Growth in children with nephrotic syndrome: a post hoc analysis of the NEPTUNE study.

BACKGROUND: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. METHODS: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. RESULTS: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (ß - 7.5 × 10-6, CI - 1.2 × 10-5, - 3 × 10-6, p = 0.001) and incident cases of NS (vs. prevalent) (ß - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (ß 0.16, CI 0.04, 0.29, p = 0.01) over time. CONCLUSION: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score.

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.

Developing an Edema Clinician-Reported Outcome Measure for Nephrotic Syndrome.

Introduction: Edema is a common manifestation of proteinuric kidney diseases, but there is no consensus approach for reliably evaluating edema. The objective of this study was to develop an edema clinician-reported outcome measure for use in patients with nephrotic syndrome. Methods: A literature review was conducted to assess existing clinician-rated measures of edema. Clinical experts were recruited from internal medicine, nephrology, and pediatric nephrology practices to participate in concept elicitation using semi-structured interviews and cognitive debriefing. Qualitative analysis methods were used to collate expert input and inform measurement development. In addition, training and assessment modules were developed using an iterative process that also utilized expert input and cognitive debriefing to ensure interrater reliability. Results: While several clinician-rated measures of edema have been proposed, our literature review did not identify any studies to support the reliability or validity of these measures. Fourteen clinician experts participated in the concept elicitation interviews, and twelve participated in cognitive debriefing. A clinician-reported outcome measure for edema was developed. The measure assesses edema severity in multiple individual body parts. An online training module and assessment tool were generated and refined using additional clinician input and investigative team expertise. Conclusion: The Edema ClinRO (V1) measure is developed specifically to measure edema in nephrotic syndrome. The tool assesses edema across multiple body parts, and it includes a training module to ensure standardized administration across raters. Future examination of this measure is ongoing to establish its reliability and validity.

Clustering-based spatial analysis (CluSA) framework through graph neural network for chronic kidney disease prediction using histopathology images.

Machine learning applied to digital pathology has been increasingly used to assess kidney function and diagnose the underlying cause of chronic kidney disease (CKD). We developed a novel computational framework, clustering-based spatial analysis (CluSA), that leverages unsupervised learning to learn spatial relationships between local visual patterns in kidney tissue. This framework minimizes the need for time-consuming and impractical expert annotations. 107,471 histopathology images obtained from 172 biopsy cores were used in the clustering and in the deep learning model. To incorporate spatial information over the clustered image patterns on the biopsy sample, we spatially encoded clustered patterns with colors and performed spatial analysis through graph neural network. A random forest classifier with various groups of features were used to predict CKD. For predicting eGFR at the biopsy, we achieved a sensitivity of 0.97, specificity of 0.90, and accuracy of 0.95. AUC was 0.96. For predicting eGFR changes in one-year, we achieved a sensitivity of 0.83, specificity of 0.85, and accuracy of 0.84. AUC was 0.85. This study presents the first spatial analysis based on unsupervised machine learning algorithms. Without expert annotation, CluSA framework can not only accurately classify and predict the degree of kidney function at the biopsy and in one year, but also identify novel predictors of kidney function and renal prognosis.

Patient-Reported Outcomes Over 24 Months in Pediatric CKD: Findings From the MyKidneyHealth Cohort Study.

