Isolated Hydronephrosis and Urinary Tract Infection by Two Years of Age: A Population-Based Study.

OBJECTIVE: To evaluate the risk for urinary tract infection (UTI) in infants with isolated hydronephrosis (IH). STUDY DESIGN: A retrospective, population-based study including all infants insured by Clalit Health Services and followed from birth to age 2 years in 3 regions of central Israel. Infants were divided into 3 groups based on electronic medical record diagnoses by age 6 months: (1) control: no urological diagnosis; (2) IH; and (3) complicated urological diagnosis (CUD): any additional nephrological/urological diagnosis with/without HN. The primary outcome was a diagnosis of UTI in the first 2 years of life. RESULTS: The cohort included 340 619 infants (52% male): 333 920 controls, 4369 with IH, and 2331 with CUD. Infants with IH were associated with a greater risk for UTI than control patients (17% vs 4%, P < .001). UTI risk for a male infant with IH was greater than for a female infant in the control group (12.6% vs 6.5%, P < .001). In a multivariable logistic regression analysis, both IH (OR 7.04; 95% CI 6.46-7.66) and CUD (OR 14.9; 95% CI 13.6-16.4) were independently associated with UTI. CONCLUSION: Infants with IH are at a greater risk for UTI in the first 2 years of life, supporting the recommendation for a high index of suspicion for UTI in this population.

Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study.

To assess the long-term efficacy of burosumab for pediatric patients with X-linked hypophosphatemia, focusing on linear growth. This multi-center retrospective study included 35 pediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results, and Rickets Severity Score (RSS), from 2 years prior to treatment initiation and up to 4 years after. Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6-15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1-4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after 3 months and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8 to 90.1 ± 5.3% after 12 months of treatment (p = 0.041). The RSS improved from 1.7 ± 1.0 at burosumab initiation to 0.5 ± 0.6 and 0.3 ± 0.6 after 12 and 24 months, respectively (p < 0.001). Both height z-score and weight z-score improved from burosumab initiation to the end of the study: from - 2.07 ± 1.05 to - 1.72 ± 1.04 (p < 0.001) and from - 0.51 ± 1.12 to - 0.11 ± 1.29 (p < 0.001), respectively. Eight children received growth hormone combined with burosumab treatment. Height z-score improved among those who received growth hormone (from - 2.33 ± 1.12 to - 1.94 ± 1.24, p = 0.042) and among those who did not (from - 2.01 ± 1.01 to - 1.66 ± 1.01, p = 0.001). CONCLUSION:  Burosumab treatment in a real-life setting improved phosphate homeostasis and rickets severity and enhanced linear growth. WHAT IS KNOWN: • Compared to conventional therapy, burosumab treatment has been shown to increase serum phosphate levels and reduce the severity of rickets. • The effect of burosumab on growth is still being study. WHAT IS NEW: • Height z-score improved between the start of burosumab treatment and the end of the study (-2.07 ± 1.05 vs. -1.72 ± 1.04, p < 0.001). • Eight children received burosumab combined with growth hormone treatment without side effects during the concomitant treatments.

A Clinical Response-Adjusted Steroid Treatment Protocol for Children With Newly Diagnosed Idiopathic Nephrotic Syndrome.

