Clinical practice guideline for the prevention and management of peritoneal dialysis associated infections in children: 2024 update.

Infection-related complications remain the most significant cause for morbidity and technique failure in infants, children and adolescents who receive maintenance peritoneal dialysis (PD). The 2024 update of the Clinical Practice Guideline for the Prevention and Management of Peritoneal Dialysis Associated Infection in Children builds upon previous such guidelines published in 2000 and 2012 and provides comprehensive treatment guidance as recommended by an international group of pediatric PD experts based upon a review of published literature and pediatric PD registry data. The workgroup prioritized updating key clinical issues contained in the 2012 guidelines, in addition to addressing additional questions developed using the PICO format. A variety of new guideline statements, highlighted by those pertaining to antibiotic therapy of peritonitis as a result of the evolution of antibiotic susceptibilities, antibiotic stewardship and clinical registry data, as well as new clinical benchmarks, are included. Recommendations for future research designed to fill important knowledge gaps are also provided.

The Preserving Kidney Function in Children With CKD (PRESERVE) Study: Rationale, Design, and Methods.

Rationale & Objective: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management. Study Design: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]). Setting & Participants: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were ≥1 nephrologist visit and ≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to <90 mL/min/1.73 m2 separated by ≥90 days without an intervening value ≥90 mL/min/1.73 m2 and no prior dialysis or kidney transplant. Exposures: BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class. Outcomes: The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of <15 mL/min/1.73 m2, long-term dialysis or kidney transplant. Secondary outcomes include change in eGFR, adverse events, and PROs. Analytical Approach: Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics. Limitations: Causal inference limited by observational analyses. Conclusions: PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients. Plain-Language Summary: Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in PCORnet, the National Patient-Centered Clinical Research Network, and includes electronic health record data for >19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management.

Standardizing Blood Pressure Measurements in Pediatric Hemodialysis: a Collaborative Journey.

PURPOSE OF REVIEW: This manuscript details the development and execution of a quality improvement (QI) initiative aimed at standardizing blood pressure (BP) measurement practices in pediatric hemodialysis (HD) units across a national dialysis collaborative. RECENT FINDINGS: Although there are recommendations for the detection and treatment of hypertension in the pediatric population, currently there is no data or recommendations specific to the methodology of measuring blood pressure in a pediatric hemodialysis setting. In 2016, the Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease (SCOPE) Collaborative assembled a dedicated working group to thoroughly examine BP measurement practices across participating pediatric HD centers and, drawing from current research, to establish a standardized best practice for BP measurement in pediatric HD patients both in-center and at home. Employing QI methodology, the working group devised a standardized "BP Bundle" and implemented it throughout the SCOPE Collaborative. This work led to successful practice improvement by establishing a consistent approach to BP measurement in pediatric HD patients cared for in SCOPE centers. With a standard best practice now in place and over 85% compliance with the BP Bundle across the SCOPE Collaborative, researchers and healthcare professionals can more accurately study and ultimately enhance the cardiovascular health of pediatric HD patients.

Training practices and peritonitis rates in children on maintenance peritoneal dialysis: results from the Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease (SCOPE) collaborative.

BACKGROUND: Comprehensive training of children on peritoneal dialysis (PD) and their caregivers is crucial to minimize peritonitis risk. Few studies have evaluated the impact of training on infection, so many published recommendations rely on expert opinion. This study uses data from the SCOPE collaborative to examine the impact of compliance with 4 components of PD training on the risk for peritonitis. METHODS: A retrospective cohort study of children enrolled in the SCOPE collaborative between 2011 and 2021 who received training prior to initiating PD. Compliance with 4 training components were assessed: performance of a home visit, 1:1 training, delaying training ≥ 10 days after PD catheter insertion and average individual training session length ≤ 3 h. Univariate and multivariable generalized linear mixed modeling were used to assess relationships between peritonitis ≤ 90 days after PD training and median days to peritonitis and compliance with each component as well as all-or-none compliance. RESULTS: Among 1450 trainings, 51.7% had median session length ≤ 3 h, 67.1% delayed training ≥ 10 days after catheter insertion, 74.3% had a home visit and 94.6% had 1:1 training. Only 333 trainings (23%) were compliant with all 4 training components. There was no statistically significant association between compliance with individual components, or all-or-none compliance and either the percentage of catheters with peritonitis ≤ 90 days after training end or median days to peritonitis. CONCLUSION: No associations between 4 PD training components and risk for peritonitis were found. SCOPE requires monthly review of PD catheter practices which may have decreased the impact of training non-compliance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Epidemiology and Risk Factors for Hemodialysis Access-Associated Infections in Children: A Prospective Cohort Study From the SCOPE Collaborative.

