Longitudinal analysis of blood pressure and lipids in childhood nephrotic syndrome.

BACKGROUND: In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response. METHODS: A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia. RESULTS: Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time. CONCLUSIONS: Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment.

Thrombotic microangiopathy in children.

The syndrome of thrombotic microangiopathy (TMA) is a clinical-pathological entity characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ involvement. It comprises a spectrum of underlying etiologies that may differ in children and adults. In children, apart from ruling out shigatoxin-associated hemolytic uremic syndrome (HUS) and other infection-associated TMA like Streptococcus pneumoniae-HUS, rare inherited causes including complement-associated HUS, cobalamin defects, and mutations in diacylglycerol kinase epsilon gene must be investigated. TMA should also be considered in the setting of solid organ or hematopoietic stem cell transplantation. In this review, acquired and inherited causes of TMA are described with a focus on particularities of the main causes of TMA in children. A pragmatic approach that may help the clinician tailor evaluation and management is provided. The described approach will allow for early initiation of treatment while waiting for the definitive diagnosis of the underlying TMA.

Determinants of medication adherence in childhood nephrotic syndrome and associations of adherence with clinical outcomes.

BACKGROUND: Pediatric patients with nephrotic syndrome take medications long-term with significant toxicity and complex regimens, yet data on medication adherence are limited. METHODS: In a multicenter observational study of patients with nephrotic syndrome, NEPTUNE (NCT01209000), we surveyed caregivers of patients <19 years old and adolescent patients on medication adherence during longitudinal follow-up beginning in June 2015. Data extraction was in October 2020. We described the proportion of nonadherent patients at first survey. Participant social and economic factors, condition-related factors, therapy-related factors, and patient-related factors were examined for relationships with nonadherence by generalized linear mixed models using the longitudinal data. In exploratory fashion, we assessed the relationship between adherence and subsequent steroid response classification by binary logistic regression and adherence with healthcare utilization by Poisson regression. RESULTS: A total of 225 participants completed a median of 3 surveys during follow-up (IQR, 2-5), with a total of 743 surveys. Overall, 80 (36%) reported nonadherence with medications. In adjusted analysis, older age (per 1 year; OR 1.08; 95% CI, 1.03 1.12), lower maternal educational level (≥ high school vs. < high school; OR 0.47; 95% CI 0.25 to 0.89), and increased parent and self-identification of medications barriers (per 1 point; OR 1.57; 95% CI, 1.15-2.15) were significantly associated with nonadherence. No relationship between nonadherence and subsequent frequency of healthcare utilization was observed. A trend toward increased subsequent steroid resistance classification was seen with nonadherence, though not statistically significant. CONCLUSIONS: Medication nonadherence is common in pediatric nephrotic syndrome. Investigations into the use of surveys in the clinic setting to identify at-risk patients and ways to support families over time are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Eculizumab exposure in children and young adults: indications, practice patterns, and outcomes-a Pediatric Nephrology Research Consortium study.

BACKGROUND: Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and outcomes of a cohort of pediatric patients exposed to eculizumab. METHODS: A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients < 25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data. RESULTS: A total of 152 patients were identified, mean age 9.1 (+/-6.8) years. Eculizumab was used "off-label" in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing Escherichia coli HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy. CONCLUSIONS: This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.

Semaphorin 3B-associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients.

