FGF-2 values. FGF-2 induced the proliferation and decreased the expression of APOL-1 mRNA in podocytes, and increased the attachment and survival of infected mononuclear cells cultured from children with HIV-CKDs. Conclusions: High plasma FGF-2 levels appear to be an additional risk factor for developing progressive childhood HIV-CKDs. [ABSTRACT FROM AUTHOR]

Objective: To determine how hypotension in the first 48 h of sepsis management impacts acute kidney injury (AKI) development and persistence. Study design: Retrospective study of patients > 1 month to < 20 years old with sepsis in a pediatric ICU between November 2012 and January 2015 (n = 217). All systolic blood pressure (SBP) data documented within 48 h after sepsis recognition were collected and converted to percentiles for age, sex, and height. Time below SBP percentiles and below pediatric advanced life support (PALS) targets was calculated by summing elapsed time under SBP thresholds during the first 48 h. The primary outcome was new or persistent AKI, defined as stage 2 or 3 AKI present between sepsis day 3–7 using Kidney Disease: Improving Global Outcomes creatinine definitions. Secondary outcomes included AKI-free days (days alive and free of AKI) and time to kidney recovery. Results: Fifty of 217 sepsis patients (23%) had new or persistent AKI. Patients with AKI spent a median of 35 min under the first SBP percentile, versus 4 min in those without AKI. After adjustment for potential confounders, the odds of AKI increased by 9% with each doubling of minutes spent under this threshold (p = 0.03). Time under the first SBP percentile was also associated with fewer AKI-free days (p = 0.02). Time spent under PALS targets was not associated with AKI. Conclusions: The duration of severe systolic hypotension in the first 48 h of pediatric sepsis management is associated with AKI incidence and duration when defined by age, sex, and height norms, but not by PALS definitions. [ABSTRACT FROM AUTHOR]

Background: Subjects with a congenital solitary kidney (CSK) are believed to be at risk of hypertension due to their low number of nephrons. However, as CSK is a congenital abnormality of the kidney or urinary tract (CAKUT), subtle dysplastic changes contributing to hypertension cannot be excluded. Methods: We retrospectively compared office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) between two groups of children with CAKUT, aged 6–18 years: Group A with a CSK and Group B with two kidneys. All had normal renal parenchyma on scintigraphy and normal renal function. OBP and mean systolic and diastolic 24-h, daytime and nighttime ambulatory BP records were analyzed. The distribution of OBP and APBM as continuous values and the prevalence of hypertension (ambulatory/severe ambulatory or masked hypertension) in the two groups were compared. Results: There were 81 patients in Group A and 45 in Group B. Median OBP standard deviation scores were normal in both groups, without significant differences. Median ABPM standard deviation scores, although normal, were significantly higher in Group A and the prevalence of hypertension was higher (ambulatory/severe ambulatory or masked) (33.3 vs. 13.3%, p = 0.019), mainly because of the greater occurrence of masked hypertension. Conclusions: Our data show that a CSK per se can be associated with an increased risk of hypertension from the pediatric age. Therefore, ABPM, which has proved valuable in the screening of hypertension, is warranted in children with a CSK, even if laboratory and imaging assessment is otherwise normal. [ABSTRACT FROM AUTHOR]

Background: Patients with refractory nephrotic syndrome (NS) are at high risk of medication-induced glucose metabolism disorders, because of their long-term use of diabetogenic medications, particularly glucocorticoids and calcineurin inhibitors (CNIs). However, there have been no comprehensive evaluations of glucose metabolism disorders in pediatric patients with refractory NS. Moreover, glucocorticoids and CNIs could not be discontinued in these patients until the effectiveness of rituximab on refractory NS was shown, and therefore, there has been limited opportunity to evaluate glucose metabolism disorders after discontinuation of these medications. Methods: Consecutive pediatric patients who started rituximab treatment for refractory NS were enrolled. Their glucose metabolism conditions were evaluated using the oral glucose tolerance tests (OGTT) and HbA1c levels at the initiation of rituximab treatment. Patients with glucose metabolism disorders at the first evaluation were reevaluated after approximately 2 years. Results: Overall, 57% (20/35) of study patients had glucose metabolism disorders, and 40% (8/20) of these patients were detected only by their 2-h OGTT blood glucose levels and not by their fasting blood glucose or HbA1c levels. Non-obese/non-overweight patients had significantly more glucose metabolism disorders than obese/overweight patients (p = 0.019). In addition, glucose metabolism disorders in 71% (10/14) of patients persisted after the discontinuation of glucocorticoids and CNIs. Conclusions: Whether the patient is obese/overweight or not, patients with refractory NS are at high risk of developing glucose metabolism disorders, even in childhood. Non-obese/non-overweight patients who are at high risk of diabetes need extra vigilance. [ABSTRACT FROM AUTHOR]

