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.

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.

A multidisciplinary nephrogenetic referral clinic for children and adults-diagnostic achievements and insights.

BACKGROUND: Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty; however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetics clinic to apply a multidisciplinary model. METHODS: Patients were referred from different pediatric or adult nephrology units across the country if their primary nephrologist suspected an undiagnosed genetic kidney disease. We determined the diagnostic rate and observed the effect of diagnosis on medical care. We also discuss the requirements of a nephrogenetics clinic in terms of logistics, recommended indications for referral, and building a multidisciplinary team. RESULTS: Over 24 months, genetic evaluation was completed for a total of 74 unrelated probands, with an age range of 10 days to 72 years. The most common phenotypes included congenital anomalies of the kidneys and urinary tract, nephrotic syndrome or unexplained proteinuria, nephrocalcinosis/nephrolithiasis, tubulopathies, and unexplained kidney failure. Over 80% of patients were referred due to clinical suspicion of an undetermined underlying genetic diagnosis. A molecular diagnosis was reached in 42/74 probands, yielding a diagnostic rate of 57%. Of these, over 71% of diagnoses were made via next generation sequencing (gene panel or exome sequencing). CONCLUSIONS: We identified a substantial fraction of genetic kidney etiologies among previously undiagnosed individuals which influenced subsequent clinical management. Our results support that nephrogenetics, a rapidly evolving field, may benefit from well-defined multidisciplinary co-management administered by a designated team of nephrologist, geneticist, and bioinformatician. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Long-term outcomes during 37 years of pediatric kidney transplantation: a cohort study comparing ethnic groups.

BACKGROUND: This study aimed to evaluate short- and long-term outcomes of kidney transplantation over 37 years in a national referral center and compare outcomes between Israeli Jewish and Arab children. METHODS: Data on 599 pediatric transplantations performed in 545 children during 1981-2017, including demographic parameters, kidney failure disease profile, and pre-transplant dialysis duration, were retrieved from our computerized database and patient files. Patient and graft survival were estimated using the Kaplan-Meier method. RESULTS: Twenty-year patient survival was 91.4% for live donor (LD) and 80.2% for deceased donor (DD) kidney recipients. Respective 10-year and 20-year graft survival rates for first kidney-only transplants were 75.2% and 47.0% for LD and 60.7% and 38.4% for DD grafts. Long-term graft survival improved significantly (p < 0.001) over the study period for recipients of both LD and DD allografts and reached 7-year graft survival of 92.0% and 71.3%, respectively. The proportion of DD transplantations was higher in the Arab subpopulation: 73.8% vs. 48.4% (p < 0.001). Graft survival was not associated with age at transplantation and did not differ between the Arab (N = 202) and Jewish children (N = 343). Median (IQR) waiting time on dialysis did not differ significantly between the Arab and Jewish children: 18 (10-30) and 15 (9-30) months, respectively (p Mann-Whitney = 0.312). CONCLUSIONS: Good and progressively improving long-term results were obtained in pediatric kidney transplantation at our national referral center, apparently due to expertise gained over time and advances in immunosuppression. Equal access to DD kidney transplant and similar graft survival were found between ethnic groups.

[PRIMARY HYPERTENSION IN CHILDREN AND ADOLESCENTS].

INTRODUCTION: The prevalence of pediatric primary hypertension (HTN) has increased in the past few decades, most probably related to the increased prevalence of overweight/obesity in this population. According to various estimates 3.5-5% of children and adolescents have HTN. Children and especially adolescents with HTN are at an increased risk for HTN in early adulthood, and for early subclinical cardiovascular morbidity. Therefore, screening for and treatment of pediatric HTN is highly recommended, especially in high risk populations, such as overweight children. In the past few years, new guidelines for the diagnosis, evaluation and treatment of pediatric HTN were published by both the European Society of Hypertension and the American Academy of Pediatrics. The following review will discuss central aspects of the epidemiology, risk factors, definitions, and initial clinical approach of primary HTN in children and adolescents.

[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.

Lower prednisone dosing for steroid-sensitive nephrotic syndrome relapse: a prospective randomized pilot study.

