Vancomycin Dosing and Its Association With Acute Kidney Injury in Pediatric Cardiac Intensive Care Patients Under 3 Months of Age.

BACKGROUND: The standard vancomycin regimen for term neonates is 45 mg/kg/day. However, the optimal starting vancomycin dosing for achieving therapeutic levels in young infants in cardiac intensive care units remains unknown. Moreover, data on the association of supratherapeutic vancomycin levels with acute kidney injury (AKI) are limited. METHODS: Retrospective study of infants ≤3 months old, receiving vancomycin following congenital heart surgery at postoperative intensive care unit admission. Assessed were vancomycin dosing, achievement of therapeutic trough concentration of 10-20 mg/L and development of AKI, based on the modified Kidney Disease Improving Global Outcomes criteria. RESULTS: Inclusion criteria were met by 109 patients with a median age of 8 days (IQR: 6-16). The mean (SD) vancomycin dose required for achieving therapeutic concentration was 28.9 (9.1) mg/kg at the first postoperative day. Multivariate logistic regression identified higher preoperative creatinine levels and shorter cardiopulmonary bypass time as predictors of supratherapeutic vancomycin concentrations (c-index 0.788). During the treatment course, 62 (56.9%) developed AKI. Length of stay and mortality were higher in those who developed AKI as compared with those who did not. Multivariate logistic regression identified higher vancomycin concentration as a predictor for postoperative AKI, OR, 3.391 (95% CI: 1.257-9.151), P = 0.016 (c-index 0.896). CONCLUSION: Our results support a lower starting vancomycin dose of ~30 mg/kg/day followed by an early personalized therapeutic approach, to achieve therapeutic trough concentrations of 10-20 mg/L in cardiac postoperative term infants. Supratherapeutic concentrations are associated with an increased risk for AKI, which is prevalent in this population and associated with adverse outcomes.

Clinical profile of re-hospitalizations in pediatric kidney and liver transplant recipients.

BACKGROUND: Solid organ transplantation has evolved in recent decades, resulting in a rise in patient and graft survival. Frequent hospitalizations affect graft function, patients' health, and quality of life. This study characterizes the frequency and causes of post-transplant hospitalizations among pediatric recipients. METHODS: This is a retrospective observational study evaluating pediatric kidney transplant recipients (KTR) and liver transplant recipients (LTR) aged 0-21 years, followed at a tertiary pediatric center in Israel from 2012 to 2017. Data were collected starting at 60 days post-transplantation. Diagnoses of admissions were based on clinical, laboratory, and radiographic findings. RESULTS: Forty-nine KTR experienced 199 all-cause re-hospitalizations (median number of re-hospitalizations per patient - 3 (IQR [interquartile range] 1-5.5), while 351 re-hospitalizations were recorded in 56 LTR (median - 5 [IQR 2-8.8]). Median follow-up time was 2.2 years for KTR (IQR 1-3.9) and 3 years for LTR (IQR 2.1-4.1). The most common cause for hospitalization for both cohorts was infection (50.8% and 62%, respectively). Gram-negative bacteria were the most common pathogens identified in KTR, while viral pathogens were more common in LTR (51% and 57% of pathogen-identified cases, respectively). CONCLUSIONS: This is the largest study to describe rehospitalizations for pediatric solid organ recipients. The hospital admission rate was higher in LTR in comparison to KTR. Infections were the most common cause of hospitalization throughout the whole study period in both populations. Frequent hospitalizations impose a heavy burden on patients and their families; better understanding of hospitalization causes may help to minimize their frequency.

Diagnostic Utility of Exome Sequencing Among Israeli Children With Kidney Failure.