RATIONALE & OBJECTIVE: Prednisone protocols for children with idiopathic nephrotic syndrome (INS) are generally similar in dose and duration, despite wide variations in time to response. We assessed the feasibility of a novel clinical treatment protocol characterized by a shorter duration and lower cumulative dose for children with early clinical response. STUDY DESIGN: Nonrandomized pilot clinical trial. SETTING & PARTICIPANTS: The study population included 59 children with newly diagnosed INS treated between 2014 and 2019 who responded to treatment within 8 days. INTERVENTION: The intervention group (n = 27) was treated with a response-adjusted protocol during which responders received an 8-week course of tapering doses of prednisone. The usual care group (n =32) was treated with the standard protocol (prednisone, 60 mg/m2/24 hours for 6 weeks, followed by 40 mg/m2/48 hours for 4 weeks, followed by a slow taper for a total of 24 weeks). OUTCOME: Consent rate, cumulative prednisone dose, the development of frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS, respectively), relapses per year, treatment with steroid-sparing therapies, and adverse effects of steroid therapy over 3 years of follow-up observation. RESULTS: The consent rate was 88%. The mean cumulative steroid dose for the initial treatment was 70 mg/kg and 141 mg/kg (P < 0.001) in the intervention and usual care groups, respectively. None of the patients in the intervention group relapsed while on faster steroid taper down. The occurrence of FRNS and SDNS in the intervention group was not statistically different than in the usual care group, hazard ratios were 0.80 (95% CI, 0.37-1.73) and 0.61 (95% CI, 0.30-1.27), respectively. The proportions of relapse-free patients were similar (P = 0.5), and adverse steroid events did not differ between the groups. LIMITATIONS: Lack of randomization and small sample size. CONCLUSIONS: These findings demonstrate the feasibility of a shortened duration of steroid dosing for INS when patients demonstrate an initial clinical response to treatment. A larger study is needed to characterize the relative efficacy and toxicity of this novel treatment regimen. FUNDING: This study received no funding. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCTO2649413.

EBV, CMV, and BK viral infections in pediatric kidney transplantation: Frequency, risk factors, treatment, and outcomes.

BACKGROUND: Improved short- and long-term outcomes of kidney transplantation have been achieved over the past decades due to improved immunosuppression. This may have increased the risk for infections and, particularly, for the viral infections: cytomegalovirus (CMV), Epstein-Barr virus (EBV), and polyoma BK virus (BKV). METHODS: A retrospective review of viremic CMV, EBV, and BKV infections in pediatric renal transplant recipients treated and followed by a national referral center over a 10-year period. RESULTS: Sixty-seven patients (68% males) received 68 kidney grafts (62% from living donors) during the study period; the mean follow-up period was 5.2 ± 2.4 years. Twenty-seven viremic episodes were documented (CMV: 13, EBV: 6, BKV: 8) in 24 patients (35.2%). The median time (interquartile range) to viremia post-transplant was 11 (4-38) months. The viral infection rate was significantly higher in the years 2014-2015 than in previous years (61% vs. 29%, p = .017). Compared to patients who did not develop viremia, patients with viremias were younger at the time of transplantation, were more likely to receive thymoglobulin induction pre-transplant and to develop an acute rejection. Multiple logistic regression modeling identified transplant year and recipient's age as significant risk factors for viremia. Graft outcome and eGFR at the last follow-up was similar between patients who did and did not develop viremia. CONCLUSIONS: Viral infections continue to be a major cause of morbidity in pediatric kidney transplant recipients. However, with close monitoring and prompt intervention, patient and renal outcomes remain favorable.

Use of Point-of-Care Ultrasound for Evaluation of Extravascular and Intravascular Fluid Status in Pediatric Patients Maintained on Chronic Hemodialysis.

AIMS: Traditional methods that use clinical parameters to determine dry weight in hemodialysis patients are inaccurate. This study aimed to compare clinical assessment of fluid status to sonographic parameters of fluid status in pediatric patients undergoing chronic hemodialysis. METHODS: In a prospective observational study, pediatric patients maintained on chronic hemodialysis (ages 2.3-20 years) were evaluated clinically and sonographically before and after dialysis at 6 consecutive sessions. Sonographic parameters examined were number of lung B-lines as a measure of extravascular volume and inferior vena cava (IVC)/aorta ratio as a measure of intravascular volume. Clinical assessment of fluid status was compared to sonographic assessment. RESULTS: Twelve patients were evaluated during 72 dialysis sessions. Sonographic parameters were significantly lower post-dialysis than pre-dialysis (B-lines number 4.5 ± 5 vs. 7.69 ± 7.46, p < 0.0001; IVC/aorta ratio 0.9 ± 0.2 vs. 1.1 ± 0.2, p < 0.0001, respectively). Ultrafiltration volume correlated with change in B-lines number during dialysis (r = 0.39, p < 0.01). Percent of blood volume drop correlated with post-dialysis IVC/aorta ratio (r = 0.48, p < 0.001). A higher percent of symptomatic episodes occurred with post-dialysis IVC/aorta ratio <0.8 versus ≥0.8 (39.1 vs. 15.2%, p = 0.036). Four patients were hypertensive, a clinical parameter implying fluid overload, in only one sonographic evaluation indicated fluid overload. Eight patients were clinically determined to be euvolemic, in three of them sonographic evaluation discovered covert fluids. CONCLUSION: Bedside ultrasound is a single modality that can be used to assess both extravascular and intravascular fluid status. It may contribute to clinical decisions differentiating fluid-related versus fluid-unrelated hypertension and identifying patients with covert fluids.