RATIONALE & OBJECTIVE: Infections cause significant morbidity and mortality for children receiving maintenance hemodialysis (HD). The Standardizing Care to Improve Outcomes in Pediatric End-Stage Kidney Disease (SCOPE) Collaborative is a quality-improvement initiative aimed at reducing dialysis-associated infections by implementing standardized care practices. This study describes patient-level risk factors for catheter-associated bloodstream infections (CA-BSIs) and examines the association between dialysis center-level compliance with standardized practices and risk of CA-BSI. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Children enrolled in SCOPE between June 2013 and July 2019. EXPOSURES: Data were collected on patient characteristics and center-level compliance with HD catheter care practices across the study period. Centers were categorized as consistent, dynamic (improved compliance over the study period), or inconsistent performers based on frequency of compliance audit submission and changes in compliance with HD care practices over time. OUTCOME: CA-BSIs. ANALYTICAL APPROACH: Generalized linear mixed models were used to evaluate (1) patient-level risk factors for CA-BSI and (2) associations between change in center-level compliance and CA-BSIs. RESULTS: The cohort included 1,277 children from 35 pediatric dialysis centers; 1,018 (79.7%) had a catheter and 259 (20.3%) had an arteriovenous fistula or graft. Among children with a catheter, mupirocin use at the catheter exit site was associated with an increased rate of CA-BSIs (rate ratio [RR], 4.45; P = 0.004); the use of no antibiotic agent at the catheter exit site was a risk factor of borderline statistical significance (RR, 1.79; P = 0.05). Overall median compliance with HD catheter care practices was 87.5% (IQR, 77.3%-94.0%). Dynamic performing centers showed a significant decrease in CA-BSI rates over time (from 2.71 to 0.71 per 100 patient-months; RR, 0.98; P < 0.001), whereas no significant change in CA-BSI rates was detected among consistent or inconsistent performers. LIMITATIONS: Lack of data on adherence to HD care practices on the individual patient level. CONCLUSIONS: Improvement in compliance with standardized HD care practices over time may lead to a reduction in dialysis-associated infections.

Continued reduction in peritonitis rates in pediatric dialysis centers: results of the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative.

BACKGROUND: In its first 3 years, the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative demonstrated a statistically significant increase in the likelihood of compliance with a standardized follow-up care bundle and a significant reduction in peritonitis. We sought to determine if compliance with care bundles and low peritonitis rates could be sustained in centers continuously participating for 84 months. METHODS: Centers that participated from collaborative launch through the 84-month study period and provided pre-launch peritonitis rates were included. Children on maintenance peritoneal dialysis were eligible for enrollment. Changes in bundle compliance were assessed using a logistic regression model or a generalized linear mixed model (GLMM). Changes in average annualized peritonitis rates over time were modeled using GLMMs. RESULTS: Nineteen centers contributed 1055 patients with 1268 catheters and 17,247 follow-up encounters. The likelihood of follow-up compliance increased significantly over the study period (OR 1.05 95% confidence interval (CI) 1.03, 1.07; p < 0.001). Centers achieved ≥ 80% follow-up bundle compliance by 28 months and maintained a mean compliance of 84% between 28 and 84 months post-launch. Average monthly peritonitis rates decreased from 0.53 (95% CI 0.37, 0.70) infections per patient-year pre-launch to 0.30 (95% CI 0.23, 0.43) at 84 months post-launch, p < 0.001. CONCLUSIONS: Centers participating in the SCOPE Collaborative for 84 months achieved and maintained a high level of compliance with a standardized follow-up care bundle and demonstrated a significant and continued reduction in average monthly peritonitis rates.

Opportunities to Improve Antibiotic Prescribing in Outpatient Hemodialysis Facilities: A Report From the American Society of Nephrology and Centers for Disease Control and Prevention Antibiotic Stewardship White Paper Writing Group.

