The Study of the Epidemiology of Pediatric Hypertension Registry (SUPERHERO): Rationale and Methods.

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders.

Acute kidney injury surveillance in the high-risk neonatal population following implementation of creatinine screening protocol.

AIM: Acute kidney injury (AKI) in neonates is associated with longer hospital stays and higher mortality rates. However, there is significant variability in prevalence rates of AKI and the true burden is incompletely understood. In November 2020, the University of Iowa Stead Family Children's Hospital Neonatal Intensive Care Unit implemented a creatinine screening protocol to enhance kidney function monitoring. We sought to evaluate adherence to the protocol to determine if increased surveillance led to increased detection of AKI events. METHODS: A retrospective chart review was conducted for neonates born at <30 weeks' gestation admitted between 2015 and 2020. We reviewed 100 charts in both the pre (2015-2016) and post (2020-2021) implementation era of the AKI surveillance protocol. AKI was defined according to neonatal modified KDIGO criteria. RESULTS: Following implementation of the protocol, neonates were significantly more likely to have creatinine checked (p < 0.001). Serum creatinine was drawn according to protocol guidelines 68% of the time, and 42% of patients (34/82) had an 80% or higher adherence to the protocol. There was a significant increase in detection of AKI in the post-protocol cohort (13/82, incidence of 16%) compared to the pre-protocol cohort (5/83, incidence of 6%), (p = 0.047). CONCLUSION: The implementation of a serum creatinine screening protocol increased the frequency of creatinine draws and detection of AKI.

Prospective Study of the Multisite Spread of a Medication Safety Intervention: Factors Common to Hospitals With Improved Outcomes.

Context and implementation approaches can impede the spread of patient safety interventions. The objective of this article is to characterize factors associated with improved outcomes among 9 hospitals implementing a medication safety intervention. Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a pharmacist-driven intervention that led to a sustained reduction in nephrotoxic medication-associated acute kidney injury (NTMx-AKI) at 1 hospital. Using qualitative comparative analysis, the team prospectively assessed the association between context and implementation factors and NTMx-AKI reduction during NINJA spread to 9 hospitals. Five hospitals reduced NTMx-AKI. These 5 had either (1) a pharmacist champion and >2 pharmacists working on NINJA (Scon 1.0, Scov 0.8) or (2) a nephrologist-implementing NINJA with minimal competing organizational priorities (Scon 1.0, Scov 0.2). Interviews identified ways NINJA team leaders obtained pharmacist support or successfully implemented without that support. In conclusion, these findings have implications for future spread of NINJA and suggest an approach to study spread of safety interventions more broadly.

Clinical and Histopathologic Characteristics of Pediatric Patients With Primary Membranous Nephropathy.

Introduction: Primary membranous nephropathy (PMN) is uncommon in children. Therefore, data on the clinical course of affected children are scarce. In recent years, several novel antigens have been implicated in the pathogenesis of PMN. However, the histopathologic characteristics of pediatric patients with PMN remain poorly represented in the literature. Methods: We have retrospectively analyzed the clinical presentation and outcomes data of 21 children with PMN from 3 centers in the United States. In addition, we have identified novel antigens in biopsy specimens from these patients and correlated their presence or absence to clinical outcomes. Finally, we compared the results of the novel antigen staining from our clinical cohort to a validation cohort of 127 biopsy specimens from children with PMN at Arkana Laboratories. Results: The data from the 2 cohorts demonstrated similar overall antigen positivity rates of 62% to 63%, with phospholipase A2 receptor (PLA2R) and exostosin 1 (EXT1) being the most commonly found antigens. Results from the clinical cohort showed that overall, the kidney prognosis for children with PMN was good, with 17 of 21 patients entering a complete or partial remission. Children who were positive for PLA2R or EXT1 were significantly more likely to enter remission than those in the antigen negative group. Conclusion: Approximately 60% of pediatric membranous cases are positive for a novel antigen on kidney biopsy and the clinical prognosis is generally favorable. More studies are needed to understand the clinical implications of each specific novel antigen.

NSAID-associated acute kidney injury in hospitalized children - a prospective Pediatric Nephrology Research Consortium study.