Relapses of steroid-sensitive nephrotic syndrome are traditionally treated with prednisone 2 mg/kg/day or 60 mg/m2/day. Retrospective data support the use of lower doses. We designed a prospective randomized pilot study to investigate the efficacy of different doses in achieving remission of steroid sensitive nephrotic syndrome relapse. The cohort included 30 children with relapsed steroid sensitive nephrotic syndrome, mean age 6.3 ± 3 years and mean disease duration 2.2 ± 1.8 years. The children were randomized to receive 2, 1.5, or 1 mg/kg/day prednisone. The corresponding times to response, defined as the first of 3 consecutive days without proteinuria, were 7.2 ± 1.4, 10.2 ± 5.1, and 9 ± 3.3 days; the difference between the 1.5 and 2 mg/kg/day groups was statistically significant. One patient each in the 1 mg/kg/day and the 1.5 mg/kg/day groups failed to respond and were switched to 2 mg/kg/day, leading to a response after 3 and 10 days, respectively. Mean cumulative prednisone doses in the 3 groups were 45.5 ± 3.4, 42.7 ± 25.9, and 24.9 ± 7.4 mg/kg, respectively (P < 0.05).Conclusion: In the present study, treatment of childhood steroid sensitive nephrotic syndrome relapse with prednisone 1-1.5 mg/kg/day led to a significantly lower cumulative dose than the standard dose. Treatment with a lower dose may be equally safe and effective to the standard dose.What is Known:• Relapses of steroid-sensitive nephrotic syndrome are traditionally treated with standard-dose steroids.• Treatment with corticosteroids may have significant adverse effects mainly with long-term use.What is New:• Treatment of steroid sensitive nephrotic syndrome relapse with 1-1.5 mg/kg/day prednisone may lead to a significantly lower cumulative dose.• Treatment with a lower steroid dose may be as effective as the standard dose in achieving remission of steroid sensitive nephrotic syndrome relapse.

Increasing Prevalence of Nephrolithiasis in Association with Increased Body Mass Index in Children: A Population Based Study.

PURPOSE: Epidemiological studies demonstrate an association of increased body mass index and risk of kidney stone formation in adults. We conducted a population based pediatric study to examine the epidemiology of nephrolithiasis in Israeli children during a 30-year period, and to determine body mass index distribution during the same period. MATERIALS AND METHODS: We accessed data from the compulsory medical evaluations of 17-year-old military service candidates in Israel before their enlistment during 1980 to 2013. Candidates for the army with a history of stone disease were compared to those without such a history. RESULTS: Of 1,908,893 candidates 1,691 reported a history of nephrolithiasis, yielding an average prevalence rate of 88.6 per 100,000. During 1980 to 1995 the average reported prevalence of nephrolithiasis was 69 cases per 100,000. From 1995 onward the reported prevalence increased by an average of 6% yearly, reaching 120 per 100,000 during 2010 to 2012. This increased prevalence was observed for males and females but was more prominent among males. Mean ± SD body mass index of stone formers was higher than that of controls (22.7 ± 3.5 vs 22.1 ± 3.9 kg/m2, p <0.001). The trend of increasing body mass index among male candidates during 1995 to 2012 parallels the trend of increasing nephrolithiasis during these years. The odds ratio for nephrolithiasis in candidates with body mass index 30 or greater kg/m2 was 1.7 (range 1.4 to 2.1) compared to candidates with a body mass index of 18.5 to 24.9 kg/m2. CONCLUSIONS: This large, population based study documents an increasing prevalence of nephrolithiasis in children. The possible association of this finding with the increase in body mass index during the same period warrants further investigation.

Focal segmental glomerulosclerosis in pediatric kidney transplantation: 30 years' experience.