RATIONALE & OBJECTIVE: The lived experience of children with chronic kidney disease (CKD) is poorly characterized. We examined the associations between patient-reported outcome (PRO) scores measuring their fatigue, sleep health, psychological distress, family relationships, and global health with clinical outcomes over time in children, adolescents, and younger adults with CKD and investigated how the PRO scores of this group compare with those of other children, adolescents, and younger adults. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 212 children, adolescentss, and adults aged 8 to 21 years with CKD and their parents recruited from 16 nephrology programs across North America. PREDICTORS: CKD stage, disease etiology, and sociodemographic and clinical variables. OUTCOME: PRO scores over 2 years. ANALYTICAL APPROACH: We compared PRO scores in the CKD sample with a nationally representative general pediatric population (ages 8 to 17 years). Change of PROs over time and association of sociodemographic and clinical variables with PROs were assessed using multivariable regression models. RESULTS: For all time points, 84% of the parents and 77% of the children, adolescents, and younger adults completed PRO surveys . The baseline PRO scores for the participants with CKD revealed a higher burden of fatigue, sleep-related impairment, psychological distress, impaired global health, and poorer family relationships compared with the general pediatric population, with median score differences≥1 SD for fatigue and global health. The baseline PRO scores did not differ by CKD stage or glomerular versus nonglomerular etiology. Over 2 years, PROs were stable with a<1-point annual change on average on each measure and intraclass correlation coefficients ranging from 0.53 to 0.79, indicating high stability. Hospitalization and parent-reported sleep problems were associated with worse fatigue, psychological health, and global health scores (all P<0.04). LIMITATIONS: We were unable to assess responsiveness to change with dialysis or transplant. CONCLUSIONS: Children with CKD experience a high yet stable burden of impairment across numerous PRO measures, especially fatigue and global health, independent of disease severity. These findings underscore the importance of assessing PROs, including fatigue and sleep measures, in this vulnerable population. PLAIN-LANGUAGE SUMMARY: Children with chronic kidney disease (CKD) have many treatment demands and experience many systemic effects. How CKD impacts the daily life of a child is poorly understood. We surveyed 212 children, adolescents, and younger adults with CKD and their parents over 24 months to assess the participants' well-being over time. Among children, adolescents, and younger adults with CKD we found a very high and persistent burden of psychological distress that did not differ by degree of CKD or type of kidney disease. The participants with CKD endorsed greater impairment in fatigue and global health compared with healthy children, adolescents, and younger adults, and parent-reported sleep problems were associated with poorer patient-reported outcome (PRO) scores across all domains. These findings emphasize the importance of including PRO measures, including fatigue and sleep measures, into routine clinical care to optimize the lived experience of children with CKD.

Genetic Spectrum of Nephrotic Syndrome: Impact of Podocytopathy in Adult Life.

A substantial number of patients with focal segmental glomerulosclerosis (FSGS) have a pathogenic genetic mutation in a podocyte protein as the cause of their disease. The mutations can affect a wide range of cell functions including the actin cytoskeleton, cell adhesion and motility, mitochondrial function, and nuclear pore proteins. The likelihood of a genetic cause declines with age, from approximately 30% in children and adolescents to 10% in adulthood, and the specific proteins involved and the pattern of inheritance differ in the 2 age groups. The presence of a genetic cause for FSGS can have important clinical ramifications including the need for a diagnostic kidney biopsy, medical management, and the risk of recurrent disease after kidney transplantation. This review summarizes the spectrum of genetic causes of nephrotic syndrome, primarily FSGS, in adults with a focus on diagnosis, presentation, and management.

Comparing Kidney Health Outcomes in Children, Adolescents, and Adults With Focal Segmental Glomerulosclerosis.

Importance: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials. Objective: To examine whether there are differences in the kidney health outcomes among children, adolescents, and adults with FSGS. Design, Setting, and Participants: This cohort study used pooled and parallel analyses, completed July 5, 2022, from 3 complimentary data sources: (1) Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE); (2) FSGS clinical trial (FSGS-CT); and (3) Kidney Research Network (KRN). NEPTUNE is a multicenter US/Canada cohort study; FSGS-CT is a multicenter US/Canada clinical trial; and KRN is a multicenter US electronic health record-based registry from academic and community nephrology practices. NEPTUNE included 166 patients with incident FSGS enrolled at first kidney biopsy; FSGS-CT included 132 patients with steroid-resistant FSGS randomized to cyclosporine vs dexamethasone with mycophenolate; and KRN included 184 patients with prevalent FSGS. Data were collected from November 2004 to October 2019 and analyzed from October 2020 to July 2022. Exposures: Age: children (age <13 years) vs adolescents (13-17 years) vs adults (≥18 years). Covariates of interest included sex, disease duration, APOL1 genotype, urine protein-to-creatinine ratio, estimated glomerular filtration rate (eGFR), edema, serum albumin, and immunosuppressive therapy. Main Outcomes and Measures: ESKD, composite outcome of ESKD or 40% decline in eGFR, and complete and/or partial remission of proteinuria. Results: The study included 127 (26%) children, 102 (21%) adolescents, and 253 (52%) adults, including 215 (45%) female participants and 138 (29%) who identified as Black, 98 (20%) who identified as Hispanic, and 275 (57%) who identified as White. Overall, the median time to ESKD was 11.9 years (IQR, 5.2-19.1 years). There was no difference in ESKD risk among children vs adults (hazard ratio [HR], 0.67; 95% CI, 0.43-1.03) or adolescents vs adults (HR, 0.85; 95% CI, 0.52-1.36). The median time to the composite end point was 5.7 years (IQR 1.6-15.2 years), with hazard ratio estimates for children vs adults of 1.12 (95% CI, 0.83-1.52) and adolescents vs adults of 1.06 (95% CI, 0.75-1.50). Conclusions and Relevance: In this study, the association of FSGS with kidney survival and functional outcomes was comparable at all ages.