Antibiotic use is necessary in the outpatient hemodialysis setting because patients receiving hemodialysis are at increased risk for infections and sepsis. However, inappropriate antibiotic use can lead to adverse drug events, including adverse drug reactions and infections with Clostridioides difficile and antibiotic-resistant bacteria. Optimizing antibiotic use can decrease adverse events and improve infection cure rates and patient outcomes. The American Society of Nephrology and the US Centers for Disease Control and Prevention created the Antibiotic Stewardship in Hemodialysis White Paper Writing Group, comprising experts in antibiotic stewardship, infectious diseases, nephrology, and public health, to highlight strategies that can improve antibiotic prescribing for patients receiving maintenance hemodialysis. Based on existing evidence and the unique patient and clinical setting characteristics, the following strategies for improving antibiotic use are reviewed: expanding infection and sepsis prevention activities, standardizing blood culture collection processes, treating methicillin-susceptible Staphylococcus aureus infections with ß-lactams, optimizing communication between nurses and prescribing providers, and improving data sharing across transitions of care. Collaboration among the Centers for Disease Control and Prevention; American Society of Nephrology; other professional societies such as infectious diseases, hospital medicine, and vascular surgery societies; and dialysis provider organizations can improve antibiotic use and the quality of care for patients receiving maintenance hemodialysis.

Optimizing Peritoneal Dialysis-Associated Peritonitis Prevention in the United States: From Standardized Peritoneal Dialysis-Associated Peritonitis Reporting and Beyond.

Peritoneal dialysis (PD)-associated peritonitis is the leading cause of permanent transition to hemodialysis among patients receiving PD. Peritonitis is associated with higher mortality risk and added treatment costs and limits more widespread PD utilization. Optimizing the prevention of peritonitis in the United States will first require standardization of peritonitis definitions, key data elements, and outcomes in an effort to facilitate nationwide reporting. Standardized reporting can also help describe the variability in peritonitis rates and outcomes across facilities in the United States in an effort to identify potential peritonitis prevention strategies and engage with stakeholders to develop strategies for their implementation. Here, we will highlight considerations and challenges in developing standardized definitions and implementation of national reporting of peritonitis rates by PD facilities. We will describe existing peritonitis prevention evidence gaps, highlight successful infection-reporting initiatives among patients receiving in-center hemodialysis or PD, and provide an overview of nationwide quality improvement initiatives, both in the United States and elsewhere, that have translated into a reduction in peritonitis incidence. We will discuss opportunities for collaboration and expansion of the Nephrologists Transforming Dialysis Safety (NTDS) initiative to develop knowledge translation pathways that will lead to dissemination of best practices in an effort to reduce peritonitis incidence.

Urinary Epidermal Growth Factor as a Marker of Disease Progression in Children With Nephrotic Syndrome.

INTRODUCTION: Childhood-onset nephrotic syndrome has a variable clinical course. Improved predictive markers of long-term outcomes in children with nephrotic syndrome are needed. This study tests the association between baseline urinary epidermal growth factor (uEGF) excretion and longitudinal kidney function in children with nephrotic syndrome. METHODS: The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. uEGF was measured at baseline for all participants and normalized by the urine creatinine (Cr) concentration. Renal epidermal growth factor (EGF) mRNA was measured in the tubular compartment microdissected from kidney biopsy cores from a subset of patients. Linear mixed models were used to test if baseline uEGF/Cr and EGF mRNA expression were associated with change in estimated glomerular filtration rate (eGFR) over time. RESULTS: Higher uEGF/Cr at baseline was associated with slower eGFR decline during follow-up (median follow-up = 30 months). Halving of uEGF/Cr was associated with a decrease in eGFR slope of 2.0 ml/min per 1.73 m2 per year (P < 0.001) adjusted for age, race, diagnosis, baseline eGFR and proteinuria, and APOL1 genotype. In the biopsied subgroup, uEGF/Cr was correlated with EGF mRNA expression (r = 0.74; P < 0.001), but uEGF/Cr was retained over mRNA expression as the stronger predictor of eGFR slope after multivariable adjustment (decrease in eGFR slope of 1.7 ml/min per 1.73 m2 per year per log2 decrease in uEGF/Cr; P < 0.001). CONCLUSION: uEGF/Cr may be a useful noninvasive biomarker that can assist in predicting the long-term course of kidney function in children with incident nephrotic syndrome.

Correction to: Eplet mismatch analysis and allograft outcome across racially diverse groups in a pediatric transplant cohort: a single-center analysis.