Introduction: Liver-kidney transplantation is a rare procedure in children, with just ten to 30 cases performed annually worldwide. The main indications are autosomal recessive polycystic liver-kidney disease and primary hyperoxaluria. This study aimed to report outcomes of liver-kidney transplantation in a cohort of pediatric patients. Methods: We retrospectively analyzed all pediatric liver-kidney transplantations performed in our center between September 2000 and August 2015. Patient data were obtained by reviewing inpatient and outpatient medical records and our transplant database. Results: A total of 14 liver-kidney transplants were performed during the study period, with a median patient age and weight at transplant of 144.4 months (131.0-147.7) and 27.3 kg (12.0-45.1), respectively. The indications for liver-kidney transplants were autosomal recessive polycystic liver-kidney disease (8/14), primary hyperoxaluria −1 (5/14), and idiopathic portal hypertension with end-stage renal disease (1/14). Median time on waiting list was 8.5 months (5.7-17.3). All but two liver-kidney transplants were performed simultaneously. Patients with primary hyperoxaluria-1 tended to present a delayed recovery of renal function compared with patients transplanted for other indications (62.5 vs 6.5 days, respectively, P 0.076). Patients with liver-kidney transplants tended to present a lower risk of acute kidney rejection than patients transplanted with an isolated kidney transplant (7.2% vs 32.7%, respectively; P < 0.07). Patient and graft survival at 1, 3, and 5 years were 100%, 91.7%, 91.7%, and 91.7%, 83.3%, 83.3%, respectively. No other grafts were lost. Conclusion: Long-term results of liver-kidney transplants in children are encouraging, being comparable with those obtained in isolated liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Rituximab (RTX) is increasingly being used in place of calcineurin inhibitors (CNI) in pediatric patients with steroid-dependent nephrotic syndrome (SDNS). However, despite its favorable safety profile, its unit cost is prohibitive. We therefore compared the healthcare costs associated with the use of both agents in a retrospective cohort. Methods: This study was a retrospective analysis of data retrieved from the medical charts and electronic databases of pediatric patients (age range 2-18 years) with SDNS who were treated with either CNI or RTX from January 2008 to December 2012 at Children's Hospital of New Orleans, Louisiana. The minimum follow-up period was 12 months. Results: Of the 18 patients whose medical data were analyzed, ten received RTX and eight were treated with CNI. The annualized healthcare cost for the rituximab group was $197,031 versus $189,857 (all values in US dollars) for the CNI group ( p > 0.05). At the 12-month follow-up, more patients in the RTX group were in remission (40 vs. 25%). Duration of freedom from steroid use was longer in the RTX group, while body mass index was higher in the CNI arm ( p > 0.05). No significant adverse events occurred in either group. Conclusion: The expenditure for the RTX and CNI groups was comparable, but there were fewer clinical encounters in the former group, potentially reducing the burden of healthcare on the patient's family. [ABSTRACT FROM AUTHOR]

Background: Increased plasma cell infiltration in renal allograft biopsies is a rare finding associated with poor outcome in adult renal transplant recipients. The clinical impact of increased plasma cell infiltrates in paediatric renal transplant recipients (pRTR) remains unknown. Methods: We conducted a retrospective case-control study from April 1996 to March 2014 comparing the outcome of pRTR with increased (>10 % of infiltrate) plasma cells in renal transplant biopsies to a control cohort of pRTR without increased plasma cell infiltration but similar grade of rejection according to Banff classification. Results: Increased plasma cell infiltrates were present in 14 of 162 (9 %) reviewed pRTR aged 3.2-17.5 (median 13.4) years at time of transplantation. Compared with 14 pRTR renal transplant biopsies without significantly increased plasma cells, there were no significant differences in mismatch and baseline estimated glomerular filtration rate (eGFR). Plasma cells were present in case biopsies at a maximal density of 14-116 (median 33) plasma cells/HPF. Increased plasma cells were associated with decreased eGFR at biopsy (22 vs. 49 ml/min/1.73 m; p < 0.001) and 4 weeks post-biopsy (26 vs. 56 ml/min/1.73 m; p < 0.001) despite comparable eGFR 4 weeks prior to biopsy. Increased plasma cells were further associated with significantly increased frequency of renal allograft loss (71 % vs. 7 %; p < 0.001) at 0-27 (median 2) months after biopsy. Conclusion: Increased plasma cell infiltrates in pRTR are uncommon but associated with significantly reduced renal allograft survival as well as significantly reduced allograft function in surviving grafts. [ABSTRACT FROM AUTHOR]

Background: Previous studies in adult hemodialysis patients have shown that African-American and Hispanic patients have a lower risk of mortality in addition to a lower likelihood of kidney transplantation. However, studies of the association between race and outcomes in pediatric dialysis are sparse and often do not examine outcomes in Hispanic children. The objective was to determine if racial-ethnic disparities in mortality and kidney transplantation outcomes exist in pediatric dialysis patients. Methods: This was a retrospective cohort analysis of 2,697 pediatric dialysis patients (aged 0-20 years) from a large national dialysis organization (entry period 2001-2011) of non-Hispanic white, African-American, and Hispanic race-ethnicity. Associations between race-ethnicity with mortality and kidney transplantation outcomes were examined separately using competing risks methods. Logistic regression analyses were used to examine the association between race-ethnicity, with outcomes within 1 year of dialysis initiation. Results: Of the 2,697 pediatric patients in this cohort, 895 were African-American, 778 were Hispanic, and 1,024 were non-Hispanic white. After adjusting for baseline demographics, competing risk survival analysis revealed that compared with non-Hispanic whites, African-Americans had a 64 % higher mortality risk (hazards ratio [HR] = 1.64; 95 % CI 1.24-2.17), whereas Hispanics had a 31 % lower mortality risk (HR = 0.69; 95 % CI 0.47-1.01) that did not reach statistical significance. African-Americans also had higher odds of 1-year mortality after starting dialysis (odds ratio [OR] = 2.08; 95 % CI 0.95-4.58), whereas both African-Americans and Hispanics had a lower odds of receiving a transplant within 1 year of starting dialysis (OR = 0.28; 95 % CI 0.19-0.41 and OR = 0.43; 95 % CI 0.31-0.59 respectively). Conclusion: In contrast to adults, African-American pediatric dialysis patients have worse survival than their non-Hispanic white counterparts, whereas Hispanics have a similar to lower mortality risk. Both African-American and Hispanic pediatric dialysis patients had a lower likelihood of kidney transplantation than non-Hispanic whites, similar to observations in the adult dialysis population. [ABSTRACT FROM AUTHOR]