The Health Economic Impact of Nephrotic Syndrome in the United States.

Background: Nephrotic syndrome (NS) is a rare kidney syndrome with high morbidity. Although a common contributor to the burden of chronic kidney disease, the direct and indirect costs of NS to patients and family caregivers are unrecognized. The objective was to characterize the direct and indirect costs of NS to patients. Methods: Adults with NS and family caregivers of children with NS were eligible to participate if they had a diagnosis of primary NS, had disease for at least 1 year, and had no other severe health conditions. Data-collection surveys were generated with input from the Kidney Research Network Patient Advisory Board, and surveys were mailed to the eligible participants. Participants were provided $50 for the return of completed surveys. Costs were defined as either direct out-of-pocket costs or indirect costs (e.g., time). Descriptive statistics, including percentage and median (interquartile range [IQR]) are reported. Results: Respondents included 28 adult patients and 17 caregivers of patients who were minors. Reported health insurance coverage included 35 (78%) with private insurance, 12 (27%) with public insurance, six (13%) with Children's Special Health Care Services, and one (2%) uninsured. Median annual direct costs were $3464 ($844-$5865) for adult patients and $1687 (IQR $1035-$4763) for caregivers. Of these costs, diet-associated costs contributed $1140 (IQR $600-$2400). The most substantial indirect cost was from the time spent planning/prepping meals (adults: 183 h/yr [IQR 114-331]; caregivers: 173 h/yr [IQR 84-205]). Conclusions: Adults and caregivers of children with NS face substantial disease-related direct and indirect costs beyond those covered by insurance. Following replication, the study will help health care providers, systems, and payers gain a better understanding of the financial and time burden incurred by those living with NS, consider barriers when treating patients, and develop supportive strategies.

Unsupervised machine learning for identifying important visual features through bag-of-words using histopathology data from chronic kidney disease.

Pathologists use visual classification to assess patient kidney biopsy samples when diagnosing the underlying cause of kidney disease. However, the assessment is qualitative, or semi-quantitative at best, and reproducibility is challenging. To discover previously unknown features which predict patient outcomes and overcome substantial interobserver variability, we developed an unsupervised bag-of-words model. Our study applied to the C-PROBE cohort of patients with chronic kidney disease (CKD). 107,471 histopathology images were obtained from 161 biopsy cores and identified important morphological features in biopsy tissue that are highly predictive of the presence of CKD both at the time of biopsy and in one year. To evaluate the performance of our model, we estimated the AUC and its 95% confidence interval. We show that this method is reliable and reproducible and can achieve 0.93 AUC at predicting glomerular filtration rate at the time of biopsy as well as predicting a loss of function at one year. Additionally, with this method, we ranked the identified morphological features according to their importance as diagnostic markers for chronic kidney disease. In this study, we have demonstrated the feasibility of using an unsupervised machine learning method without human input in order to predict the level of kidney function in CKD. The results from our study indicate that the visual dictionary, or visual image pattern, obtained from unsupervised machine learning can predict outcomes using machine-derived values that correspond to both known and unknown clinically relevant features.