The original version of this article unfortunately contained a mistake. In the third paragraph of "Discussion," two references were missing.

Eplet mismatch analysis and allograft outcome across racially diverse groups in a pediatric transplant cohort: a single-center analysis.

HLA eplet mismatch load has been suggested as an improvement to HLA antigen mismatch determination for organ selection. Given that eplet mismatches are determined based on amino acid sequence difference among HLA alleles, and that the frequency of HLA alleles varies between racial groups, we investigated the correlation between eplet mismatch load and allograft outcomes in 110 pediatric kidney transplant recipients who received their first organ from a donor of the same race (SRT) versus a donor of a different race (DRT). Adjusted modified Poisson regression was used to assess the interaction between eplet mismatch load and race mismatch and its effect on outcome. Caucasians and living donor recipients had lower eplet mismatched loads against their donors compared with non-Caucasian and deceased donor recipients. Overall, for the entire population, the risk of de novo HLA-DSA development was significantly increased with higher eplet loads (p < 0.001). Compared with the SRT group, the DRT group had higher eplet loads when compared with their donor, for HLA class I but not HLA class II molecules; however, there was no significant difference in the incidence of de novo HLA-DSA between the 2 groups. The risk of rejection increased significantly for DRT compared with SRT, only when class I eplet load was ≥ 70 (p = 0.04). Together this data show that eplet mismatch load analysis is an effective tool for alloimmune risk assessment. If considered for donor selection, acceptable eplet mismatch loads determined from studies in homogenous populations may restrict transplantation across racially diverse donor and patient groups with no evidence of poor outcome. Therefore, an acceptable eplet mismatch load threshold must consider the heterogeneity of the transplant population.

A donor risk index for graft loss in pediatric living donor kidney transplantation.

Pediatric kidney transplant candidates often have multiple potential living donors (LDs); no evidence-based tool exists to compare potential LDs, or to decide between marginal LDs and deceased donor (DD) kidney transplantation (KT). We developed a pediatric living kidney donor profile index (P-LKDPI) on the same scale as the DD KDPI by using Cox regression to model the risk of all-cause graft loss as a function of living donor characteristics and DD KDPI. HLA-B mismatch (adjusted hazard ratio [aHR] per mismatch = 1.04 1.271.55 ), HLA-DR mismatch (aHR per mismatch = 1.02 1.231.49 ), ABO incompatibility (aHR = 1.20 3.268.81 ), donor systolic blood pressure (aHR per 10 mm Hg = 1.01 1.071.18 ), and donor estimated GFR (eGFR; aHR per 10 mL/min/1.73 m2 = 0.88 0.940.99 ) were associated with graft loss after LDKT. Median (interquartile range [IQR]) P-LKDPI was -25 (-56 to 12). 68% of donors had P-LKDPI <0 (less risk than any DD kidney) and 25% of donors had P-LKDPI >14 (more risk than median DD kidney among pediatric KT recipients during the study period). Strata of LDKT recipients of kidneys with higher P-LKDPI had a higher cumulative incidence of graft loss (39% at 10 years for P-LDKPI ≥20, 28% for 20> P-LKDPI ≥-20, 23% for -20 > P-LKDPI ≥-60, 19% for P-LKDPI <-60 [log rank P < .001]). The P-LKDPI can aid in organ selection for pediatric KT recipients by allowing comparison of potential LD and DD kidneys.

Factors associated with high-cost hospitalization for peritonitis in children receiving chronic peritoneal dialysis in the United States.

BACKGROUND: Although peritonitis causes significant morbidity and mortality in children receiving chronic peritoneal dialysis (CPD), little is known about costs associated with treatment. METHODS: We analyzed 246 peritonitis-related hospitalizations in the USA, linked by the Standardized Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) and Pediatric Health Information Systems (PHIS) databases. Multivariable logistic regression was used to assess the relationship between high-cost hospitalizations (at or above the 75th percentile) and patient characteristics. Multivariable modeling was used to assess differences in the service-line specific geometric mean between (1) high- and low-cost (below the 75th percentile) hospitalizations and (2) fungal versus other types of peritonitis. Wage-adjusted hospitalization charges were converted to estimated costs using reported cost-to-charge ratios to estimate the cost of hospitalization. RESULTS: High-cost hospitalizations were associated with the following: age 3-12 years, Hispanic ethnicity, intensive care unit (ICU) stay, length of stay (LOS), and fungal peritonitis. Whereas absolute standardized cost by service line was significantly different when comparing high- and low-cost hospitalizations, the percentage of total cost by service line was similar in the two groups. Cost per case for fungal peritonitis was higher (p < 0.001) in every service line except pharmacy when compared to other peritonitis cases. The median (IQR) cost of hospitalization for the treatment of peritonitis was $13,655 ($7871, $28434) USD. CONCLUSIONS: Hospitalization-related costs for peritonitis treatment are substantial and arise from a variety of service lines. Fungal peritonitis is associated with high-cost hospitalization.