Background: Peritonitis is a severe complication of chronic peritoneal dialysis (CPD) in infants. Few studies have been conducted to evaluate the relationship between hypogammaglobulinemia and peritonitis risk, and the potential benefit of intravenous immunoglobulins (IVIG) therapy in infants receiving CPD. Methods: Patients aged 0-12 months at initiation of CPD between 1985 and 2012 were eligible for inclusion in this retrospective study. Data collected from the start of CPD up to 2 years post-dialysis initiation included patient demographics, dialysis characteristics, serum immunoglobulin (IgG) levels, IVIG administration history, infectious complications and outcomes. Cox regression analysis and linear mixed model analysis were used for statistical analysis. Results: Twenty-six consecutive patients were included in the study. Annualized peritonitis rates for infants aged 0-30 days (≤1-month age group; n = 16; 320.3 patient-months) and 31-365 days (>1-12-month age group; n = 10; 163.3 patient-months) at dialysis initiation were 0.27 (1 episode per 45.8 patient-months) and 0.15 (one episode per 81.7 patient-months), respectively. Seventy-six percent of the serum IgG levels were >1 standard deviation below the age-appropriate mean levels, and these did not differ in those who developed peritonitis versus those who did not ( p = 0.39). Serum IgG levels were significantly lower in patients on CPD with oligoanuria than in non-oliguric patients ( p = 0.04) and in patients on CPD for >90 days as compared to those who had received CPD for <90 days ( p = 0.018). IVIG therapy was provided to 20 patients with hypogammaglobulinemia; this high prevalence of IVIG usage precluded any drawing of conclusion on the potential role of IVIG in the prevention of peritonitis. Conclusions: Hypogammaglobulinemia is a frequent complication of CPD during infancy. In our experience, it was not associated with an increased risk for peritonitis. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to characterize the nutrient intake of children with chronic kidney disease (CKD) relative to recommended intake levels. Methods: We conducted a cross-sectional study of dietary intake assessed by Food Frequency Questionnaire (FFQ) in The North American Chronic Kidney Disease in Children (CKiD) prospective cohort study. Nutrient intake was analyzed to estimate the daily consumption levels of various nutrients and compared with national guidelines for intake. Results: There were 658 FFQs available for analysis; 69.9 % of respondents were boys, with a median age [Interquartile range (IQR)] of 11 years (8-15). Median daily sodium, potassium, and phosphorus intake was 3089 mg (2294-4243), 2384 mg (1804-3076), and 1206 mg (894-1612) respectively. Sodium and phosphorus consumptions were higher than recommended in all age groups. Caloric intake decreased with dropping glomerular filtration rate (GFR) ( p = 0.003). The median daily caloric intakes were 1307 kcal in male children 2-3 years old, 1875 kcal in children 4-8 years old, 1923 kcal in those 9-13 years old, and 2427 kcal in those 14-18 years old. Respective levels for girls were 1467 kcal, 1736 kcal, 1803 kcal, and 2281 kcal. Median protein intake exceeded recommended levels in all age groups, particularly among younger participants. Younger children were more likely than older children to exceed the recommended intakes for phosphorus ( p < 0.001) and the age-specific recommended caloric intake ( p < 0.001). Macronutrient distribution (carbohydrate:fat:protein) was consistent with recommendation. Conclusions: Children in the CKiD cohort consumed more sodium, phosphorus, protein, and calories than recommended. The gap between actual consumption and recommendations indicates a need for improved nutritional counseling and monitoring. [ABSTRACT FROM AUTHOR]

Background: Intradialytic hypotension and myocardial stunning are proposed as contributing to the pathogenesis of increased cardiovascular disease burden and death in patients receiving maintenance hemodialysis (HD). Noninvasive cardiac output measurements provide a dynamic, real-time assessment of hemodynamic parameters. We investigated intradialytic changes in hemodynamic parameters in pediatric outpatients receiving chronic HD and determined patient and treatment risk factors associated with such intradialytic changes. Methods: Hemodialysis was performed using linear fluid removal over 4 h with polysulfone dialyzers. Continuous wave Doppler ultrasound was used to measure hemodynamic parameters prior, 2 h into, and after the mid-week HD treatment session. Pulse wave tonometry was performed at the same time. The percentage change in blood volume was measured by noninvasive hematocrit monitoring during HD. Results: Twenty-two patients fit the inclusion criteria, of whom 16 (73 %) were male. The mean age of the patients was 17 ± 3.8 years, and the dialysis vintage was 47.8 ± 33.7 months. The cardiac index decreased significantly midway through the HD treatment session and remained low until the end of treatment. A significant decline in cardiac index without hypotension occurred in 12 (54 %) patients. Expected increase in systemic vascular resistance index to preserve the cardiac index was not observed. Weight, percentage fluid overload, dialysis vintage, and adequacy did not correlate with the observed decline in the cardiac index. The decrease in blood volume at the 2 h ( R = 0.43, p = 0.045) and 4 h ( R = 0.56, p = 0.007) time points was the only factor associated with cardiac index decline. Conclusion: The cardiac index and stroke volume decreased significantly during the HD session. Patients with larger blood volume changes during the first 2 h of HD and at 4 h showed a significant decrease in cardiac index that did not recover at the completion of the HD treatment. Rate of fluid removal was the only significant risk factor for compromised cardiac index during HD. Conventional methods currently used for assisting fluid removal in HD are inadequate to assess hemodynamic changes. [ABSTRACT FROM AUTHOR]

Objectives: Aminoglycosides (AG) are a group of bactericidal antibiotics with nephrotoxic effects that are commonly used in the treatment of hospitialized children. We have examined previous AG treatment as a risk factor for acute kidney injury (AKI) during current AG treatment. Study design: We performed a retrospective cohort study of children ranging in age from 1 month to 18 years who were treated with AG between October 2008 and April 2012 at Montreal's Children's Hospital. Children for whom no serum creatinine data (SCr) were available and those with baseline renal disease were excluded from the analysis. Main exposures were prior AG use (number and hours of prior treatments) and time since last AG treatment. The main outcome was AKI, defined on the basis of the Kidney Disease: Improving Global Outcomes guidelines. Logistic regression was used to examine exposure-outcome associations. Results: AG treatments episodes with Stage 1, 2, and 3 AKI, respectively, were associated with a median of 98 [interquartile range (IQR) 339], 231 (IQR 688), and 111 (IQR 505) h of prior AG treatment, respectively, versus non-AKI (median 0, IQR 54 h) ( p < 0.0001). AKI episodes were associated with a mean (± standard deviation) of 1.5 ± 1.8 AG treatments in the previous 6 months, versus 0.9 ± 1.6 AG treatments for non-AKI. The number of AG-treatment days during the preceding 6 months [adjusted odds ratio (adjOR) 1.04, 95 % confidence interval (CI) 1.03-1.06; p < 0.001], younger age (adjOR 0.96, 95 % CI 0.93-0.99; p = 0.009), admission to hematology-oncology department (adjOR 3.88, 95 % CI 2.17-6.96; p < 0.001), and tobramycin use (adjOR 1.77, 95 % CI 1.04-3.02; p = 0.04) were independently associated with AKI. Episodes with Stage 1 and 2 AKI were associated with fewer days since last treatment compared to non-AKI treatment ( p < 0.02 and p < 0.005, respectively; Mann-Whitney test). Conclusions: Based on these results, prior AG treatment is a risk factor for AKI and should be considered when dosing and monitoring hospitalized children being treated with AG. [ABSTRACT FROM AUTHOR]