Is the prognosis of congenital single functioning kidney benign? A population-based study.

BACKGROUND: We investigated the risk of kidney injury among adolescents with and without a congenital single functioning kidney (SFK). METHODS: This retrospective study is based on a medical evaluation database of 17-year-old Israeli conscripts, born during 1989-1999. Those with congenital SFK diagnosis, verified by a pediatric nephrologist's review of the original military medical committee classifications, were compared to the rest of the cohort. Kidney injury (KI) was defined as proteinuria, high blood pressure (BP), or estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2 prior to army recruitment. Risk factors for KI were examined using logistic regression. RESULTS: Of 979,630 screened candidates, 353 were diagnosed with SFK. The yearly incidence of SFK gradually increased in the first years of the study, reaching a plateau in 1995 (5.5 ± 1.2/10,000 births/year). The male to female ratio was 2.7:1. Concomitant genital malformations were documented in 5.5% of those with SFK. KI was more prevalent in the SFK than the control group (42.2% vs. 23.5%, p < 0.001). All three components of KI were more common in the SFK than the control group: high BP (31.7% vs. 23.1%, p < 0.001), proteinuria (18.2% vs. 0.4%, p < 0.001), and eGFR <90 ml/min/1.73m2 (12.0% vs 0.1%, p < 0.001). Multivariate analysis of the SFK group revealed associations of higher mean BMI, male sex, and smaller ultrasonographic kidney length with KI. CONCLUSIONS: This large population-based study documents a significant risk for KI among adolescents with SFK. Obesity represents a major modifiable risk factor for KI, implicating the need for closer follow-up in this group during childhood.

[NEPHROTIC SYNDROME RECURRENCE POST-RENAL TRANSPLANTATION: 10 YEARS' EXPERIENCE AT SCHNEIDER CHILDREN'S MEDICAL CENTER IN ISRAEL].

INTRODUCTION: A total of 30-50% of pediatric patients presenting with steroid resistant nephrotic syndrome (SRNS) will reach end stage renal disease (ESRD). In patients with primary SRNS, the risk of post-transplant recurrence is around 60% with poor graft outcomes. In the past decade new treatment modalities have emerged in an attempt to improve graft outcomes. AIMS: To describe the clinical experience at the Schneider Children's Medical Center in Israel in treating children with post-transplant recurrent SRNS in the past decade, and compare its results to a similar study conducted at the same center in previous years. METHODS: A retrospective chart review was conducted. Data regarding demographic characteristics, clinical course and treatment modalities of patients with post-transplant recurrent SRNS were extracted from patients' charts. RESULTS: Eight patients with post-transplant recurrent SRNS were identified. Median age at initial nephrotic syndrome presentation was 4 (range: 0.8-15) years. Median time to reach ESRD was 43 (range: 12-132) months. All patients were treated with plasmapheresis, seven patients were treated with Rituximab. Low-density lipoprotein (LDL) apheresis, Ofatumumab and Abatacept were used in 1-2 patients each. Median follow-up time post-transplant was 47 (range: 15-93) months. Four patients (50%) responded to treatment, two achieved complete and two partial remission. Four patients reached ESRD within a median time of 24 (range: 12-84) months. Lower rates of acute tubular necrosis and immediate graft loss were observed during the last decade compared to previous years (37.5% vs. 64%; 0% vs. 28.6% respectively). CONCLUSIONS: Post-transplant recurrence of SRNS continues to pose a significant treatment challenge. Similar to previous reports, only 50% of our patients responded to treatment while 50% were unresponsive to all treatment modalities and reached ESRD. Immediate post-operative management improved over the last decade, however long-term outcome continues to be grim. There is a need to better identify disease mechanisms that will allow us to tailor more effective treatment modalities to improve patients' outcome.