Health-Related Quality of Life in Focal Segmental Glomerular Sclerosis and Minimal Change Disease: A Qualitative Study of Children and Adults to Inform Patient-Reported Outcomes.

RATIONALE & OBJECTIVE: Assessment of how patients feel and function is needed for clinical care and research for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). The objective of this study was to develop a patient-reported outcome assessment appropriate for use in children and adults with FSGS and MCD. STUDY DESIGN: Qualitative study using semi-structured interviews. SETTING & PARTICIPANTS: 48 semi-structured interviews with children aged 8 to 17 years (n = 11) and adults (n = 10) with FSGS and children aged 8 to 17 (n = 11) and adults (n = 16) with MCD recruited from 3 academic medical centers. ANALYTICAL APPROACH: Latent content analysis. RESULTS: FSGS and MCD have a pervasive and comparable impact on physical, social, and mental health-related quality of life regardless of age or diagnosis. Physical symptoms of swelling, fatigue, and pain were articulated by most participants. Disease management was also a frequent topic of discussion; participants described their experiences with medication and associated side effects, as well as lifestyle changes made to manage their disease (ie, dietary changes and frequent medical appointments). These discussions often identified a profound impact on physical abilities and life participation. In many instances, participants described the negative impact these symptoms had on their mood and sense of self, with most participants reporting feelings of anxiety. LIMITATIONS: Participants were primarily non-Hispanic White and English speaking, which may limit generalizability. CONCLUSIONS: Our results suggest that there are commonalities to the FSGS-MCD patient experience of health-related quality of life that will enable the generation of a disease-specific FSGS-MCD patient-reported outcomes instrument for use in children and adults. The development of this tool is intended to facilitate better care and support clinical research for these individuals.

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.

The Development and Use of an EHR-Linked Database for Glomerular Disease Research and Quality Initiatives.

Background and Objective: The use of electronic health record (EHR) data can facilitate efficient research and quality initiatives. The imprecision of ICD-10 codes for kidney diagnoses has been an obstacle to discrete data-defined diagnoses in the EHR. This manuscript describes the Kidney Research Network (KRN) registry and database that provide an example of a prospective, real-world data glomerular disease registry for research and quality initiatives. Methods: KRN is a multicenter collaboration of patients, physicians, and scientists across diverse health-care settings with a focus on improving treatment options and outcomes for patients with glomerular disease. The registry and data warehouse amasses retrospective and prospective data including EHR, active research study, completed clinical trials, patient reported outcomes, and other relevant data. Following consent, participating sites enter the patient into KRN and provide a physician-confirmed primary kidney diagnosis. Kidney biopsy reports are redacted and uploaded. Site programmers extract local EHR data including demographics, insurance type, zip code, diagnoses, encounters, laboratories, procedures, medications, dialysis/transplant status, vitals, and vital status monthly. Participating sites transform data to conform to a common data model prior to submitting to the Data Analysis and Coordinating Center (DACC). The DACC stores and reviews each site's EHR data for quality before loading into the KRN database. Results: As of January 2021, 1,192 patients have enrolled in the registry. The database has been utilized for research, clinical trial design, clinical trial end point validation, and supported quality initiatives. The data also support a dashboard allowing enrolling sites to assist with clinical trial enrollment and population health initiatives. Conclusion: A multicenter registry using EHR data, following physician- and biopsy-confirmed glomerular disease diagnosis, can be established and used effectively for research and quality initiatives. This design provides an example which may be readily replicated for other rare or common disease endeavors.

Association between Psychiatric Disorders and Glomerular Disease.