From 1982 to 2011, 53 kidney transplantations (KT) for pediatric focal segmental glomerulosclerosis (FSGS) were recorded in the National Israeli Kidney Transplant Registry (NIKTR): 22-primary (1◦) FSGS, 25-proved/suspected genetic-secondary (2◦) FSGS, six lost/incomplete files/other. Half (56%) of 23 patients with 2◦ FSGS were Israeli-Arabs vs 29% of 1◦ FSGS KT recipients. 1◦ FSGS recurrence occurred in 64% (14/22) of 22 KT in 17 patients aged (median) 14 years vs 1/25 of 2◦ FSGS (P<.001). Early graft days/nonfunction occurred in 9/14 (64%), 2/8 (25%) and 2/25 (4%) of recurrent 1◦ FSGS (rFSGS), nonr1◦ FSGS and 2◦ FSGS, respectively. Twelve biopsies performed in nine of these grafts at (median) 8 days (range 5-60 days) post-KT showed: ATN-5, suspected rejection-4, rFSGS-2, normal kidney-1; rFSGS was diagnosed eventually in 8/9. Dialysis need during the first month post-KT was significantly associated with FSGS recurrence: 6/14 (43%) for rFSGS vs 2/8 (25%) for non-rFSGS. Plasmapheresis (PP) achieved complete and partial rFSGS remission in 5/9 and 2/9 grafts, respectively. Three grafts were excised during the first 60 days post-KT for: nonfunction (1) and bleeding (2). Remaining grafts' GFR was: 78, 42, and 91 mL/min (median) at 5.3, 4.75, and 8 years follow-up for non-rFSGS, rFSGS, and 2◦ FSGS grafts, respectively. CONCLUSIONS: Early PP implementation should be considered after KT for 1◦ FSGS patients with early graft dysfunction despite delayed proteinuria and nonspecific biopsy.

Anemia and markers of erythropoiesis in pediatric kidney transplant recipients compared to children with chronic renal failure.

PTA and anemia of CKD share a similar pathogenesis. However, PTA may be disproportionate to the reduction in the GFR. Data relating to the mechanism of PTA are scarce. We evaluated the erythropoiesis parameters in pediatric kidney recipients compared to children with CKD. A total of 100 patients (54 post-kidney TX, 46 with CKD) were enrolled in the single-center cohort study. GFR was found to be significantly lower in the CKD group (49.7±22.4 vs 72.9±28.5 mL/min/1.73 m², P<.001); anemia was significantly more common in the TX patients (52% vs 41.3%, P<.001). Iron transferrin saturation and serum ferritin levels were lower in the CKD patients. In both groups, hemoglobin Z scores significantly correlated with GFR (R=.31, P=.07). This correlation was more prominent in the CKD group (R=.43, P=.008) compared to the TX group (R=.31, P=.04). Anemia was significantly more common in the TX patients than in the CKD patients despite a better GFR. The higher prevalence of anemia in the TX group could not be explained by an iron deficiency or reduced EPO production. We speculate that immunosuppressive therapy together with resistance to EPO may play a role in the pathogenesis of post-transplantation anemia.

Is serum CRP level a reliable inflammatory marker in pediatric nephrotic syndrome?

BACKGROUND: This study tested the hypothesis that during massive proteinuria, C-reactive protein (CRP) may be lost into the urine along with other proteins, making serum CRP (sCRP) level an unreliable marker of infection severity in nephrotic syndrome (NS). METHODS: Children with active NS (n = 23) were compared with two matched control groups: patients with febrile non-renal infectious disease (n = 30) and healthy subjects (n = 16). Laboratory measurements included sCRP, urine protein, creatinine, IgG, and protein electrophoresis. Urinary CRP (uCRP) was measured by ELISA. RESULTS: Sixty-nine patients were enrolled: 23 patients with NS, 30 patients with non-renal febrile infectious diseases, and 16 healthy children. Median uCRP concentrations were 0 mcg/gCr (0-189.7) in NS, 11 mcg/gCr (0-286) in the febrile group, and 0 mcg/gCr (0-1.8) in the healthy group. The uCRP/creatinine ratio was similar in the NS and healthy groups (p > 0.1) and significantly higher in the febrile group than the other two groups (p < 0.0001). There was no association of uCRP concentration with severity of proteinuria or IgG excretion. CONCLUSIONS: NS in children is not characterized by significant loss of CRP into the urine. Therefore, sCRP may serve as a reliable marker of inflammation in this setting. The significant urinary excretion of CRP in children with transient non-renal infectious disease might be attributable to CRP synthesis in renal epithelial cells.