Introduction: Genetic etiologies are estimated to account for a large portion of chronic kidney diseases (CKD) in children. However, data are lacking regarding the true prevalence of monogenic etiologies stemming from an unselected population screen of children with advanced CKD. Methods: We conducted a national multicenter prospective study of all Israeli pediatric dialysis units to provide comprehensive "real-world" evidence for the genetic basis of childhood kidney failure in Israel. We performed exome sequencing and assessed the genetic diagnostic yield. Results: Between 2019 and 2022, we recruited approximately 88% (n = 79) of the children on dialysis from all 6 Israeli pediatric dialysis units. We identified genetic etiologies in 36 of 79 (45%) participants. The most common subgroup of diagnostic variants was in congenital anomalies of the kidney and urinary tract causing genes (e.g., EYA1, HNF1B, PAX2, COL4A1, and NFIA) which together explain 28% of all monogenic etiologies. This was followed by mutations in genes causing renal cystic ciliopathies (e.g., NPHP1, NPHP4, PKHD1, and BBS9), steroid-resistant nephrotic syndrome (e.g., LAGE3, NPHS1, NPHS2, LMX1B, and SMARCAL1) and tubulopathies (e.g., CTNS and AQP2). The genetic diagnostic yield was higher among Arabs compared to Jewish individuals (55% vs. 29%) and in children from consanguineous compared to nonconsanguineous families (63% vs. 29%). In 5 participants (14%) with genetic diagnoses, the molecular diagnosis did not correspond with the pre-exome diagnosis. Genetic diagnosis has a potential influence on clinical management in 27 of 36 participants (75%). Conclusion: Exome sequencing in an unbiased Israeli nationwide dialysis-treated kidney failure pediatric cohort resulted in a genetic diagnostic yield of 45% and can often affect clinical decision making.

Adaptive immune response to BNT162b2 mRNA vaccine in immunocompromised adolescent patients.

Protective immunity against COVID-19 is orchestrated by an intricate network of innate and adaptive anti-viral immune responses. Several vaccines have been rapidly developed to combat the destructive effects of COVID-19, which initiate an immunological cascade that results in the generation of neutralizing antibodies and effector T cells towards the SARS-CoV-2 spike protein. Developing optimal vaccine-induced anti-SARS- CoV-2 protective immunity depends on a fully competent immune response. Some evidence was gathered on the effects of vaccination outcomes in immunocompromised adult individuals. Nonetheless, protective immunity elicited by the Pfizer Biontech BNT162b2 vaccine in immunocompromised adolescents received less attention and was mainly focused on the antibody response and their neutralization potential. The overall immune response, including T-cell activities, was largely understudied. In this study, we characterized the immune response of vaccinated immunocompromised adolescents. We found that immunocompromised adolescents, which may fail to elicit a humoral response and develop antibodies, may still develop cellular T-cell immunity towards SARS-CoV-2 infections. Furthermore, most immunocompromised adolescents due to genetic disorders or drugs (Kidney and liver transplantation) still develop either humoral, cellular or both arms of immunity towards SARS-CoV-2 infections. We also demonstrate that most patients could mount a cellular or humoral response even after six months post 2nd vaccination. The findings that adolescents immunocompromised patients respond to some extent to vaccination are promising. Finally, they question the necessity for additional vaccination boosting regimens for this population who are not at high risk for severe disease, without further testing of their post-vaccination immune status.

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.

Blood pressure monitoring following kidney transplantation in children: a comparison of invasive and noninvasive measurements using Doppler as a benchmark technique.