Background: WT1 is one of the genes commonly reported as mutated in children with steroid-resistant nephrotic syndrome (SRNS). We analyzed genotype-phenotype correlations in pediatric SRNS patients with WT1 mutations. Methods: From 2001 to 2015, WT1 mutations were detected in 21 out of 354 children with SRNS by genetic screening (5.9 %). The patients were grouped into missense ( n = 11) and KTS splicing ( n = 10) mutation groups. Results: Nine (82 %) patients with missense mutations presented with congenital/infantile nephrotic syndrome, while 8 (80 %) with KTS splicing mutations presented with childhood-onset SRNS. Progression to end-stage renal disease (ESRD) was noted in all patients with missense mutations (median age, 2.6 months; interquartile range [IQR], 0.8 months to 1.7 years) and in 5 patients with KTS splicing mutations (median, 9.3 years; IQR, 3.3-16.5 years). Disorders of sexual development (DSDs) were noted in all 12 patients with a 46, XY karyotype and in only 1 of the 8 patients with a 46, XX karyotype. One patient developed a Wilms tumor and another developed gonadoblastoma. Three patients had a diaphragmatic defect or hernia. Conclusions: WT1 mutations manifest as a wide spectrum of renal and extra-renal phenotypes. Genetic diagnosis is essential for overall management and to predict the genotype-specific risk of DSDs and the development of malignancies. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) staging has been developed in the adult and pediatric populations, but these do not yet exist for the neonatal population. Metabolomics was utilized to uncover biomarkers of normal and AKI-associated renal function in preterm infants. The study comprised 20 preterm infants with an AKI diagnosis who were matched by gestational age and gender to 20 infants without an AKI diagnosis. Methods: Urine samples from pre-term newborn infants collected on day 2 of life were analyzed using broad-spectrum nuclear magnetic resonance (NMR) metabolomics. Multivariate analysis methods were used to identify metabolite profiles that differentiated AKI and no AKI, and to identify a metabolomics profile correlating with gestational age in infants with and without AKI. Results: There was a clear distinction between the AKI and no-AKI profiles. Two previously identified biomarkers of AKI, hippurate and homovanillate, differentiated AKI from no-AKI profiles. Pathway analysis revealed similarities to cholinergic neurons, prenatal nicotine exposure on pancreatic β cells, and amitraz-induced inhibition of insulin secretion. Additionally, a pH difference was noted. Both pH and the metabolites were found to be associated with AKI; however, only the metabotype was a significant predictor of AKI. Pathways for the no-AKI group that correlated uniquely with gestational age included aminoacyl-t-RNA biosynthesis, whereas pathways in the AKI group yielded potential metabolite changes in pyruvate metabolism. Conclusions: Metabolomics was able to differentiate the urinary profiles of neonates with and without an AKI diagnosis and metabolic developmental profiles correlated with gestational age. Further studies in larger cohorts are needed to validate these results. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression medication nonadherence has been associated with donor-specific antibodies and treatment-refractory rejection. Drug-level monitoring is a practical direct marker for nonadherence, as variations indicate erratic ingestion of medication. We previously reported that high variability in tacrolimus trough levels determined by the percent coefficient of variation (CV %) and standard deviation (SD) were associated with biopsy-proven rejection. We hypothesized that the CV % and SD in patients on a sirolimus/low-dose tacrolimus regimen may associate with self-reported medication nonadherence, rejection and donor-specific antibodies. Methods: In this pilot feasibility study, we studied 37 biopsies in 23 pediatric renal transplant patients on both sirolimus and tacrolimus immunosuppression; CV %, SD, de novo donor-specific antibodies, rejection, and self-reported adherence were examined. Results: A cut-off sirolimus CV % of 25 maximized the percentage of biopsies correctly classified as rejection (32 of 37, or 86 %, p = 0.001). A cut-off tacrolimus CV % of 31 maximized the percentage of correctly classified biopsies (25 of 37, or 68 %, p = 0.09). Among patients with both high sirolimus and tacrolimus CV %, 67 % developed de novo donor-specific antibodies ( p = 0.002) with a DQ predominance and 71 % reported nonadherence ( p = 0.05). Conclusions: In pediatric renal transplantation, sirolimus and tacrolimus CV % is a potential tool for monitoring patients at risk for allograft rejection and donor-specific antibodies secondary to medication nonadherence. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial prophylaxis is recommended for the prevention of urinary tract infections (UTI) in high-risk children. However, there is growing concern about the use of β-lactams as prophylaxis and subsequent development of antibiotic resistance. Methods: In this prospective, randomized, crossover controlled trial we compared cotrimoxazole (SXT) and second-generation cephalosporins (2GC) as UTI prophylaxis in children ranging in age from 1 to 60 months. Eligible patients were 1:1 randomized to receive either SXT or 2GC for the initial 6-month period (1 course), then switched to the other antimicrobial agent class for the subsequent course, with switching continuing after each course until the end of the study. Urethral orifice cultures (UOCs) were obtained at the time of switching antimicrobial prophylaxis. Results: Among 97 children (mean age 13.6 months) on prophylaxis, breakthrough UTIs occurred during 13.3 % (10/75) of SXT courses and 10.3 % (8/78) of 2GC courses ( p = 0.62). 2GC failed earlier than SXT (mean ± standard error: 0.81 ± 0.1 vs. 2.37 ± 0.36 months, respectively; p = 0.028). Pseudomonas aeruginosa and Enterococcus spp. were more frequently isolated after 2GC courses than after SXT courses [22.6 vs. 4.8 % ( p = 0.02) and 20.7 vs. 4.8 % ( p = 0.035), respectively]. Prophylaxis with 2GC significantly increased resistance to both 2GC and SXT, while SXT prophylaxis did not affect susceptibility to 2GC. Conclusions: While SXT and 2GC appear to be equally efficacious as UTI prophylaxis in children, the latter exert a broader effect on patients' flora and development of bacterial resistance, suggesting that SXT may be more appropriate for UTI prophylaxis than 2GC. [ABSTRACT FROM AUTHOR]