Improvement in Creatinine Clearance after Open Heart Surgery in Infants as an Early Indicator of Surgical Success.

BACKGROUND: Early surgical correction of congenital heart malformations in neonates and small infants may be complicated by acute kidney injury (AKI), which is associated with higher morbidity and mortality rates, especially in patients who require dialysis. Glomerular filtration rate (GFR) is considered the best measurement of renal function which, in neonates and infants, is highly dependent on heart function. OBJECTIVES: To determine whether measurements of creatinine clearance after open heart surgery in neonates and young infants can serve as an early indicator of surgical success or AKI. METHODS: We conducted a prospective observational study in 19 neonates and small infants (body weight < 5 kg) scheduled for open heart surgery with cardiopulmonary bypass. Urine collection measurement of creatinine clearance and albumin excretion was performed before and during surgery and four times during 48 hours after surgery. RESULTS: Mean creatinine clearance was lowest during surgery (25.2 ± 4. ml/min/1.73 m2) and increased significantly in the first 16 hours post-surgery (45.7 ± 6.3 ml/min/1.73 m2). A similar pattern was noted for urine albumin which was highest during surgery (203 ± 31 µg/min) and lowest (93 ± 20 µg/min) 48 hours post-surgery. AKI occurred in four patients, and two patients even required dialysis. All six showed a decline in creatinine clearance and an increase in urine albumin between 8 and 16 hours post-surgery. CONCLUSIONS: In neonates and small infants undergoing open heart surgery, a significant improvement in creatinine clearance in the first 16 hours postoperatively is indicative of a good surgical outcome. This finding has important implications for the early evaluation and treatment of patients in the intensive care unit on the first day post-surgery.

Plant-related Philistine ritual practices at biblical Gath.

The Philistine culture (Iron Age, ca. 1200-604 BCE) profoundly impacted the southern Levant's cultural history, agronomy, and dietary customs. Nevertheless, our knowledge of the Philistines' cultic praxis and deities, is limited and uncertain. Here, we combine archaeological data with a meticulous study of plant use at two successive temples at Tell es-Sâfi/Gath. We provide a list of the plants used, their time of harvest, mode of offering, and possible symbolism. Analysis of the temples' macrobotanical (seed and fruits) plant assemblage reveals the offerings; that the inception date for rites was early spring; and sheds light on the date of the final utilization of the temples (late summer/early fall). Besides food crops, we note the earliest cultic use of chaste tree (Vitex agnus-castus), crown daisy (Glebionis coronaria), and scabious (Lomelosia argentea). These wide-spread Mediterranean plants were known so far only in later cults-of early Greek deities, such as Hera, Artemis, Demeter, and Asclepios. We discuss the data as reflecting that the Philistine religion relied on the magic and power of nature, such as fresh water and seasonality, which influence human life, health, and activity. In sum, our results offer novel insights into the culture of the Philistines.

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.

Hypothyroidism in children with steroid-resistant nephrotic syndrome.

BACKGROUND: Non-autoimmune hypothyroidism has been reported in children with congenital nephrotic syndrome. The hypothyroid state was attributed to massive prolonged thyroid hormone loss. However, this endocrine abnormality has not been reported in steroid-resistant nephrotic syndrome (SRNS) despite similar long-standing proteinuria. METHOD: We describe all the patients with SRNS in our clinic's follow-up who developed non-autoimmune hypothyroidism. RESULTS: Five children aged 3-11 years at diagnosis of SRNS and followed for 5-42 months developed hypothyroidism (depressed free thyroxin and elevated thyrotropin levels) without evidence of autoimmune thyroiditis. The diagnosis of hypothyroidism was not temporarily related to disease duration or renal function. The disease was resistant to all therapies, renal function deteriorated in all the patients within 1.5-14.5 years from diagnosis. Despite thyroxine treatment and a decline in renal function, thyroid hormone level normalized only after reaching end stage renal disease (ESRD) and hemodialysis start. Nephrotic syndrome recurrence after kidney transplantation (in three patients with focal segmental glomerulosclerosis) was not accompanied by recurrent hypothyroidism. CONCLUSION: It is our impression that non-autoimmune hypothyroidism is a potential significant complication of SRNS, and should be actively sought for especially in cases with renal function deterioration. Hypothyroidism usually resolved when these patients reach ESRD. The incidence and pathogenesis of this condition require further study.