BACKGROUND: Blood pressure (BP) monitoring following pediatric kidney transplantation is essential for optimizing graft perfusion. Differences between invasive BP and noninvasive BP (NIBP) measurements are sometimes considerable. We aimed to assess agreement between invasive BP and NIBP in pediatric patients after kidney transplantation and compare with measurements obtained by systolic Doppler with manual sphygmomanometer as a reference technique. METHODS: A prospective, observational cohort study, of children aged 18 years or younger, admitted immediately following kidney transplantation to the pediatric intensive care unit of a tertiary, university-affiliated medical center, between May 2019 and June 2021. RESULTS: Eighty-two paired simultaneous measurements of invasive BP, NIBP, and Doppler BP in 18 patients were compared. Patients were significantly hypertensive, with mean systolic NIBP above the 95th percentile (96 ± 6%). Systolic invasive BP measurements were significantly higher than NIBP (149 ± 20 vs. 136 ± 15 mmHg, p < 0.001). Substantial differences (≥ 20 mmHg) were found in 23% (95% CI 15-34%). Similar disagreement was found between systolic invasive and Doppler BP (150 ± 23 and 137 ± 17 mmHg, respectively, p < 0.001). In contrast, systolic NIBP was in good agreement with Doppler BP (135 ± 17 and 138 ± 18, respectively, p = 0.27). A moderate to strong correlation was found between higher systolic invasive BP and the difference to systolic Doppler BP (Spearman's ρ = 0.63, p < 0.001). CONCLUSIONS: In children immediately following kidney transplantation, clinically significant disagreement was found between invasive and noninvasive BP measurements. Invasive BP values were significantly higher than those obtained by Doppler. Better agreement was found between NIBP and Doppler. These issues should be considered when interpreting BP measurements in this sensitive patient population. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

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.

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.

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.

[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.

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.

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.

Peri-transplant aminophylline in pediatric kidney transplant recipients of donation after brain death: a double-blinded placebo-controlled randomized clinical trial.

BACKGROUND: During kidney transplantation, the transplanted kidney undergoes ischemia reperfusion injury, with adenosine being a major mediator. This study aimed to assess whether aminophylline, an adenosine receptor antagonist, improves early graft function and reduces incidence of delayed graft function (DGF) and slow graft function (SGF). METHODS: Single center, double-blinded, placebo-controlled randomized clinical trial. Pediatric patients admitted for renal transplantation from donation after brain death donors were randomized into a treatment arm receiving aminophylline and a placebo arm receiving normal saline infusions. Primary outcome was estimated glomerular filtration rate (eGFR) at 5 days post-transplant. Secondary outcomes were rates of DGF/SGF and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels. RESULTS: Twenty-three patients were randomized to aminophylline and 27 to placebo. There was no difference in day 5 eGFR, rate of DGF/SGF, or urine NGAL/Creatinine level between aminophylline vs. placebo arm (eGFR 67.39 ± 38.9 ml/min/1.73m2 vs. 80.48 ± 52.1 ml/min/1.73m2p = 0.32; DGF/SGF 5/23 (21.7%) vs. 3/27 (11.1%) p = 0.31; urine NGAL/creatinine 300.5 ng/mg IQR 105.5-1464.5 ng/mg vs. 425.4 ng/mg IQR 140.3-1126.2 ng/mg, p = 0.95; respectively). At 12 months, there was 100% patient survival and 98% graft survival. eGFR at 12 months was similar between the two arms. CONCLUSIONS: There was no benefit in peri-transplant aminophylline administration. Our results are limited by small sample size, since sample calculations were based on primary outcome of day 5 eGFR and low rate of DGF/SGF, which may have precluded us from demonstrating efficacy. Further clinical studies are necessary to determine any benefit of aminophylline in kidney transplant recipients, particularly from high-risk donors.

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.

Is eculizumab indicated in patients with atypical hemolytic uremic syndrome already on prolonged dialysis? A case report and review of the literature.

BACKGROUND: Eculizumab has caused a revolution in the treatment and prognosis of atypical hemolytic uremic syndrome. Early initiation of treatment is recommended to increase chances of renal recovery. CASE-DIAGNOSIS/TREATMENT: We describe a boy with atypical hemolytic uremic syndrome who started eculizumab therapy after being on dialysis for 4.5 months, with complete anuria. With treatment, he was weaned off dialysis. CONCLUSION: We review the evidence in the literature and discuss the possible mechanism by which eculizumab induces renal recovery even in patients already on prolonged dialysis. This case report highlights the importance of a treatment trial with eculizumab, even in patients already on prolonged dialysis.

Prevalence of acute kidney injury after liver transplantation in children: Comparison of the pRIFLE, AKIN, and KDIGO criteria using corrected serum creatinine.