Fungal peritonitis in the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative.

BACKGROUND: Fungal peritonitis is a serious complication among peritoneal dialysis (PD) patients. The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative is a North American multicenter quality improvement initiative with the primary aim to reduce catheter-related infections in children on chronic dialysis. OBJECTIVE: To describe the epidemiology of fungal peritonitis and outcomes of affected patients among pediatric subjects receiving chronic PD and enrolled in SCOPE. METHODS: Data pertaining to PD characteristics, peritonitis episodes and patient outcome were collected between October 2011 and September 2015 from 30 pediatric dialysis centers participating in the SCOPE collaborative. Peritonitis-related data were stratified by etiology, fungal versus bacterial/culture-negative peritonitis. Differences among groups were assessed by Chi-square analysis. RESULTS: Of 994 patients enrolled in the registry, there were 511 peritonitis episodes of which 41 (8.0%) were fungal. Thirty-six individual patients with 39 unique catheters accounted for the fungal peritonitis episodes. Twenty-three (59%) of the episodes occurred in patients aged < 2 years (p = 0.03). Fungal peritonitis was the initial episode of peritonitis in 48.8% of affected patients, and only 17.1% of these patients had had a previous peritonitis episode within 30 days of the fungal infection. Insertion of the PD catheter at < 2 years of age was associated with an adjusted odds ratio of 2.8 (95% confidence interval 1.24, 6.31) for development of fungal peritonitis compared to older children (p = 0.01). Fungal peritonitis was associated with an increased rate of hospitalization (80.5 vs. 63.4%; p = 0.03), increased length of hospitalization (median of 8 vs. 5 days; p < 0.001) and increased rates of catheter removal (84.6 vs 26.9%; p = 0.001) and technique failure (68.3 vs. 8%; p = 0.001) compared to other causes of peritonitis. CONCLUSION: Fungal infections were responsible for 8.0% of peritonitis episodes in the SCOPE collaborative, with the majority of fungal peritonitis episodes occurring in children aged < 2 years. Although no risk factors for infection other than young age were identified, fungal peritonitis was associated with an increased risk of hospitalization, longer hospital stay and an increased frequency of technique failure.

A contemporary approach to the prevention of peritoneal dialysis-related peritonitis in children: the role of improvement science.

Peritonitis is a leading cause of hospitalizations, morbidity, and modality change in pediatric chronic peritoneal dialysis (CPD) patients. Despite guidelines published by the International Society for Peritoneal Dialysis aimed at reducing the risk of peritonitis, registry data have revealed significant variability in peritonitis rates among centers caring for children on CPD, which suggests variability in practice. Improvement science methods have been used to reduce a variety of healthcare-associated infections and are also being applied successfully to decrease rates of peritonitis in children. A successful quality improvement program with the goal of decreasing peritonitis will not only include primary drivers directly linked to the outcome of peritonitis, but will also direct attention to secondary drivers that are important for the achievement of primary drivers, such as health literacy and patient and family engagement strategies. In this review, we describe a comprehensive improvement science model for the reduction of peritonitis in pediatric patients on CPD.

Implementation of standardized follow-up care significantly reduces peritonitis in children on chronic peritoneal dialysis.