BACKGROUND: Acute kidney injury (AKI) in children has serious short-term and long-term consequences. We sought 1) to prospectively describe NSAID-associated AKI in hospitalized children; 2) to determine if NSAID-associated AKI was more severe in younger children < 5 years; and 3) to follow outcomes after hospitalization for NSAID-associated AKI. METHODS: This was a prospective, multi-center study in hospitalized children 1 month to 18 years. Parents/guardians were given a brief questionnaire to determine the dosing, duration, and type of NSAIDs given. Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria were used to stage AKI severity. Patients with other causes of AKI were excluded (e.g., other nephrotoxins, sepsis, malignancy, etc.). RESULTS: We identified 25 patients with NSAID-associated AKI, accounting for 3.1% of AKI. All 25 had AKI upon hospital presentation. The median age was 15.5 years, and 20/25 (80%) had volume depletion. Median duration of NSAID use was 2 days, and 63% of patients took the normal recommended NSAID dose. Median hospital length of stay was 4 days, and none required dialysis. At the most recent estimated glomerular filtration rate (eGFR) after discharge (available in 17/25 patients), only 4/17 (24%) had eGFR ≥ 90 ml/min/1.73 m2, and 13/17 (76%) had eGFR 60 to < 90 ml/min/1.73 m2, indicative of abnormal kidney function. CONCLUSIONS: NSAID-associated AKI usually occurs with recommended NSAID dosing in the setting of dehydration. Follow-up after AKI showed a substantial rate of CKD. Therefore, we recommend that NSAIDs should not be used in dehydrated children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Nephrotoxin Exposure and Acute Kidney Injury in Adults.

BACKGROUND: Rates of nephrotoxic AKI are not well described in adults due to lack of a clear definition, debate over which drugs should be considered nephrotoxins, and illness-related confounding. Nephrotoxic Injury Negated by Just-in Time Action (NINJA), a program that reduces rates of nephrotoxic AKI in pediatric populations, may be able to address these concerns, but whether NINJA can be effectively applied to adults remains unclear. METHODS: In this retrospective cohort study conducted at the University of Iowa Hospital, we included adult patients admitted to a general hospital floor for ≥48 hours during 2019. The NINJA algorithm screened charts for high nephrotoxin exposure and AKI. After propensity score matching, Cox proportional hazard modeling was used to evaluate the relationship between nephrotoxic exposure and all-stage AKI, stage 2-3 AKI, or death. Additional analyses evaluated the most frequent nephrotoxins used in this population. RESULTS: Of 11,311 patients, 1527 (16%) had ≥1 day of high nephrotoxin exposure. Patients with nephrotoxic exposures subsequently developed AKI in 29% of cases, and 22% of all inpatient AKI events met nephrotoxic AKI criteria. Common nephrotoxins were vancomycin, iodinated contrast dye, piperacillin-tazobactam, acyclovir, and lisinopril. After propensity score matching, Cox proportional hazard models for high nephrotoxin exposure were significantly associated with all AKI (hazard ratio [HR] 1.43, 1.19-1.72, P<0.001), stage 2-3 AKI (HR 1.78, 1.18-2.67, P=0.006), and mortality (HR 2.12, 1.09-4.11, P=0.03). CONCLUSIONS: Nephrotoxin exposure in adults is common and is significantly associated with AKI development, including stage 2-3 AKI.

Utility of the 2018 revised ISN/RPS thresholds for glomerular crescents in childhood-onset lupus nephritis: a Pediatric Nephrology Research Consortium study.