Serologic response to COVID-19 infection or vaccination in pediatric kidney transplant recipients compared to healthy children.

BACKGROUND: Differences in serologic response to COVID-19 infection or vaccination were reported in adult kidney transplant recipients (KTR) compared to non-immunocompromised patients. This study aims to compare the serologic response of naturally infected or vaccinated pediatric KTR to that of controls. METHODS: Thirty-eight KTR and 42 healthy children were included; aged ≤18 years, with a previously confirmed COVID-19 infection or post COVID-19 vaccination. Serological response was measured by anti-spike protein IgG antibody titers. Response post third vaccine was additionally assessed in KTR. RESULTS: Fourteen children in each group had previously confirmed infection. KTR were significantly older and developed a 2-fold higher antibody titer post-infection compared to controls [median (interquartile range [IQR]) age: 14.9 (7.8, 17.5) vs. 6.3 (4.5, 11.5) years, p = 0.02; median (IQR) titer: 1695 (982, 3520) vs. 716 (368, 976) AU/mL, p = 0.03]. Twenty-four KTR and 28 controls were vaccinated. Antibody titer was lower in KTR than in controls [median (IQR): 803 (206, 1744) vs. 8023 (3032, 30,052) AU/mL, p < 0.001]. Fourteen KTR received third vaccine. Antibody titer post booster in KTR reached similar levels to those of controls post two doses [median (IQR) 5923 (2295, 12,278) vs. 8023 (3034, 30,052) AU/mL, p = 0.37] and to KTR post natural infection [5282 AU/mL (2583, 13,257) p = 0.8]. CONCLUSION: Serologic response to COVID-19 infection was significantly higher in KTR than in controls. Antibody level in KTR was higher in response to infection vs. vaccination, contrary to reports in the general population. Response to vaccination in KTR reached levels comparable to controls only after third vaccine.

Children with Intestinal Failure Maintain Their Renal Function on Long-Term Parenteral Nutrition.

BACKGROUND: Long-term parenteral nutrition (PN) has been associated with renal complications, including hypercalciuria, nephrocalcinosis, proteinuria and reduced glomerular filtration rate (GFR). Pediatric data are scarce and mostly short-term. Our study aimed to evaluate renal complications in children with intestinal failure (IF) receiving long-term PN. METHODS: A cross-sectional study was performed in a tertiary pediatric IF clinic of patients receiving home-PN treatment for more than 1 year. Data regarding medical background, anthropometrics, laboratory investigations and abdominal sonography were retrieved. RESULTS: Complete data were available for 15 children (67% males), with a median age of 6 (range 1.5-15) years and a median (IQR) PN duration of 4 (1.5-6) years. Low-grade proteinuria was identified in 61% and microalbuminuria in 30% of the cohort. Hypercalciuria and hyperoxaluria were present in 50% and 46%, respectively. One patient had nephrocalcinosis. The estimated GFR was normal in all but one patient who had pre-existing kidney disease. CONCLUSIONS: Pediatric IF patients can present with preserved kidney function after years of PN treatment. Despite the high prevalence of hypercalciuria, nephrocalcinosis was not common. Base line and long-term monitoring of various aspects of renal function would be essential to characterize the effects of prolonged PN on kidney functions in pediatric patients.

Childhood Hypercalciuric Hypercalcemia With Elevated Vitamin D and Suppressed Parathyroid Hormone: Long-Term Follow Up.