PURPOSE: To compare the application of three standardized definitions of acute kidney injury (AKI), using corrected serum creatinine values, in children immediately after liver transplantation. METHODS: Retrospective search of a tertiary pediatric hospital database yielded 77 patients (age < 18 years) who underwent liver transplantation in 2007-2017. Serum creatinine levels during the 24 h before and after surgery were corrected to daily fluid balance, and the prevalence of AKI was calculated using the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: AKI occurred in 44 children (57%) according to the pRIFLE criteria (stage I, 34%; stage II, 10%, stage III, 13%) and 33 children (43%) according to the AKIN and KDIGO criteria (stage I, 20%; stage II, 10%; stage III, 13%). There was a good correlation (kappa = 0.78) among the three criteria. AKI was associated with longer duration of mechanical ventilation (5.5 ±â€¯6.2 vs 3.6 ±â€¯4.0 days, p < .05) and longer ICU stay (15.2 ±â€¯8.8 vs 12.1 ±â€¯7.5 days, p < .05). Serum creatinine normalized in all patients (mean, 0.43 ±â€¯0.17 mg/dl) by one year. CONCLUSIONS: There is a good correlation among the three criteria defining AKI in pediatric liver transplant recipients. AKI is highly prevalent in this patient group and confers a worse ICU course.

Response to erythropoietin in pediatric patients with chronic kidney disease: insights from an in vitro bioassay.

BACKGROUND: Decreased production of erythropoietin (EPO) is a major cause of anemia associated with chronic kidney disease (CKD). Treatment with recombinant human EPO (rHuEPO) improves patients' quality of life and survival; however, there is a marked variability in response to rHuEPO. At present, no available laboratory test is capable of evaluating responsiveness to EPO treatment. The aim of the present study was to use an in vitro bioassay to estimate the effect of uremic environment on EPO-dependent erythroid cell proliferation. METHODS: EPO-dependent human erythroleukemia cells (UT-7) were incubated with exogenous EPO (2 u/ml) and sera obtained from 60 pediatric patients (aged 1-23 years). Three groups were studied: (1) 12 children on dialysis (4 peritoneal, 8 hemodialysis); (2) 28 patients with CKD 1-5 (not on dialysis), and (3) 20 healthy children. RESULTS: Sera from dialysis patients inhibited UT-7 cell growth compared to the CKD group and healthy controls at 48 h (p = 0.003 and p = 0.04, respectively) and 72 h of culture (p = 0.02 and p = 0.07, respectively). In 18 patients treated with rHuEPO, a significant inverse correlation was found between the EPO resistance index and cell proliferation at 48 h (p = 0.007, r = - 0.63) and 72 h (p = 0.03, r = - 0.52). CONCLUSIONS: Our findings support the presence of erythropoiesis inhibitory substances in uremic sera. EPO/EPO-R-dependent mechanisms may play a role in inhibiting erythropoiesis. The in vitro bioassay described herein may serve as an indicator of rHuEPO responsiveness which may encourage further investigation of underlying mechanisms of EPO resistance.

A novel outpatient desensitization protocol for recombinant human erythropoietin allergy in a pediatric patient.

BACKGROUND: Recombinant human erythropoietin, such as epoetin alfa and darbepoetin alfa, is an important therapy for anemia due to chronic renal failure. Allergy to recombinant human erythropoietin and the need for desensitization are rare. CASE PRESENTATION: We report here a novel epoetin alfa outpatient desensitization protocol in a girl who developed delayed cutaneous hypersensitivity to subcutaneous epoetin alfa and intravenous darbepoetin alfa. An initial attempt at traditional epoetin alfa desensitization failed, so we created a slower 17-day outpatient desensitization that succeeded and allowed treatment continuation. CONCLUSIONS: This case highlights the notion that delayed-type hypersensitivity to recombinant human erythropoietin can occur as evident by reproducible reactions after repeated exposures and slow outpatient desensitization can be considered when a trial of more rapid induction of tolerance is unsuccessful.