BACKGROUND: The revised 2018 ISN/RPS Classification System for lupus nephritis (LN) includes calculations for both activity index (A.I.) and chronicity index (C.I.). Unchanged were the thresholds of < 25%, 25-50%, and > 50% crescents to distinguish between mild, moderate, and severe activity/chronicity. We aimed to evaluate these thresholds for percent crescents in childhood-onset LN. METHODS: Eighty-six subjects < 21 years of age were enrolled from the Pediatric Glomerulonephritis with Crescents Registry, a retrospective multi-center cohort sponsored by the Pediatric Nephrology Research Consortium. Thresholds of 10%, 25%, and 50% for both cellular/fibrocellular and fibrous crescents were interrogated for primary outcomes of kidney failure, eGFR, and eGFR slope. RESULTS: Median age at time of initial biopsy was 14 years (range 1-21). Median follow-up time was 3 years (range 1-11). Cumulative incidence of kidney failure was 6% at 1 year and 10% at latest follow-up. Median eGFR slope was - 18 mL/1.73 m2/min (IQR - 51 to + 8) at 1 year and - 3 mL/min/1.73 m2/year (IQR - 19 to + 6) at latest follow-up. We found no difference in kidney failure at the proposed < 25% and 25-50% cellular crescents thresholds, and thus added a new provisional threshold of 10% that better predicted outcomes in children. Moreover, use of 10% and 25% thresholds for fibrous crescents showed a fourfold and sevenfold increase in risk of kidney failure. CONCLUSIONS: In children with crescentic LN, use of 10% and 25% thresholds for cellular crescents better reflects disease activity, while these thresholds for fibrous crescents better discriminates kidney disease outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Outcomes of granulocyte colony-stimulating factor use in pediatric kidney transplant recipients: A Pediatric Nephrology Research Consortium study.

BACKGROUND: Neutropenia is common in the first year after pediatric kidney transplant and is associated with an increased risk of infection, allograft loss, and death. Granulocyte colony-stimulating factor (G-CSF) increases neutrophil production, but its use in pediatric solid organ transplant recipients remains largely undescribed. METHODS: We performed a multicenter retrospective cohort study of children with neutropenia within the first 180 days after kidney transplant. Multivariable linear regression and Poisson regression were used to assess duration of neutropenia and incidence of hospitalization, infection, and rejection. RESULTS: Of 341 neutropenic patients, 83 received G-CSF during their first episode of neutropenia. Median dose of G-CSF was 5 mcg/kg for 3 (IQR 2-7) doses. G-CSF use was associated with transplant center, induction immunosuppression, steroid-free maintenance immunosuppression, hospitalization, and decreases in mycophenolate mofetil, valganciclovir, and trimethoprim-sulfamethoxazole dosing. Absolute neutrophil count nadir was also significantly lower among those treated with G-CSF. G-CSF use was not associated with a shorter duration of neutropenia (p = .313) and was associated with a higher rate of neutropenia relapse (p = .002) in adjusted analysis. G-CSF use was associated with a decreased risk of hospitalization (aIRR 0.25 (95%CI 0.12-0.53) p < .001) but there was no association with incidence of bacterial infection or rejection within 90 days of neutropenic episode. CONCLUSION: G-CSF use for neutropenia in pediatric kidney transplant recipients did not shorten the overall duration of neutropenia but was associated with lower risk of hospitalization. Prospective studies are needed to determine which patients may benefit from G-CSF treatment.

Multicenter data to improve health for pediatric renal transplant recipients in North America: Complementary approaches of NAPRTCS and IROC.

Kidney transplantation increases life expectancy and improves quality of life for children with end-stage kidney disease, yet sequelae of transplantation and treatment make it difficult for transplant recipients to enjoy health and quality of life similar to their healthy peers. The NAPRTCS network was among the first to use multicenter data to inform improvements in care and outcomes for children with a kidney transplant through observational research. Now, with new technologies and unprecedented access to data, it is possible to create learning health systems as envisioned by the US National Academy of Sciences to seamlessly integrate research and continuous improvement of clinical care. In this review, we present two pre-eminent North American networks focused on using multicenter data to drive improved care and outcomes for children with a kidney transplant. Whereas, for the past 30 years NAPRTCS has focused on discovery of best practices through observational research and clinical trials, the Improving Renal Outcomes Collaborative, established in 2016, engages patients, families, clinicians, and researchers in redesigning the healthcare delivery system to enable practice change and continuous improvement of health outcomes. We discuss the history and past contributions of these networks, as well as current activities, barriers, and potential future solutions to more fully realize the vision of a true learning health system for pediatric kidney transplant recipients.

Renal Survival in Children with Glomerulonephritis with Crescents: A Pediatric Nephrology Research Consortium Cohort Study.