Background: Renal anomalies are common in patients with Bardet-Biedl syndrome (BBS), a renal cystic ciliopathy with multi-systemic features. Renal transplantation is indicated in cases of end-stage renal disease (ESRD), but transplant centers may be hesitant to perform the necessary transplant in light of the multitude of metabolic comorbidities these patients often face with the potential to complicate outcomes. Methods: Data from the Clinical Registry Investigating BBS (CRIBBS) were used to investigate renal transplant outcomes in the largest BBS cohort described to date. Results: Of the 206 patients enrolled in the CRIBBS, 21 children (10.2 %; 16 girls, 5 boys; median age 8.4 years) had been diagnosed with ESRD. Renal transplantation was performed in 18 of these individuals between 1982 and 2015, including repeat transplantation in some cases, for a total of 22 kidneys. Overall graft survival was 81.6 % at 1 year post-transplantation, 75.7 % at 5 years, 59 % at 10 years, and 49.2 % at 25 years. Patient survival was 94.4 % at 1 year post-transplantation, 87.2 % at 8 years, and 79.3 % at 25 years. Conclusions: At a median follow-up time of 97 months, relatively few complications of renal transplantation were reported in the patients of this study. However, body mass index was significantly elevated in transplanted individuals compared to non-transplanted individuals participating in CRIBBS at the most recent follow-up. Although the frequency of obesity and other manifestations of the metabolic syndrome warrant meticulous management in this high-risk population, favorable long-term outcomes suggest that renal transplantation is a viable option for patients with BBS and ESRD. [ABSTRACT FROM AUTHOR]

Objective: To describe the safety and efficacy of sodium polystyrene sulfonate (SPS) in pediatric patients with acute hyperkalemia. Methods: A retrospective chart review of all patients less than 18 years of age administered SPS for acute hyperkalemia at Texas Children's Hospital between 2011 and 2014. Results: Our cohort consisted of 156 patients (mean age 6.8 ± 6.1 years). The peak mean potassium concentration observed was 6.5 ± 0.77 mmol/l prior to administration of SPS. The mean SPS dose was 0.64 ± 0.32 g/kg. The majority (91 %) of the SPS doses were given orally. The nadir mean potassium concentration in the 48 h post-SPS was 4.7 ± 1.2 mEq/l, which occurred at 16.7 ± 14.7 h post-dose. In the 48 h following SPS administration, 68 (43 %) patients required at least one additional intervention after SPS dose. Patients who required an additional intervention after initial SPS dose differed significantly in weight, baseline serum potassium, and were more likely to have received SPS treatment via the rectal route. A gastrointestinal adverse event was documented in 24 (15 %) patients. Conclusions: SPS was used effectively and safely in the majority of patients in this report. However, it may not be appropriate as a first single-line agent in patients with severe acute hyperkalemia who require a greater than 25 % reduction in serum potassium levels or those at a high risk for cardiac arrhythmias. [ABSTRACT FROM AUTHOR]

Background: Prospective studies have established the mycophenolate mofetil (MMF) efficiency in childhood idiopathic nephrotic syndrome (INS) but reports on the long-term outcome are lacking. Moreover, the search for factors influencing its efficiency would be useful to define its place among the other treatments. Methods: We performed a monocentric retrospective study including 96 children with steroid-dependent INS followed for 4.7 years (median) (IQ 3-6) after the onset of MMF treatment. The characteristics of responder patients ( n = 74), as defined by a 50 % decrease of relapse rate and/or a 60 % decrease of steroid dose, and of non-responder patients ( n = 22) were compared by univariate analysis and multivariate logistic regression. Results: Withdrawal of prednisone was achieved in 48/96 patients after a median duration of 18.1 months (IQ 7.8-30.0) of MMF. Only 26/48 patients did not relapse under MMF alone. After MMF was stopped in these patients, only six remained in remission without any treatment at last follow-up. Responders had a shorter time to remission at the first flare (9.5 vs. 15 days, p = 0.02), a shorter disease duration prior to the onset of MMF (22.2 vs. 94.5 months, p = 0.001), and were younger at the MMF initiation (6.7 vs. 10.1 years, p = 0.02) than non-responder patients. The age of MMF initiation was an independent factor associated with efficiency (OR = 0.80, 95 % CI [0.69, 0.93], p < 0.01). Conclusions: MMF is more efficient in young patients treated early in the disease course. Nevertheless, MMF has no remnant effect while nearly all patients relapsed after withdrawal of the drug. [ABSTRACT FROM AUTHOR]

Background: Post-infectious glomerulonephritis (PIGN) usually follows a benign course, but few children have an atypical, severe presentation, and these exceptional cases have been linked to the dysregulation of the complement alternative pathway (CAP). There is a considerable overlap in the histopathological features of PIGN and C3 glomerulopathy (C3G), which is also associated with CAP dysregulation but has a poorer outcome. We hypothesized that PIGN and C3G define a disease spectrum, and that in the past there may be some children with C3G who were misclassified with PIGN before C3G was described as a separate disease entity. Methods: Children with PIGN ( n = 33) diagnosed between 1985 and 2010 who underwent a renal biopsy due to their unusual course were reviewed and of them, 8 were reclassified into C3G based on the current classification criteria. Outcome was based on the degree of proteinuria, C3 level, and renal function at follow-up. Results: Sixteen (72.7%) children with typical PIGN recovered completely as compared to only 2 (25%) with C3G. Of note, children with 'typical' PIGN had a more severe disease course at onset; however, the outcome at last follow up was favorable. Conclusions: Our results support the hypothesis that PIGN and C3G form a disease spectrum and have different long-term clinical implications and management strategies. [ABSTRACT FROM AUTHOR]

