Intestinal Microbiota in Pediatric Patients with End Stage Renal Disease: A Midwest Pediatric Nephrology Consortium study

Background: End-stage renal disease (ESRD) is associated with uremia and increased systemic inflammation. Alteration of the intestinal microbiota may facilitate translocation of endotoxins into the systemic circulation leading to inflammation. We hypothesized that children with ESRD have an altered intestinal microbiota and increased serum levels of bacterially derived uremic toxins. Methods: Four groups of subjects were recruited: peritoneal dialysis (PD), hemodialysis (HD), post-kidney transplant and healthy controls. Stool bacterial composition was assessed by pyrosequencing analysis of 16S rRNA genes. Serum levels of C-reactive protein (CRP), D-lactate, p-cresyl sulfate and indoxyl sulfate were measured. Results: Compared to controls, the relative abundance of Firmicutes (P = 0.0228) and Actinobacteria (P = 0.0040) was decreased in PD patients. The relative abundance of Bacteroidetes was increased in HD patients (P = 0.0462). Compared to HD patients the relative abundance of Proteobacteria (P = 0.0233) was increased in PD patients. At the family level, Enterobacteriaceae was significantly increased in PD patients (P = 0.0020) compared to controls; whereas, Bifidobacteria showed a significant decrease in PD and transplant patients (P = 0.0020) compared to control. Alpha diversity was decreased in PD patients and kidney transplant using both phylogenetic and non-phylogenetic diversity measures (P = 0.0031 and 0.0003, respectively), while beta diversity showed significant separation (R statistic = 0.2656, P = 0.010) between PD patients and controls. ESRD patients had increased serum levels of p-cresyl sulfate and indoxyl sulfate (P \u3c 0.0001 and P \u3c 0.0001, respectively). The data suggests that no significant correlation exists between the alpha diversity of the intestinal microbiota and CRP, D-lactate, or uremic toxins. Oral iron supplementation results in expansion of the phylum Proteobacteria. Conclusions: Children with ESRD have altered intestinal microbiota and increased bacterially derived serum uremic toxins

Intestinal Microbiota in Pediatric Patients with End Stage Renal Disease: a Midwest Pediatric Nephrology Consortium Study - Raw Sequencing Data and Mapping File

Raw fastq  and mappint files for the samples contained in the paper "Intestinal Microbiota in Pediatric Patients with End Stage Renal Disease: a Midwest Pediatric Nephrology Consortium Stud

Blood Pressure Outcomes in NICU-Admitted Infants with Neonatal Hypertension: A Pediatric Nephrology Research Consortium Study

Objective To describe the blood pressure outcomes of NICU-admitted infants with idiopathic (non-secondary) hypertension (HTN) who were discharged on antihypertensive therapy. Study Design Retrospective ,multicenter study of 14 centers within the Pediatric Nephrology Research Consortium (PNRC). We included all infants with a diagnosis of idiopathic HTN discharged from neonatal intensive care units (NICU) on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into ≤6 months, \u3e6 months – 1 year, and \u3e 1 year). Comparisons between groups were made with chi-squared tests, Fisher’s exact tests, and analysis of variance. Results Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy \u3e1 year after discharge. Conclusions This multicenter study reports that most NICU-admitted infants diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN but should be confirmed prospectively

Blood Pressure Outcomes in NICU-Admitted Infants with Neonatal Hypertension: A Pediatric Nephrology Research Consortium Study

Objective To describe the blood pressure outcomes of NICU-admitted infants with idiopathic (non-secondary) hypertension (HTN) who were discharged on antihypertensive therapy. Study Design Retrospective ,multicenter study of 14 centers within the Pediatric Nephrology Research Consortium (PNRC). We included all infants with a diagnosis of idiopathic HTN discharged from neonatal intensive care units (NICU) on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into ≤6 months, \u3e6 months – 1 year, and \u3e 1 year). Comparisons between groups were made with chi-squared tests, Fisher’s exact tests, and analysis of variance. Results Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy \u3e1 year after discharge. Conclusions This multicenter study reports that most NICU-admitted infants diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN but should be confirmed prospectively