Introduction: Patients with chronic health conditions, particularly chronic kidney disease, are at heightened risk for psychiatric disorders; yet, there are limited data on those with primary glomerular disease. Methods: This study included patients with glomerular disease enrolled in the kidney research network multisite patient registry. Registry data include encounter, diagnoses, medication, laboratory, and vital signs data extracted from participants' electronic health records. ICD-9/10 diagnosis codes were used to identify a subset of psychiatric disorders focused on anxiety, mood, and behavioral disorders. Time-varying Cox proportional hazard models were used to analyze time from the onset of kidney disease to diagnosis of psychiatric disorder. Adjusted models retained significant covariates from the full list of potential confounders, including age, sex, race, ethnicity, time-varying treatment, the estimated glomerular filtration rate, and proteinuria (urine protein-to-creatinine ratio [UPCR]). Analogous models examined diagnosis of psychiatric disorder as a predictor of time to end-stage kidney disease (ESKD). Results: Data were available for 950 participants, with a median of 58 months of follow-up. 110 (12%) participants were diagnosed with psychiatric disorder during the follow-up. The estimated rate of psychiatric diagnosis after kidney disease was 14.7 cases per 1,000 person-years and was highest among those of adolescent age at the time of kidney disease diagnosis. Adjusted analyses found adolescent age (vs. adult, hazard ratio [HR] = 3.11, 95% confidence interval [CI] 1.87-5.17) and Asian race (vs. white, HR = 0.34, 95% CI 0.16-0.71) were associated with psychiatric diagnosis. A higher UPCR per 1 log unit (HR 1.13, 95% CI 1.01-1.27) and a higher total number of oral medications were associated with psychiatric disorder (p < 0.001). Psychiatric diagnosis was also associated with progression to ESKD (HR = 2.45, 95% CI 1.53-3.92) in adjusted models. Discussion/Conclusion: Psychiatric disorders were documented in approximately one-eighth of patients with glomerular disease and correlated with clinical disease characteristics such as age, race, proteinuria, and oral medication burden. These findings suggest mental health screening is warranted in patients of all ages with glomerular disease.

Time to Initiation of Antihypertensive Therapy After Onset of Elevated Blood Pressure in Patients With Primary Proteinuric Kidney Disease.

RATIONALE & OBJECTIVE: The objective of the study was to estimate the prevalence of hypertension in patients with proteinuric kidney disease and evaluate blood pressure (BP) control. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Data from adults and children with proteinuric kidney disease enrolled in the multicenter Kidney Research Network Registry were used for this study. EXPOSURE: Proteinuric kidney disease. OUTCOMES: Hypertension and BP control. ANALYTICAL APPROACH: Patients with white-coat hypertension were excluded. Patients were censored at end-stage kidney disease onset. Patients were defined as hypertensive either by hypertension diagnosis code, having 2 or more encounters with elevated BPs, or treatment with antihypertensive therapy excluding renin-angiotensin-aldosterone system blockade. Elevated BP was defined as greater than 95th percentile for children and >140/90 mm Hg in adults. Sustained BP control was defined as 2 or more consecutive encounters with BPs lower than 95th percentile for children and <140/90 mm Hg for adults. Kaplan-Meier and Cox proportional hazards analyses were used to evaluate the time to initiation of antihypertensive therapy. RESULTS: 842 patients, 69% adults and 31% children, with a total observation period of 6,722 patient-years were included in the analysis. 644 (76%) had hypertension during observation. There was no difference in the prevalence of hypertension between children and adults (74% vs 78%; P = 0.3). Hypertension was most common among those of African American race compared with other races (90% vs 72%-75%; P = 0.003). 504 (78%) patients with hypertension achieved BP control but only 51% achieved control within 1 year. 140 (22%) patients with hypertension never achieved BP control during a median of 41 (IQR, 24-73) months of observation. LIMITATIONS: Differing BP control goals that may lead to overestimation of the controlled patient population. CONCLUSIONS: Hypertension affects most patients with proteinuric kidney disease regardless of age. Time to BP control exceeded 1 year in 50% of patients with hypertension and 22% did not demonstrate control. This study highlights the need to address hypertension early and completely in disease management of patients with proteinuric kidney disease.

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.

Using PROMIS® to create clinically meaningful profiles of nephrotic syndrome patients.