Background: There are a lack of studies describing a longitudinal association between preterm delivery and renal complications later in life. We assessed renal size and function in preterm infants born with extremely low birth weight (ELBW) during 4 years of follow-up, comparing these parameters to age-matched children born full term (term controls). Methods: The results of selected renal laboratory tests [levels of cystatin C, creatinine, blood urea nitrogen (BUN)] and of renal ultrasound evaluations were compared between the ELBW group and the term control group at age 7 and 11 years. Results: The study population consisted of 64 children born with ELBW (ELBW children) who had been recruited at birth and 36 children born at term (term children) who took part in both follow-up assessments. Renal ultrasound examination revealed a significantly smaller renal volume in the 7- and 11-year-old ELBW children compared to the term controls [right kidney volume: 50.8 vs. 61.2 ml/m, respectively, at 7 years ( p <0.01) and 51.4 vs. 58.2 ml/m, respectively, at 11 years ( p <0.01); left kidney volume: 51.4 vs. 60.3 ml/m, respectively, at 7 years ( p <0.01) and 55.2 vs. 60.7 ml/m, respectively, at 11 years ( p = 0.02)]. Renal function in ELBW children was also affected. Serum cystatin C levels were significantly higher in ELBW children than in the controls at 7 years of age, and this difference remained statistically significant at 11 years of age [0.63 vs. 0.59 mg/l, respectively, at 7 years ( p = 0.02) and 0.72 vs. 0.61 mg/l, respectively, at 11 years ( p = 0.01)]. Six ELBW children also had elevated cystatin C levels (0.97-1.11 mg/l) at 11 years of age. Cystatin C levels were within normal range in the ELBW children at age 7 years and in term children in both follow-up studies. BUN levels were higher in ELBW children at the age of 11 years (4.49 vs. 4.15 mmol/l; p = 0.028). Conclusion: Continued follow-up of these patients will reveal whether the observed worsening in renal function will persist into adulthood. [ABSTRACT FROM AUTHOR]

Background: Little information is currently available on the development of tubulointerstitial lesions in children with Henoch-Schönlein nephritis (HSN). To identify the impact of the development of tubulointerstitial changes in HSN, we retrospectively analyzed renal biopsies obtained from children with HSN. Methods: Twenty-eight children with HSN from whom serial renal biopsies had been obtained before and after immunosuppressive therapy were enrolled in the study. The patients were divided into two groups according to the observed change in tubulointerstitial lesion development: group I ( n = 15), with stable or improved tubulointerstitial lesions, and group II ( n = 13), with worsened tubulointerstitial lesions. Group II patients had longer duration of proteinuria than group I patients (3.7 ± 3.7 years vs. 1.7 ± 1.7 years, p = 0.052). Results: The change in serum albumin level was negatively correlated with the change in tubulointerstitial scores before and after treatment (γ = −0.444, p = 0.018). Group II patients showed a significant decrease in immunoglobulin G (IgG) and IgA deposits after treatment ( p = 0.039 and 0.003, respectively), while group II patients did not ( p = 0.458 and 0.506, respectively). Conclusions: Although the International Study of Kidney Disease in Children classification of HSN does not include tubulointerstitial lesions, they can progress during treatment and could have significant clinical implications in association with the duration of proteinuria. [ABSTRACT FROM AUTHOR]

Background: Due to lower complication rates in comparison to central venous catheter (CVC) arteriovenous fistulas (AVFs) are now the preferred hemodialysis access. Recommendations for the first access cannulation range from 6 to 12 weeks, which could lead to temporary or even permanent preference for CVC while awaiting the maturation of the newly created AVF. The aim of this study was to evaluate the influence of first cannulation of AVFs on primary (PP) and secondary (SP) patency rates in children on hemodialysis (HD). Methods: This was a retrospective cohort study of 42 pediatric patients with a median age of 14 (range 7-17) years. At the time of surgical AVF creation 21 patients (end-stage renal disease) were still on HD via CVC or peritoneal catheter, while 21 were pre-emptive with initiation of HD expected within a few weeks. All patients received an AVF by the same experienced surgeon between February 1993 and May 2014. Primary failure (PF) was defined as the inability to use the AVF even once due to absent maturation or occlusion within 4 weeks after creation. PP was defined as the interval from time of access placement to any intervention designed to maintain or reestablish patency, to access thrombosis or the time of measurement of patency, while SP was defined as the total lifespan from creation to access abandonment, end of follow-up or loss. Results: Primary failure was observed in six (14.3 %) of 42 AVFs (all radiocephalic fistulas) within the first 10 days after cannulation. Excluding PF, the PP/SP rates at 1, 3, 6, 12, 18 and 24 months were 100/100, 91/99, 86/98, 76/95, 55/85 and 44/77 %, respectively. There was a significant decrease in PP when first cannulation was performed within the first 30 days after creation compared to first cannulation performed after 30 days ( p = 0.004). In terms of PP/SP outcome and timing of the first cannulation, there was no significant difference in thee outcome of PP/SP between first cannulation within the first 45 days after creation and that after 45 days ( p = 0.091/0.883). Conclusions: The findings suggest that cannulation of AVF within 30 days after surgical creation reduces PP, while SP may be influenced less by time until cannulation. We also found no significant differences in PP after maturing periods of >45 days. [ABSTRACT FROM AUTHOR]

Background: Patients negative for Shiga toxin-producing E. coli (STEC) are categorized as having atypical hemolytic uremic syndrome (HUS) and are associated with an increased risk for complement mutations and poorer prognosis compared with typical HUS. However, STEC identification is limited by the natural history of HUS. Methods: The current study is aimed at identifying HUS patients with poor outcomes based on the presence or absence of diarrhea (D) or Shiga toxin (S). A single-center retrospective review (2003-2012) of 42 HUS patients (follow-up 31.3 ± 38.7 months) was carried out. HUS was managed clinically with supportive treatments such as dialysis, plasma therapy, and eculizumab. Results: There was no significant difference in the D+S+ (31 %), D+S− (50 %) and D−S− (19 %) groups in the outcome variables of chronic kidney disease stages I-II (100 % vs 81 % vs 67 %) and proteinuria at follow-up (20 % vs 12.5 % vs 33.3 %), hospitalization duration (16.0 ± 8.7 vs 18.1 ± 9.5 vs 23.7 ± 12.9 days); dialysis requirement (50 % vs 81 % vs 66.7 %), and dialysis duration (10.2 ± 1.9 vs 33.3 ± 72.8 vs 10.3 ± 8.1 days). There was no significant difference in study outcomes in STEC+ (59 %) versus STEC- (41 %) groups. Genetic testing was performed in 12 % of HUS patients based on age, recurrent HUS, familial HUS, persistently low C3, or prolonged dialysis, and 80 % of the patients tested were positive for genetic mutations. Conclusions: Our study does not show poorer outcomes in STEC− HUS. Indications and the cost-effectiveness of genetic testing, eculizumab, and plasmapheresis in STEC− HUS need to be evaluated further. [ABSTRACT FROM AUTHOR]