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.

Prenatal programming of rat thick ascending limb chloride transport by low-protein diet and dexamethasone.

Prenatal administration of dexamethasone and a low-protein diet has been shown to result in hypertension in the offspring when they are adults. The cause for the hypertension is unknown. The purpose of this study was to examine whether there was prenatal programming of thick ascending limb transport. Rats were administered either dexamethasone for 4 days (0.2 mg/kg body wt) by intraperitoneal injection daily between the 15th and 18th day of gestation, or they were fed a low-protein diet (6% protein) or an isocaloric normal protein diet (20% protein) from day 12 gestation until birth. The offspring were studied as adults. Prenatal dexamethasone and dietary protein deprivation resulted in an increase in blood pressure. Offspring of mothers fed a low-protein diet had an increase in medullary but not cortical bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) protein abundance (P < 0.01). There was not a statistically significant increase in medullary NKCC2 by prenatal dexamethasone (P = 0.07). Both prenatal administration of dexamethasone and a low-protein diet resulted in an increase in medullary thick ascending limb chloride transport compared with control (298 +/- 33 pmoles x mm(-1) x min(-1), 280 +/- 26 pmoles x mm(-1) x min(-1), and 191 +/- 21 pmoles x mm(-1) x min(-1), respectively P < 0.05). There was a higher lumen-positive transepithelial potential difference in the prenatal dexamethasone and low-protein group compared with control as well. Administration of furosemide for 24 h resulted in a decrease in blood pressure in the low-protein group but not the control group. This study demonstrates that insults administered to the fetus can program altered sodium transport. Increased tubular sodium transport is a likely cause for the hypertension by prenatal programming.

Long-term Outcome of 1-step Kidney Transplantation and Bladder Augmentation Procedure in Pediatric Patients.

BACKGROUND: Guidelines for bladder augmentation (BA) in kidney transplantation (KT) recipients are not well-defined. In our center, simultaneous BA with KT (BA-KT) is performed. We assessed transplantation outcomes of this unique extensive procedure. METHODS: A case-control single center retrospective study. Transplantation outcomes were compared with those of KT recipients who did not need BA. RESULTS: Compared with 22 patients who underwent KT only, for 9 who underwent BA-KT, surgical complications and the need for revision in the early posttransplantation period were similar; early graft function was better: estimated glomerular filtration rate, 96.5 ± 17.1 versus 79.4 ± 16.6 mL/min at 0 to 6 months (P = 0.02); posttransplantation clean intermittent catheterization was more often needed: by 78% (7/9) versus 13% (3/22); and asymptomatic bacteriuria was more common: 100% versus 9% during the first 6 months (P < 0.001), 55% versus 9% (P = 0.02) and 66.6% versus 9% during the first and second years, respectively (P = 0.004). Urinary tract infection (UTI) incidence was also higher: 100% versus 23% during the first 6 months and 44% versus 9% during the second year posttransplantation. Graft function deteriorated significantly in the BA-KT group by the fifth posttransplantation year: estimated glomerular filtration rate was 47.7 ± 39.7 mL/min versus 69 ± 21.3 mL/min, with only 6 (66%) of 9 functioning grafts versus 100% in the KT only group. Causes of graft loss were noncompliance with drug therapy in 2 patients and recurrent UTIs in 2 patients. CONCLUSIONS: Excellent short-term outcome for simultaneous BA-KT is threatened by graft loss due to a high prevalence of UTIs and patient noncompliance with the demanding complex posttransplantation therapy.