There is no evidence-based definition for diagnosing crescentic glomerulonephritis. The prognostic implications of crescentic lesions on kidney biopsy have not been quantified. Our objective was to determine risk factors for end-stage kidney disease (ESKD) in patients with glomerulonephritis and crescents on kidney biopsy. A query of the Pediatric Nephrology Research Consortium's Pediatric Glomerulonephritis with Crescents registry identified 305 patients from 15 centers. A retrospective cohort study was performed with ESKD as the primary outcome. Median age at biopsy was 11 years (range 1-21). The percentage of crescents was 3-100% (median 20%). Etiologies included IgA nephropathy (23%), lupus (21%), IgA vasculitis (19%) and ANCA-associated GN (13%), post-infectious GN (5%), and anti-glomerular basement membrane disease (3%). The prevalence of ESKD was 12% at one year and 16% at last follow-up (median = 3 years, range 1-11). Median time to ESKD was 100 days. Risk factors for ESKD included %crescents, presence of fibrous crescents, estimated GFR, and hypertension at biopsy. For each 1% increase in %crescents, there was a 3% decrease in log odds of 1-year renal survival (p = 0.003) and a 2% decrease in log odds of renal survival at last follow-up (p < 0.001). These findings provide an evidence base for enrollment criteria for crescentic glomerulonephritis in future clinical trials.

The Improving Renal Outcomes Collaborative: Blood Pressure Measurement in Transplant Recipients.

BACKGROUND AND OBJECTIVES: Hypertension is highly prevalent in pediatric kidney transplant recipients and contributes to cardiovascular death and graft loss. Improper blood pressure (BP) measurement limits the ability to control hypertension in this population. Here, we report multicenter efforts from the Improving Renal Outcomes Collaborative (IROC) to standardize and improve appropriate BP measurement in transplant patients. METHODS: Seventeen centers participated in structured quality improvement activities facilitated by IROC, including formal training in quality improvement methods. The primary outcome measure was the proportion of transplant clinic visits with appropriate BP measurement according to published guidelines. Prospective data were analyzed over a 12-week pre-intervention period and a 20-week active intervention period for each center and then aggregated as of the program-specific start date. We used control charts to quantify improvements across IROC centers. We applied thematic analysis to identify patterns and common themes of successful interventions. RESULTS: We analyzed data from 5392 clinic visits. At baseline, BP was measured and documented appropriately at 11% of visits. Center-specific interventions for improving BP measurement included educating clinic staff, assigning specific team member roles, and creating BP tracking tools and alerts. Appropriate BP measurement improved throughout the 20-week active intervention period to 78% of visits. CONCLUSIONS: We standardized appropriate BP measurement across 17 pediatric transplant centers using the infrastructure of the IROC learning health system and substantially improved the rate of appropriate measurement over 20 weeks. Accurate BP assessment will allow further interventions to reduce complications of hypertension in pediatric kidney transplant recipients.

A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children.

Nephrotoxic medication (NTMx) exposure is a common cause of acute kidney injury (AKI) in hospitalized children. The Nephrotoxic Injury Negated by Just-in time Action (NINJA) program decreased NTMx associated AKI (NTMx-AKI) by 62% at one center. To further test the program, we incorporated NINJA across nine centers with the goal of reducing NTMx exposure and, consequently, AKI rates across these centers. NINJA screens all non-critically ill hospitalized patients for high NTMx exposure (over three medications on the same day or an intravenous aminoglycoside over three consecutive days), and then recommends obtaining a daily serum creatinine level in exposed patients for the duration of, and two days after, exposure ending. Additionally, substitution of equally efficacious but less nephrotoxic medications for exposed patients starting the day of exposure was recommended when possible. The main outcome was AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria (increase of 50% or 0.3 mg/dl over baseline). The primary outcome measure was AKI episodes per 1000 patient-days. Improvement was defined by statistical process control methodology and confirmed by Autoregressive Integrated Moving Average (ARIMA) modeling. Eight consecutive bi-weekly measure rates in the same direction from the established baseline qualified as special cause change for special process control. We observed a significant and sustained 23.8% decrease in NTMx-AKI rates by statistical process control analysis and by ARIMA modeling; similar to those of the pilot single center. Thus, we have successfully applied the NINJA program to multiple pediatric institutions yielding decreased AKI rates.

Renal Replacement Therapy in Neonates.