OBJECTIVE: Nephrotic syndrome (NS) is a kidney disease known to adversely impact health-related quality of life (HRQOL). Patient-reported outcome (PRO) measures are commonly used to characterize HRQOL and the patient disease experience. This study aims to improve the interpretability and clinical utility of the Patient-Reported Outcomes Measurement Information System® (PROMIS®) by identifying distinct meaningful HRQOL profiles in children and adults with NS. METHOD: Patients were from 2 prospective NS cohort studies (PROMIS-II®: 121 children; NEPTUNE: 40 children and 219 adults) with data from 6 PROMIS® domains. Latent Profile Analysis was used to identify subgroups of patients based on PROMIS® score patterns. A 3-step analysis of latent profile predictors was used to determine how clinical parameters predicted HRQOL profile membership. RESULTS: We identified 3 HRQOL profiles (Good, Average, and Poor) with strong indicators of membership classification (entropy >0.86). Complete proteinuria remission, reduction in symptoms, and shorter disease duration, were significant predictors of better HRQOL profile membership. CONCLUSIONS: Patients with NS can be classified by HRQOL into clinically meaningful categories. Integrating this approach into clinic may help in the identification of individuals with poor HRQOL will help clinicians better manage their symptoms and researchers study the causes and possible interventions for these patients. PROMIS® HRQOL profiles were reproducible in replication cohorts. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Steroid-Associated Side Effects in Patients With Primary Proteinuric Kidney Disease.

INTRODUCTION: The goal of this study was to assess the occurrence of steroid-associated adverse events (SAAE) in patients with primary proteinuric kidney disease. METHODS: The Kidney Research Network Registry consists of children and adults with primary proteinuric kidney disease. SAAEs of interest were hypertension, hyperglycemia and diabetes, overweight and obesity, short stature, ophthalmologic complications, bone disorders, infections, and psychosis. Events were identified using International Classification of Diseases, Ninth Revision/Tenth Revision codes, blood pressures, growth parameters, laboratory values, and medications. Poisson generalized estimating equations tested the association between steroid onset and dose on SAAE risk. RESULTS: A total of 884 participants were included in the analysis; 534 (60%) were treated with steroids. Of these, 62% had at least one SAAE. The frequency of any SAAE after initiation of steroids was 293 per 1000 person-years. The most common SAAEs were hypertension (173.7 per 1000 person-years), diabetes (78.7 per 1000 person-years), obesity (66.8 per 1000 person-years), and infections (46.1 per 1000 person-years). After adjustment for demographics, duration of kidney disease, estimated glomerular filtration rate (eGFR), proteinuria, and other therapies, steroid exposure was associated with a 40% increase in risk of any SAAE (Relative risk [RR]: 1.4; 95% confidence interval [CI]: 1.3-1.6). A 1-mg/kg per day increase in steroid dose was associated with a 2.5-fold increase in risk of any SAAE. CONCLUSION: Most patients with primary proteinuric kidney disease treated with steroids experienced at least one SAAE. Steroid therapy increased risk of hypertension, diabetes, weight gain, short stature, fractures, and infections after adjusting for disease-related factors. This study highlights the importance of surveillance and management of SAAE and provides rationale for the development of steroid minimization protocols.

Consent for Genetic Biobanking in a Diverse Multisite CKD Cohort.

INTRODUCTION: The goal of this study was to examine patterns in the likelihood of consent to genetic research among participants in a prospective kidney disease cohort and biobank, and to determine demographic, clinical, and socioeconomic factors linked to consent for ongoing and future genetic research. METHODS: The Clinical Phenotyping Resource and Biobank Core (C-PROBE) enrolled 1628 adult and pediatric patients with chronic kidney disease from 2009 to 2017 across 7 sites in the United States. Participants were asked at annual study visits for consent to provide DNA samples for future genetic studies. We compared characteristics of participants by initial consent outcome and consent status at their most recent study visit. RESULTS: Of the C-PROBE participants, 96% consented to genetic studies at their initial study visit. Although African Americans were slightly less likely to consent at baseline (93% vs. 97%, odds ratio = 0.3, P < 0.02), there were no significant racial or ethnic differences with longitudinal participation. Also, pediatric and adult genetic consent rates were equivalent. The major persistent differences in the likelihood of consent were based on enrollment site, which ranged from 85% to 100% (P < 0.0001). CONCLUSION: Overall, genetic consent rates for kidney research within the C-PROBE cohort were high. However, differences in consent rates over time and by recruitment site highlight the complexity of genetic consent for biobanking, and potential limitations for generalizability of observations.