Membranous nephropathy results from subepithelial antigen-antibody complex deposition along the glomerular basement membrane. Although PLA2R, THSD7A, and NELL-1 account for a majority (about 80%) of the target antigens, the target antigen in the remaining cases is not known. Using laser microdissection of PLA2R-negative glomeruli of patients with membranous nephropathy followed by mass spectrometry we identified a unique protein, Semaphorin 3B, in three cases. Mass spectrometry failed to detect Semaphorin-3B in 23 PLA2R-associated cases of membranous nephropathy and 88 controls. Semaphorin 3B in all three cases was localized to granular deposits along the glomerular basement membrane by immunohistochemistry. Next, an additional eight cases of Semaphorin 3B-associated membranous nephropathy were identified in three validation cohorts by immunofluorescence microscopy. In four of 11 cases, kidney biopsy also showed tubular basement membrane deposits of IgG on frozen sections. Confocal microscopy showed that both IgG and Semaphorin 3B co-localized to the glomerular basement membrane. Western blot analysis of five available sera showed reactivity to reduced Semaphorin 3B in four of four patients with active disease and no reactivity in one patient in clinical remission; there was also no reactivity in control sera. Eight of the 11 cases of Semaphorin 3B-associated membranous nephropathy were pediatric cases. Furthermore, in five cases, the disease started at or below the age of two. Thus, Semaphorin 3B-associated membranous nephropathy appears to be a distinct type of disease; more likely to be present in pediatric patients.

Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) results in hypercoagulability and increased risk of infection. Furthermore, infection increases the risk of venous thromboembolism (VTE). Our objective was to determine the prevalence of infection, VTE, and the associated outcomes among a cohort of hospitalized children with NS. METHODS: All children with NS admitted to 17 pediatric hospitals across North America from 2010 to 2012 were included. Prevalence of infection and VTE was determined. Wilcoxon rank-sum and logistic regression were performed. RESULTS: Seven-hundred thirty hospitalizations occurred among 370 children with NS. One-hundred forty-eight children (40%) had ≥ 1 infection (211 episodes) and 11 (3%) had VTE. Those with VTE had infection more frequently (p = 0.046) and were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008). The most common infectious pathogen identified was Streptococcus pneumoniae. The median hospital length of stay for those with infection [10 vs 5 days (p < 0.0001)] or VTE [22 vs 6 days (p < 0.0001)] was longer than those without either complication. Of those with infection, 13% had an intensive care unit (ICU) stay compared with 3.3% of those without infection. Median ICU stay was 4 days in those with VTE compared to 0 days in those without (p < 0.001). By logistic regression, only the number of ICU days was associated with VTE (OR 1.074, 95% CI 1.013-1.138). CONCLUSIONS: Hospitalized children with NS have high rates of infection. Presence of VTE was associated with infection. Both were associated with longer hospitalizations and ICU stays.

Postcontrast Acute Kidney Injury in Pediatric Patients: A Cohort Study.

RATIONAL & OBJECTIVE: The risks of iodinated contrast material administered to pediatric patients are not well defined. The purpose of this study was to examine the rates of postcontrast acute kidney injury (AKI), dialysis therapy, and death following administration of intravenous contrast material to pediatric patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Pediatric (aged <18 years) patients who underwent either contrast-enhanced (contrast group) or unenhanced (noncontrast group) computed tomography (CT) at our institution from December 2001 to January 2016. EXPOSURE: Intravenous iodinated contrast material. OUTCOMES: Postcontrast AKI based on serum creatinine-defined KDIGO criteria, dialysis therapy, and death. ANALYTICAL APPROACH: Risks for AKI, dialysis therapy, and death were compared between contrast and noncontrast group patients using a propensity score analysis incorporating clinical covariates related to contrast exposure. RESULTS: 2,201 pediatric patients (1,773 contrast and 428 noncontrast) were identified. Rates of AKI and dialysis therapy in the contrast group were 3.3% (59/1,773) and 0.1% (2/1,773), respectively. Following propensity score adjustment, no differences in risk for AKI (stage 1 AKI: OR, 0.75 [95% CI, 0.32-1.78], P=0.5; stage 2: OR, 2.00 [95% CI, 0.18-21.9], P=0.6; stage 3: OR, 0.50 [95% CI, 0.05-5.48], P=0.6), dialysis therapy (OR, 1.00 [95% CI, 0.06-15.9], P=0.9), or death (OR, 1.50 [95% CI, 0.53-4.22], P=0.4) were observed between the contrast and noncontrast groups. All patients with post-CT stage 3 AKI diagnosed also had contrast-independent potential causes of AKI. LIMITATIONS: The study's small sample size and low rates of postcontrast AKI, dialysis therapy, and death limited the ability to detect an effect of contrast administration on these outcomes. Unmeasured residual confounders may limit the validity of our results. Few patients had decreased kidney function at the time of CT. CONCLUSIONS: Rates of postcontrast AKI, dialysis therapy, and death following contrast-enhanced CT were very low in this pediatric cohort. Although not detectably different, an effect of contrast on these outcomes could not be ruled out.