Background: The benefit of post-urinary tract infection (UTI) sonography to detect clinically significant renal abnormalities remains a subject open to debate. Decision curve analysis (DCA) is a novel method for evaluating the clinical usefulness of diagnostic tests. Our objective was to determine, using DCA, the benefit of post-UTI sonography and of post-UTI sonography with biological markers of inflammation to predict the risk of recurrence of febrile UTI in children aged 2 to 24 months without known uropathy. Methods: We retrospectively analyzed all children aged 2 to 24 months, without known uropathy, who presented with a first episode of febrile UTI between 2009 and 2012 and followed them for 30 months. We then used DCA to estimate the benefit of post-UTI sonography or post-UTI sonography + biological markers of inflammation for detecting the risk of recurrence. Results: A total of 318 children [144 boys (45.3 %) and 174 girls (54.7 %)], with a mean age of 6.9 ± 5.6 months, were identified. Of these, 210 children presented with a significant inflammation [66.2 %; 95 % confidence interval (CI) 61.0-71.4], and 30 (9.4 %; 95 % CI 6.2-12.6) presented with abnormal post-UTI sonographic findings. Eighteen (5.7 %; 95 % CI 3.1-8.2) children presented with recurrent UTI at 30 months. Conclusions: There were significantly more recurrences in those children who presented with abnormal sonographic findings than in those who did not (relative risk 7.68; 95 % CI 3.03-19.46). However, taking into account the effect of false-positives and false negatives, the DCA revealed that for threshold probabilities of >30 %, at which patients/doctors are concerned about unnecessary interventions (whether tests or treatments), neither post-UTI sonography nor post-UTI sonography + biological markers of inflammation have sufficient value to improve care. [ABSTRACT FROM AUTHOR]

Background: Left ventricular dysfunction is an important co-morbidity of end-stage renal disease (ESRD) and is associated with a poor prognosis in the adult population. In pediatric ESRD, left ventricular function is generally well preserved, but limited information is available on early changes in myocardial function. The aim of this study was to investigate myocardial mechanics in pediatric patients with ESRD using speckle-tracking echocardiography (STE). Methods: Echocardiographic studies, including M-mode, tissue Doppler imaging (TDI) and STE, were performed in 19 children on dialysis, 17 transplant patients and 33 age-matched controls. Strain measurements were performed from the apical four-chamber and the short axis view, respectively. Results: The interventricular and left ventricular posterior wall thickness was significantly increased in dialysis and transplant patients compared to healthy controls. No significant differences were found in shortening fraction, ejection fraction and systolic tissue Doppler velocities. Dialysis and transplant patients had a decreased mean longitudinal strain compared to healthy controls, with a mean difference of 3.1 [95 % confidence interval (CI) 2.0-4.4] and 2.7 (95 % CI 1.2-4.2), respectively. No differences were found for radial and circumferential strain. Conclusions: Speckle-tracking echocardiography may reveal early myocardial dysfunction in the absence of systolic dysfunction measured by conventional ultrasound or TDI in children with ESRD. [ABSTRACT FROM AUTHOR]

Background: Community-acquired urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging problem. Compared with urban infants, rural infants may encounter different distributions of community-acquired resistant strains and various barriers to efficient management. Methods: A retrospective survey and comparison was conducted for infants with UTI caused by ESBL-producing E. coli admitted to an urban hospital ( n = 111) and a rural hospital ( n = 48) in southern Taiwan from 2009 to 2012. Results: Compared with 2009 and 2010, the total number of cases at both hospitals significantly increased in 2011 and 2012 ( p < 0.001). Compared with the rural patients, the urban patients were significantly younger, and they had fewer days of fever before and after admission, fewer presentations of poor activity and poor appetite, and a lower serum creatinine level. Most of the patients had no prior history of illness, and we could not identify any significant different risk factors for acquiring ESBL-producing E. coli, such as past antimicrobial use, hospitalization, UTI, and underlying renal diseases, between the urban and rural populations. Conclusions: The increase in community-acquired UTI in infants caused by ESBL-producing E. coli was similar between the urban and rural populations. Our preliminary data suggest that the rural-urban disparities were probably related to easy access to health care by the urban population. ESBL complicates disease management, and the increase in the prevalence of ESBL producers is a major health concern and requires further healthy carrier and environmental surveillance. [ABSTRACT FROM AUTHOR]

Background: Contrast-induced acute kidney injury (CI-AKI) is a common pathology among adult patients, with an incidence ranging from 3-25 % depending on risk factors. Little information is available regarding CI-AKI incidence, risk factors, and prognostic impact in the pediatric population. Methods: We performed a retrospective study of pediatric patients who underwent computed tomography (CT) scan with iodinated contrast media injection between 2005 and 2014 in five pediatric units of a university hospital. CI-AKI was defined according to Kidney Disease/Improving Global Outcomes (KDIGO) criteria. Results: Of 346 identified patients, 233 had renal function follow-up and were included in our analyses. CI-AKI incidence was 10.3 % [95 % confidence interval (CI) 6.4-14.2 %]. CI-AKI was associated with 30-day unfavorable outcome before (45.8 % vs. 19.7 %, P = 0.007) and after [odds ratio (OR) 3.6; 95 % CI 1.4-9.5] adjustment for confounders. No independent risk factors of CI-AKI were identified. Conclusions: CI-AKI incidence was as high as 10.3 % following intravenous contrast media administration in the pediatric setting. As reported among adults, CI-AKI was associated with unfavorable outcome after adjustment for confounders. Although additional studies are needed in the pediatric setting, our data suggest that physicians should maintain a high degree of suspicion toward this complication among pediatric patients. [ABSTRACT FROM AUTHOR]