Acute kidney injury (AKI) is a highly prevalent disease entity in the NICU, affecting nearly one-quarter of critically ill neonates by some reports. Though medical management remains the mainstay in the treatment of AKI, renal replacement therapy (RRT) is indicated when conservative measures are unable to maintain electrolytes, fluid balance, toxins, or waste products within a safe margin. Several modalities of RRT exist for use in neonatal populations, including peritoneal dialysis, hemodialysis, and continuous RRT. It is the aim of this review to introduce each of these RRT modalities, as well as to discuss their technical considerations, benefits, indications, contraindications, and complications.

Evidence-based development of a nephrotoxic medication list to screen for acute kidney injury risk in hospitalized children.

PURPOSE: Medications are commonly associated with acute kidney injury (AKI). However, in both clinical practice and research, consideration of specific medications as nephrotoxic varies widely. The Nephrotoxic Injury Negated by Just-in-time Action quality improvement collaborative was formed to focus on prevention or reduction of nephrotoxic medication-associated AKI in noncritically ill hospitalized children. However, there were discrepancies among institutions as to which medications should be considered nephrotoxic. The collaborative convened a Nephrotoxic Medication (NTMx) Subcommittee to develop a consensus for the classification of nephrotoxic medications. SUMMARY: The NTMx Subcommittee initially included pediatric nephrologists, a pharmacist, and a pediatric intensivist. The committee reviewed NTMx lists from the collaborative and identified changes from the initial NTMx list. The NTMx Subcommittee conducted a literature review of the disputed medications and assigned an evidence grade based on the reported association with nephrotoxicity and the quality of the data. The association between medication exposure and AKI was also determined using administrative data from the Pediatric Health Information Systems database. The NTMx Subcommittee then came to a majority consensus regarding which medications should be included on the list. The subcommittee's recommendations were presented to the larger collaborative for approval, and consensus was achieved. The list continues to be reviewed and updated annually. CONCLUSION: Formation of a multicenter quality-improvement initiative exposed current limitations as to which medications are considered nephrotoxic in clinical and research settings and presented an opportunity to approach this problem using an evidence-based process. A consensus definition of nephrotoxic-medication exposure was achieved.

Diagnosis, Treatment, and Outcomes in Children With Congenital Nephrogenic Diabetes Insipidus: A Pediatric Nephrology Research Consortium Study.

Background and Objectives: Congenital or primary nephrogenic diabetes insipidus (NDI) is a rare genetic disorder that severely impairs renal concentrating ability, resulting in massive polyuria. There is limited information about prognosis or evidence guiding the management of these patients, either in the high-risk period after diagnosis, or long-term. We describe the clinical presentation, genetic etiology, treatment and renal outcomes in a large group of children <21 years with NDI. Design: A multi-center retrospective chart review. Results: We report on 66 subjects from 16 centers. They were mainly male (89%) and white (67%). Median age at diagnosis was 4.2 months interquartile range (IQR 1.1, 9.8). A desmopressin acetate loading test was administered to 46% of children at a median age of 4.8 months (IQR 2.8, 7.6); only 15% had a water restriction test. Genetic testing or a known family history was present in 70% of the patients; out of those genetically tested, 89 and 11% had mutations in AVPR2 and AQP2, respectively. No positive family history or genetic testing was available for 30%. The most common treatments were thiazide diuretics (74%), potassium-sparing diuretics (67%) and non-steroidal anti-inflammatory drugs (42%). At the time of first treatment, 70 and 71% of children were below -2 standard deviations (SD) for weight and height, respectively. At last follow-up, median age was 72.3 months (IQR 40.9, 137.2) and the percentage below -2 SD improved to 29% and 38% for weight and height, respectively. Adverse outcomes included inpatient hospitalizations (61%), urologic complications (37%), and chronic kidney disease (CKD) stage 2 or higher in 23%. Conclusion: We found the majority of patients were treated with thiazides with either a potassium sparing diuretic and/or NSAIDs. Hospitalizations, urologic complications, short stature, and CKD were common. Prospective trials to evaluate different treatment strategies are needed to attempt to improve outcomes.

Immunogenicity of Augmented Compared With Standard Dose Hepatitis B Vaccine in Pediatric Patients on Dialysis: a Midwest Pediatric Nephrology Consortium Study.