Discontinuation of dialysis with eculizumab therapy in a pediatric patient with dense deposit disease.

BACKGROUND: Dense deposit disease (DDD) is a rare glomerular disease caused by an uncontrolled activation of the alternative complement pathway leading to end-stage renal disease in 50 % of patients. As such, DDD has been classified within the spectrum of complement component 3 (C3) glomerulopathies due to its pathogenesis from alternative pathway dysregulation. Conventional immunosuppressive therapies have no proven effectiveness. Eculizumab, a terminal complement inhibitor, has been reported to mitigate disease in some cases. CASE-DIAGNOSIS/TREATMENT: We report on the efficacy of eculizumab in a pediatric patient who failed to respond to cyclophosphamide, corticosteroids, and plasma exchange. Complement biomarker profiling was remarkable for low serum C3, low properdin, and elevated soluble C5b-9. Consistent with these findings, the alternative pathway functional assay was abnormally low, indicative of alternative pathway activity, although neither C3-nephritic factors nor Factor H autoantibodies were detected. Eculizumab therapy was associated with significant improvement in proteinuria and renal function allowing discontinuation of hemodialysis (HD). Repeat C3 and soluble C5b-9 levels normalized, showing that terminal complement pathway activity was successfully blocked while the patient was receiving eculizumab therapy. Repeat testing for alternative pathway activation allowed for a successful decrease in eculizumab dosing. CONCLUSIONS: The case reported here demonstrates the successful recovery of renal function in a pediatric patient on HD following the use of eculizumab.

Membranous nephropathy associated with angiomatoid fibrous histiocytoma in a pediatric patient.

BACKGROUND: Though membranous nephropathy is a much more common cause of nephrotic syndrome in the adult population, it accounts for only a small fraction of cases in pediatrics. CASE-DIAGNOSIS/TREATMENT: We report a case of a 16-year-old boy with nephrotic syndrome due to membranous nephropathy in the setting of a rare tumor, angiomatoid fibrous histiocytoma. This patient's nephrotic-range proteinuria completely resolved following resection of this tumor. Angiomatoid fibrous histiocytoma, while known to cause other paraneoplastic syndromes such as anemia, has never been reported to cause membranous nephropathy. CONCLUSIONS: This case highlights a novel and treatable secondary cause of membranous nephropathy. Because secondary causes are more common in children than in adults, a high index of suspicion for other underlying pathology including malignancy should be considered. It also suggests that urinalysis may be a helpful screening tool in cases of angiomatoid fibrous histiocytoma.

Inpatient health care utilization in the United States among children, adolescents, and young adults with nephrotic syndrome.