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 \u3c 25%, 25–50%, and \u3e 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 \u3c 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 m 2 /min (IQR − 51 to + 8) at 1 year and − 3 mL/min/1.73 m 2 /year (IQR − 19 to + 6) at latest follow-up. We found no difference in kidney failure at the proposed \u3c 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

Infections Are Associated with Higher Risk of Venous Thromboembolism in Hospitalized Children with Nephrotic Syndrome

Abstract Introduction: Although it is known that children with nephrotic syndrome (NS) are at greater risk for certain complications, the frequency of these complications and predisposing risk factors are poorly defined. In particular, nephrotic syndrome has long been considered a hypercoagulable state. Risk for development of venous thromboembolism (VTE) is known to be increased in the setting of an active infection. The objective of this study was to determine the prevalence of infection and VTE among a cohort of hospitalized children with NS, and the association of these complications on outcomes. Methods: Records of hospitalized children with NS admitted to any of 17 participating pediatric hospitals across North America from 2010-2012 were included. Data including demographics, clinical pattern of NS, renal biopsy results, number of hospitalizations, nephrotoxic medication usage, infection and VTE history were recorded. Descriptive statistics were used to determine prevalence of infection and VTE. Wilcoxon rank sum was used to perform comparisons between groups. Logistic regression analysis was utilized to determine predictors of VTE development. Results: Seven-hundred thirty hospitalizations occurred among 370 children. One-hundred forty-eight children (40%) had at least 1 infection with a total of 211 infectious episodes; 11 (3%) had VTE. Those with infection were more likely to have VTE (p = 0.0457). Infections associated with VTE were C. difficile (1 subject), methicillin sensitive S. Aureus (2), Streptococcus pneumoniae (1), and unknown (3). There were no differences between those with and without infection regarding gender or ethnicity. Those with infection were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008), and steroid resistant NS was more highly associated with infection than all other clinical diagnoses (steroid-sensitive NS, steroid-dependent NS, other) (p = 0.003). The most common types of infections encountered included peritonitis (23%), pneumonia (22%), and bacteremia (16%). Bacterial pathogens (Streptococcus pneumoniae 41%, Escherichia coli 16%, Clostridium difficile 10%) were most commonly identified. Children with VTE, infection, or both, also required significantly more days in hospital. The median hospital stay for those without infection was 5 days vs. 10 in those with infection (p< 0.0001). Similarly, median hospital days for those without VTE were 6 days as compared to 22 in those with VTE (p < 0.0001). Of those with infection, 13% had an ICU stay compared with 3.3% of those without. Those with VTE also had a median of 4 days in the intensive care unit as compared to 0 days in those without VTE (p < 0.0001). In a logistic regression analysis, only the number of ICU days was predictive of the presence of VTE (OR 1.074, 95% CI 1.013 - 1.138). Conclusions: Children with NS who are hospitalized have high rates of infection. While the rate of VTE was not high in this cohort, presence of VTE was associated with infection. Both infection and VTE were associated with longer hospitalizations and intensive care unit stays. Streptococcus pneumoniae remains the most commonly identified bacterial pathogen in children with nephrotic syndrome, though methicillin sensitive S. Aureus was identified in 2 of 11 patients with VTE. Further studies are needed to identify potentially modifiable risk factors that could minimize these complications in this already high risk population. Disclosures No relevant conflicts of interest to declare

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 \u3c 25%, 25–50%, and \u3e 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 \u3c 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 m 2 /min (IQR − 51 to + 8) at 1 year and − 3 mL/min/1.73 m 2 /year (IQR − 19 to + 6) at latest follow-up. We found no difference in kidney failure at the proposed \u3c 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

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

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. 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. 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). 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