BACKGROUND AND OBJECTIVES: Patients on maintenance dialysis have a higher risk of unresponsiveness to hepatitis B vaccination and loss of hepatitis B immunity. Adult guidelines recommend augmented dosing (40 mcg/dose), resulting in improved response in adults. We sought to determine whether children on dialysis mount a similar antibody response when given standard or augmented dosing of hepatitis B vaccine. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective review of patients on dialysis aged <19 years from May 1, 2008 to May 1, 2013 at 12 pediatric dialysis units. Hepatitis B surface antibody (HBsAb) titers ≥10 mIU/ml were defined as protective. RESULTS: A total of 187 out of 417 patients received one or more hepatitis B vaccine boosters. The median age was 13 years; the cohort was 57% boys and 59% white. Booster dose or HBsAb titers were missing in 17 patients. Conversion to protective HBsAb titers was achieved in 135 out of 170 patients (79%) after their first single-dose booster or multidose booster series. In patients receiving a single-dose booster, the response rate was 53% (nine out of 17) after a 10 mcg dose, 86% (65 out of 76) after a 20 mcg dose, and 65% (17 out of 26) after a 40 mcg hepatitis B vaccine dose. In patients receiving a multidose booster series, the response rate was 95% (19 out of 20) after a 10 mcg/dose series, 83% (20 out of 24) after a 20 mcg/dose series, and 71% (five out of seven) after a 40 mcg/dose series. Patients receiving a multidose booster series had a response rate of 86% (44 out of 51), compared with 76% (91 out of 119) in patients receiving a single-dose booster (P=0.21). Twenty-seven patients received more than one single-dose booster or multidose series, and 26 out of 27 (96%) eventually gained immunity after receiving one to three additional single-dose boosters or multidose booster series. CONCLUSIONS: There was no clear gradient of increasing seroconversion rate with increasing vaccine dose in this cohort of pediatric patients on dialysis.

Bortezomib in the treatment of antibody-mediated rejection in pediatric kidney transplant recipients: A multicenter Midwest Pediatric Nephrology Consortium study.

Antibody-mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody-mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven antibody-mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty-three patients received bortezomib for antibody-mediated rejection at nine pediatric kidney transplant centers. Ninety percent of patients received intravenous immunoglobulin, 78% received plasmapheresis, and 78% received rituximab. After a median follow-up of 15 months, 65% of patients had a functioning graft. The estimated glomerular filtration rate improved or stabilized in 61% and 36% of patients at 3 and 12 months post-bortezomib, respectively. The estimated glomerular filtration rate at diagnosis significantly predicted estimated glomerular filtration rate at 12 months after adjusting for chronic histologic changes (P .001). Fifty-six percent of patients showed an at least 25% reduction in the mean fluorescence intensity of the immune-dominant donor-specific antibody, 1-3 months after the first dose of bortezomib. Non-life-threatening side effects were documented in 21 of 33 patients. Pediatric kidney transplant recipients tolerated bortezomib without life-threatening side effects. Bortezomib may stabilize estimated glomerular filtration rate for 3-6 months in pediatric kidney transplant recipients with antibody-mediated rejection.

Chronic kidney disease in the neonate: etiologies, management, and outcomes.

Neonatal chronic kidney disease (CKD) occurs with an estimated incidence of 1 in 10,000 live births, whereas the incidence of neonatal end-stage renal disease (ESRD) is about 7.1 per million age-related population. The most frequent etiologies are renal hypoplasia/dysplasia, posterior urethral valves, and other congenital anomalies of the kidney and urinary tract. Other etiologies include polycystic kidney disease, cortical necrosis, and renal vascular thrombosis. Management of CKD focuses primarily on replacing renal functions such as erythropoietin, 1,25-hydroxylation of vitamin D, electrolyte homeostasis/excretion, and, in ESRD, waste product removal. Nutrition and growth monitoring are of utmost importance, with the majority of ESRD infants requiring gastrostomy tube for nutrition. Outcomes of neonates (<31 days) started on dialysis continue to improve, with large cohort studies showing 2-3-year survival rates of 79-81%. As in other neonatal disciplines, the gestational age and size limits for safe provision of dialysis continue to decrease.