Purpose: Hypercalcemia with low parathyroid hormone (PTH) level, hypercalciuria, nephrocalcinosis, or nephrolithiasis, was recently reported as caused by mutations in CYP24A1 and SLC34A genes. These encode for vitamin D-24A-hydroxylase and for the renal phosphate transporters NaPiIIa and NaPiIIc, respectively. We aimed to describe the clinical course of these monogenic disorders in patients with and without found mutations during long-term follow-up. Methods: Ten patients with hypercalcemia, hypercalciuria, elevated 1,25-(OH)2D levels and suppressed PTH were followed in our center during 1998-2019. Relevant laboratory and imaging data and results of genetic evaluation were retrieved from medical files. Results: The median age at presentation was 9.5 months (range 1 month-11 years), six were males, and the median follow-up time was 3.8 (1.1-14) years. Mutations in CYP24A1 and SLC34A3 were identified in three and one patients, respectively. Five patients presented with nephrocalcinosis, three with nephrolithiasis, and two had normal renal ultrasound. High blood calcium and 1,25-(OH)2D levels at presentation decreased during follow-up [11.1 ± 1 vs. 9.9 ± 0.5 mg/dl (p = 0.012), and 307 ± 130 vs. 209 ± 65 pmol/l (p = 0.03), respectively]; this paralleled an increase in suppressed PTH levels (5.8 ± 0.9 vs. 11.8 ± 7.3 pg/ml, p = 0.2). Substantial improvements in hypercalciuria and renal sonography findings were not observed. Two patients had impaired renal function (eGFR 84-88 ml/min/1/73 m2) at the last follow up. Interventions included appropriate diet, citrate supplementation, and thiazides. Conclusion: Despite improvement in hypercalcemia and 1,25-(OH)2D levels, not all the patients showed improvements in hypercalciuria and nephrocalcinosis. Deterioration of renal function was also observed. Long-term follow up and intervention to prevent nephrocalcinosis and nephrolithiasis are recommended in these children.

Clinical Outcomes and Antibody Response in COVID-19-Positive Pediatric Solid Organ Transplant Recipients.

We describe the clinical and laboratory manifestations and outcomes of 25 pediatric solid organ transplant recipients who tested positive for severe acute respiratory coronavirus-2. Twenty-one (84%) developed a mild disease; 22 of 23 (96%) had a positive serologic response. Two patients (8%), both kidney transplant recipients with additional comorbidities, developed a severe disease. The findings emphasize the need for close monitoring of this population.

Serological Response to the BNT162b2 COVID-19 mRNA Vaccine in Adolescent and Young Adult Kidney Transplant Recipients.

BACKGROUND: Initial reports in adult kidney transplant recipients (KTR) indicate low immunogenicity after 2 doses of the BNT162b2 COVID-19 mRNA vaccine. We describe the immunogenicity of this vaccine compared to the serologic response in naturally infected COVID-19 positive adolescent and young adult KTR. METHODS: For this prospective observational study, the study group included 38 KTR who received 2 doses of the tested vaccine, and the control group included 14 KTR who had a previous polymerase chain reaction-confirmed COVID-19 infection. RESULTS: The mean age was 18 ± 3 y. Positive serologic responses were observed in 63% and 100% of the study and control groups, respectively (P = 0.01). Antibody titers were almost 30-fold higher in the control than the study group (median [interquartile range (IQR)]: 2782 [1908-11 000] versus 100.3 [4.7-1744] AU/mL, P < 0.001), despite the longer time from the COVID-19 infection to serologic testing compared to time from vaccination (median [IQR]: 157.5 [60-216] versus 37 [20.5-53] d, P = 0.011). Among vaccinated patients, higher proportions of those seronegative than seropositive were previously treated with rituximab (50% versus 8%, P = 0.01). Time from the second vaccine dose to serologic testing was longer in seropositive than seronegative patients (median [IQR]: 24.5 [15-40] versus 46 [27-56] d, P = 0.05). No patient developed symptomatic COVID-19 disease postvaccination. CONCLUSIONS: The BNT162b2 COVID-19 mRNA vaccine yielded higher positive antibody response in adolescent and young adult KTR than previously reported for adult KTR. Antibody titers after vaccination were significantly lower than following COVID-19 infection. Longer time may be required to mount appropriate humoral immunity to vaccination in KTR.