BACKGROUND: Data describing inpatient health care utilization in children with nephrotic syndrome and related severe complications are limited. Our goals were to describe the charges, length of stay (LOS), and number of hospitalizations among children, adolescents, and young adults with nephrotic syndrome. STUDY DESIGN: A cross-sectional analysis of the Kids' Inpatient Database (KID) database from the Healthcare Cost and Utilization Project (HCUP). The HCUP-KID is an all-payer database of hospital discharges for children, adolescents, and young adults in the United States compiled every 3 years by the Agency for Healthcare Research and Quality. SETTING & PARTICIPANTS: HCUP-KID data were obtained for the 2006 and 2009 cohort years. We identified patients by searching discharges for nephrotic syndrome International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. PREDICTOR: Patient demographics, disease complications in children, adolescents, and young adults hospitalized with nephrotic syndrome. OUTCOME: Number of hospitalizations, mean charges, and LOS for children, adolescents, and young adults hospitalized with nephrotic syndrome. RESULTS: There were 6,308 hospitalization discharges in children, adolescents, and young adults with a primary or secondary diagnosis of nephrotic syndrome reported by 38 and 44 states in 2006 and 2009, respectively, representing an estimated 9,934 discharges nationally. Nephrotic syndrome resulted in an estimated 48,700 inpatient days and charges totaling $259 million. The mean charge per hospitalization was ∼$26,500 (SE, $1,100) and LOS was 5 days (SE, 0.1). 16% of discharges for nephrotic syndrome had a diagnosis code for at least one severe complication, including thromboembolism (3.6%), septicemia (3.8%), peritonitis (2.6%), pneumonia (5.4%), or diabetes (2.4%). Multivariable analysis showed age 15 years or older, race, higher socioeconomic status, acute renal failure, thromboembolic disease, hypertension, and infections predicted higher mean hospitalization charges. LIMITATIONS: The HCUP-KID database collects data on a hospitalization level. Consequently, health care utilization on an individual patient level or in the outpatient environment is not possible. CONCLUSIONS: We present a comprehensive description of inpatient health care utilization in children, adolescents, and young adults with nephrotic syndrome. The complications of nephrotic syndrome, including thromboembolism, infection, and hypertension, contribute significantly to these charges.

Treatment outcome of late steroid-resistant nephrotic syndrome: a study by the Midwest Pediatric Nephrology Consortium.

BACKGROUND: Idiopathic nephrotic syndrome (NS) in children is classified as steroid sensitive or steroid resistant. Steroid sensitivity typically portends a low risk of permanent renal failure. However, some initially steroid-sensitive patients later develop steroid resistance. These patients with late steroid resistance (LSR) are often treated with immunosuppressant medications, but the effect of these additional drugs on the long-term prognosis of LSR is still unknown. METHODS: A retrospective chart review was performed on patients diagnosed with idiopathic NS and subsequent LSR during the 8-year study period from 2002 up to and including 2009, with a minimum of 2 years of follow-up. Primary outcome measures were proteinuria and renal function. RESULTS: A total of 29 patients were classified as having LSRNS. The majority of patients received treatment with calcineurin inhibitors and/or mycophenolate mofetil. Seven patients received three or more non-steroid immunosuppressant medications. Sustained complete or partial remission was achieved in 69 % of patients. Three developed end-stage renal disease, and all others maintained normal renal function. There were 13 episodes of serious adverse events, none of which were fatal or irreversible. CONCLUSION: Most patients with LSRNS responded to immunosuppressive therapy by reduction or resolution of proteinuria and preservation of renal function. The results suggest that immunosuppressive treatment is a viable option in NS patients who develop LSR.

A 7-Year-Old Boy with Fever and Dark Urine.

A 7-Year-Old Boy with Fever and Dark UrineA 7-year-old boy with surgically repaired tetralogy of Fallot presented for evaluation of fever and dark urine. How do you approach the evaluation, and what is the diagnosis?

Skimmed breast milk for treatment of hypertriglyceridemia in an infant with congenital nephrotic syndrome.

Congenital nephrotic syndrome (CNS) is a complex condition that requires multidisciplinary care. Hyperlipidemia is a characteristic feature with elevation of serum cholesterol and triglycerides. Little evidence is available to guide treatment of dyslipidemia in infants with CNS. We describe successful treatment of severe hypertriglyceridemia through dietary changes in a boy with CNS. A 9-day-old boy presented to the emergency department with lower extremity edema caused by deep venous thrombosis. Laboratory evaluation identified hypoalbuminemia, nephrotic-range proteinuria, and a pathogenic variant of the NPHS1 gene. The initial triglyceride concentration of 369 mg/dl increased to 3096 mg/dl by 5 weeks of age, when his diet consisted of breast milk. Refrigerated breast milk was skimmed by removing the top layer after allowing it to separate for 24 h. This process was repeated prior to use. Skimmed breast milk was supplemented with medium-chain triglyceride oil and an infant protein powder. After 2 days, the triglyceride concentration declined to 481 mg/dl and, by day 10, to 148 mg/dl. When breast milk supply decreased, a 1:1 ratio of skimmed maternal breast milk to an elemental, very low-fat formula was utilized. The triglyceride concentration remained below 400 mg/dl for the first year of life, except when skimmed breast milk was not available during hospitalization. Severe hypertriglyceridemia caused by CNS can present in the neonatal period and be difficult to manage. In our patient, skimmed maternal breast milk was successful in reducing the triglyceride concentration and should be considered a therapeutic option for children with hyperlipidemia caused by CNS.