The Standardizing Care to improve Outcomes in Pediatric End stage renal disease (SCOPE) Collaborative aims to reduce peritonitis rates in pediatric chronic peritoneal dialysis patients by increasing implementation of standardized care practices. To assess this, monthly care bundle compliance and annualized monthly peritonitis rates were evaluated from 24 SCOPE centers that were participating at collaborative launch and that provided peritonitis rates for the 13 months prior to launch. Changes in bundle compliance were assessed using either a logistic regression model or a generalized linear mixed model. Changes in average annualized peritonitis rates over time were illustrated using the latter model. In the first 36 months of the collaborative, 644 patients with 7977 follow-up encounters were included. The likelihood of compliance with follow-up care practices increased significantly (odds ratio 1.15, 95% confidence interval 1.10, 1.19). Mean monthly peritonitis rates significantly decreased from 0.63 episodes per patient year (95% confidence interval 0.43, 0.92) prelaunch to 0.42 (95% confidence interval 0.31, 0.57) at 36 months postlaunch. A sensitivity analysis confirmed that as mean follow-up compliance increased, peritonitis rates decreased, reaching statistical significance at 80% at which point the prelaunch rate was 42% higher than the rate in the months following achievement of 80% compliance. In its first 3 years, the SCOPE Collaborative has increased the implementation of standardized follow-up care and demonstrated a significant reduction in average monthly peritonitis rates.

Immunogenicity of Human Papillomavirus Recombinant Vaccine in Children with CKD.

BACKGROUND AND OBJECTIVES: There is a disproportionate burden of human papillomavirus (HPV) -related genital tract disease in patients with CKD and kidney transplantation; therefore, the potential effect of the quadrivalent HPV vaccine (Gardasil; Merck GmbH, Darmstadt, Germany) is profound. Immune abnormalities associated with CKD and immunosuppression may prevent optimal vaccine response. Our objective was to determine antibody response to the HPV vaccine in adolescent girls with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This cohort study conducted from 2008 to 2012 included 57 girls aged 9-21 years old with CKD (n=25), on dialysis (n=9), or with status postkidney transplantation (n=23) who received the standard three-dose vaccine series of the HPV vaccine recruited from two pediatric nephrology clinics. Antibody levels to HPV genotypes 6, 11, 16, and 18 were measured before vaccine dose 1 (baseline), <12 months after vaccine dose 3 (blood draw 2), and ≥12 months after vaccine dose 3 (blood draw 3). Seropositivity was defined as antibody level above an established threshold for each HPV genotype. Not all participants completed three blood draws. RESULTS: Antibody response to all four HPV genotypes was 100% in the CKD and dialysis groups with samples drawn at <12 and ≥12 months after dose 3 of the HPV vaccine. Among patients with transplants, the percentages of patients achieving seropositivity were significantly lower at blood draw 2 for HPV genotypes 6 (63.6%; P=0.003), 11 (63.6%; P=0.003), and 18 (72.7%; P=0.02) and blood draw 3 for HPV genotypes 6 (62.5%; P=0.02), 11 (50%; P=0.001), 16 (75%; P=0.04), and 18 (50%; P=0.001). CONCLUSIONS: Antibody response to the quadrivalent recombinant HPV vaccine was robust and sustained in girls and young women with CKD and on dialysis. A less robust response to the vaccine was observed among those with a kidney transplant. Additional study is needed to determine if vaccination before kidney transplantation or an alternative vaccination regimen would benefit transplant recipients.

Complete Remission in the Nephrotic Syndrome Study Network.

BACKGROUND AND OBJECTIVES: This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled adults and children with proteinuria ≥0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC) <0.3 g/g with preserved native kidney function and (2) ESRD. Continuous variables are reported as median and interquartile range (IQR; 25th, 75th percentile). Cox proportional hazards modeling was used to assess factors associated with CRever. RESULTS: We enrolled 441 patients: 116 (27%) had MCD, 142 (32%) had FSGS, 66 (15%) had membranous nephropathy, and 117 (27%) had other glomerulopathy. The baseline UPC was 4.1 g/g (IQR, 1.9, 7.7) and the eGFR was 81 ml/min per 1.73 m(2) (IQR, 50, 105). Median duration of observation was 19 months (IQR, 11, 30). CRever occurred in 46% of patients, and 4.6% progressed to ESRD. Multivariate analysis demonstrated that higher prebiopsy proteinuria (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.5) and pathology diagnosis (FSGS versus MCD; hazard ratio, 0.2; 95% confidence interval, 0.1 to 0.5) were inversely associated with CRever. The effect of immunosuppressive therapy on remission varied by pathology diagnosis. CONCLUSIONS: In NEPTUNE, the high frequency of other pathology in proteinuric patients affirms the value of the diagnostic kidney biopsy. Clinical factors, including level of proteinuria before biopsy, pathology diagnosis, and immunosuppression, are associated with complete remission.