Background: Patients with sickle cell disease are at risk for developing chronic kidney disease (CKD). Acute kidney injury (AKI) has been linked to progression to CKD, but limited data exist to determine its role in acute complications of sickle cell disease. We hypothesized that AKI occurs in pediatric patients admitted for acute chest syndrome (ACS) and prolongs hospitalization. Methods: We conducted a 6-year retrospective review of pediatric patients with ACS admitted to a single medical institution. Results: Of the 149 pediatric patients admitted for ACS during the 6-year study period, 12 (8 %) developed AKI. Comparison of patients with and without AKI revealed a significant association between AKI and a larger drop in hemoglobin value from baseline (2.7 vs. 1.4 g/dL; p = 0.003), a lower hemoglobin value at admission (6.4 vs. 7.5 g/dL; p = 0.03), and an increased white blood cell count at admission (33.1 vs. 19.8 × 10/L; p < 0.0001), respectively. AKI ( p < 0.0001) together with need for advanced respiratory support (biphasic positive airway pressure or mechanical ventilation) ( p < 0.0001) and need for exchange transfusion ( p < 0.0001) were associated with prolonged hospitalization. Conclusions: Clinicians should monitor pediatric patients hospitalized for ACS for the development of AKI as a potentially modifiable risk factor for prolonged hospitalization. [ABSTRACT FROM AUTHOR]

Background: We investigated the prognostic value of overall and complement-binding donor-specific HLA antibodies (DSA) in pediatric patients undergoing clinically indicated graft biopsies and their association with graft outcome and specific histological lesions. Methods: Sera of 62 patients at time of indication biopsy ≥1 year posttransplant were assessed for DSA and C1q-fixing DSA by single-antigen bead (SAB) technology. Results: Twenty-six patients (42 %) were DSA-positive at time of indication biopsy and nine (15 %) were C1q-positive. At 4 years postbiopsy, patients with C1q-positivity had a low graft survival (11 %) compared to DSA-positive, C1q-negative patients (82 %, p = 0.001) and to DSA-negative patients (88 %, p < 0.001). The majority (89 %) of C1q-positive patients were diagnosed with active chronic antibody-mediated rejection (ABMR). C1q DSA-positivity [adjusted hazard ratio (HR) 6.35], presence of transplant glomerulopathy (HR 9.54), and estimated glomerular filtration rate (eGFR) at the time of indication biopsy (HR 0.91) were risk factors for subsequent graft loss. Conclusions: The presence of C1q-positive DSA in the context of an indication biopsy identifies a subgroup of pediatric renal transplant recipients with a markedly increased risk of subsequent graft loss. Because a fraction of DSA-positive patients escape rejection or graft dysfunction, the C1q assay increases the specificity of a positive DSA result regarding unfavorable transplant outcome. [ABSTRACT FROM AUTHOR]

Background: Little information is available regarding the clinical characteristics and prevalence of complications in children with chronic kidney disease (CKD), especially in early disease stages. The objective of this study was to determine the clinical characteristics and prevalence of complications in children with predialytic CKD. Methods: This multicenter, cross-sectional study enrolled children at all stages of predialytic CKD. Children who were between the ages of 1 year and 18 years and who fulfilled the clinical criteria of CKD were included in the study. Baseline demographic data, previous history, clinical characteristics, and laboratory data were collected. Results: A total of 757 children were included in the study. The median age at the time of enrollment was 10.6 years; 397 patients (52.4 %) were males. A total of 39.0 % of the patients were in CKD stage 1, 37.6 % were in stage 2, 14.8 % were in stage 3, 3.0 % were in stage 4, and 5.5 % were in stage 5. Nonglomerular renal diseases were the primary cause of CKD, comprising 51.9 % of the patients with CKD. The age at disease onset, gender, CKD stage distribution, and proportion of co-morbidities varied between the glomerular and nonglomerular CKD cases. Anemia, hyperlipidemia, hypocalcemia, and hyperphosphatemia were more prevalent in patients with glomerular CKD. The overall prevalence of complications was as follows: uncontrolled blood pressure, 44.1 %; anemia, 34.2 %; hyperlipidemia, 44.9 %; short stature, 10.3 %; and failure to thrive, 8.2 %. Uncontrolled blood pressure (BP), anemia, and hyperlipidemia were common, even in the early CKD stages. The prevalence of CKD complications generally increased with the worsening stage of CKD. Conclusions: This study reveals differences in CKD etiology and prevalence of specific complications according to the stage of CKD. Early recognition and awareness of complications are mandatory for clinicians during the follow-up visits of children with CKD. [ABSTRACT FROM AUTHOR]

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) <30 ml/min/1.73 m with receiver operator characteristic area under the curve (ROC-AUC) of 0.82; p = 0.002. When factored by urine creatinine CysC/cr + ALB/cr were the most significant functional markers with AUC = 0.79; p = 0.004; sensitivity 96 %; specificity 58 %. 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. [ABSTRACT FROM AUTHOR]

Background: To clarify the clinical manifestations of pediatric complement component C3 glomerulonephritis (C3GN), we retrospectively evaluated differences in the clinicopathological findings and prognosis between C3GN and immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN). Methods: Thirty-seven patients diagnosed with 'idiopathic MPGN' were enrolled in this retrospective study. The patients were divided into two groups, with Group 1 consisting of 19 patients diagnosed with IC-MPGN and Group 2 consisting of 18 patients diagnosed with C3GN. The clinical findings and the prognosis were investigated for both groups. Results: Thirteen patients in Group 2 were identified by mandatory annual school screening for urinary abnormalities. The incidence of macro-hematuria and the frequency of low serum C4 values were lower in Group 2 patients than in Group 1 patients. At the time of the second renal biopsy, urinary protein excretion, incidence of hematuria, frequency of low serum C3 values, and scores for mesangial proliferation, glomerular sclerosis, and interstitial fibrosis were higher in Group 2 patients than in Group 1 patients. At the most recent follow-up examination, the number of patients categorized as non-responding or with end-stage renal disease was higher in Group 2 patients than in Group 1 patients. Conclusions: Our results suggest that the treatment response and prognosis of patients with C3GN are worse than those of patients with IC-mediated MPGN. Therefore, in the clinical context regarding treatment options and prognosis, it may be useful to classify idiopathic MPGN as C3GN or IC-MPGN. In addition, long-term follow-up of C3GN is necessary. [ABSTRACT FROM AUTHOR]