Validating a Computable Phenotype for Nephrotic Syndrome in Children and Adults Using PCORnet Data.

Background: Primary nephrotic syndromes are rare diseases which can impede adequate sample size for observational patient-oriented research and clinical trial enrollment. A computable phenotype may be powerful in identifying patients with these diseases for research across multiple institutions. Methods: A comprehensive algorithm of inclusion and exclusion ICD-9 and ICD-10 codes to identify patients with primary nephrotic syndrome was developed. The algorithm was executed against the PCORnet CDM at three institutions from January 1, 2009 to January 1, 2018, where a random selection of 50 cases and 50 noncases (individuals not meeting case criteria seen within the same calendar year and within 5 years of age of a case) were reviewed by a nephrologist, for a total of 150 cases and 150 noncases reviewed. The classification accuracy (sensitivity, specificity, positive and negative predictive value, F1 score) of the computable phenotype was determined. Results: The algorithm identified a total of 2708 patients with nephrotic syndrome from 4,305,092 distinct patients in the CDM at all sites from 2009 to 2018. For all sites, the sensitivity, specificity, and area under the curve of the algorithm were 99% (95% CI, 97% to 99%), 79% (95% CI, 74% to 85%), and 0.9 (0.84 to 0.97), respectively. The most common causes of false positive classification were secondary FSGS (nine out of 39) and lupus nephritis (nine out of 39). Conclusion: This computable phenotype had good classification in identifying both children and adults with primary nephrotic syndrome utilizing only ICD-9 and ICD-10 codes, which are available across institutions in the United States. This may facilitate future screening and enrollment for research studies and enable comparative effectiveness research. Further refinements to the algorithm including use of laboratory data or addition of natural language processing may help better distinguish primary and secondary causes of nephrotic syndrome.

Pediatric Immunization Practices in Nephrotic Syndrome: An Assessment of Provider and Parental Knowledge.

Background: Children with nephrotic syndrome (NS) are at high risk for vaccine-preventable infections due to the immunological effects from the disease and concurrent treatment with immunosuppressive medications. Immunizations in these patients may be deferred due to their immunosuppressive treatment which may increase the risk for vaccine-preventable infections. Immunization practices in children with NS continue to vary among pediatric nephrologists. This raises the question of whether children with NS are receiving the recommended vaccinations at appropriate times. Therefore, it is critical to understand the practices and patient education provided by physicians to patients on the topic of vaccinations. Methods: After informed consent, parents/guardians of 153 pediatric patients (<18 years old) diagnosed with NS from 2005 to 2018 and 50 pediatric nephrologists from 11 participating centers completed anonymous surveys to evaluate immunization practices among pediatric nephrologists, assess the vaccine education provided to families of children with NS, assess the parental knowledge of immunization recommendations, and assess predictors of polysaccharide pneumococcal vaccine adherence. The Advisory Committee on Immunization Practices (ACIP) Immunization 2019 Guideline for those with altered immunocompetence was used to determine accuracy of vaccine knowledge and practices. Results: Forty-four percent of providers self-reported adherence to the ACIP guidelines for inactive vaccines and 22% to the guidelines for live vaccines. Thirty-two percent of parents/guardians reported knowledge that aligned with the ACIP guidelines for inactive vaccines and 1% for live vaccines. Subjects residing in the Midwest and provider recommendations for vaccines were positive predictors of vaccine adherence (p < 0.001 and p 0.02, respectively). Conclusions: Vaccine recommendation by medical providers is paramount in vaccine adherence among pediatric patients with NS. This study identifies potential educational opportunities for medical subspecialty providers and family caregivers about immunization recommendations for immunosuppressed patients.

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.