Treatment of Recurrent Focal Segmental Glomerulosclerosis in Pediatric Kidney Transplant Recipients: Effect of Rituximab

Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation is a complication that often leads to graft loss. There is no consensus on the optimal treatment of recurrent FSGS. Rituximab, a monoclonal antibody to CD20, may be a useful treatment of this complication. Methods. We report four pediatric cases of recurrent FSGS treated with rituximab and plasmapheresis. Results. Four children (2M/2F), age 15.3 ± 2.6, with recurrent FSGS posttransplant were identified. Four doses of rituximab were administered 171 ± 180 days posttransplant and 114 ± 169 days after the start of plasmapheresis. Three children responded with complete remission, one of whom relapsed after four months. One child had a partial response with a decrease in proteinuria that was not sustained. No adverse side effects were reported during treatment or followup (mean 22.5 months). Conclusions. Rituximab is a safe and well-tolerated ancillary treatment for recurrent FSGS in pediatric patients in conjunction with plasmapheresis

The prevalence and outcomes of hyponatremia in children with COVID-19 and multisystem inflammatory syndrome in children (MIS-C)

IntroductionTo assess the prevalence of hyponatremia among pediatric patients with coronavirus disease 2019 (COVID-19) and Multisystem Inflammatory Syndrome in Children (MIS-C) and determine if pediatric hyponatremia was associated with an increased length of stay, higher rates of mechanical ventilation, and/or elevated inflammatory markers on admission as compared to eunatremic patients.MethodsElectronic health records were retrospectively analyzed for 168 children less than 18 years old with COVID-19 or MIS-C who were admitted to pediatric units within the Northwell Health system. The primary exposure was hyponatremic status (serum sodium <135 mEq/L) and the primary outcomes were length of stay, mechanical ventilation usage and increased inflammatory markers.ResultsOf the 168 children in the study cohort, 95 (56%) were admitted for COVID-19 and 73 (43.5%) for MIS-C. Overall, 60 (35.7%) patients presented with hyponatremia on admission. Patients with hyponatremia had higher rates of intensive care unit admission when compared to eunatremic patients (32/60 [53.3%] vs. 39/108 [36.1%], p = 0.030). In regression models, hyponatremia was not significantly associated with increased length of stay or mechanical ventilation rates. After adjustment for relevant confounders, hyponatremia remained associated with an increased square root CRP (β = 1.79: 95% CI: 0.22–3.36) and lower albumin levels (β = −0.22: 95% CI: −0.42–−0.01).ConclusionHyponatremia is common in pediatric COVID-19 and MIS-C. Hyponatremia was associated with a lower albumin and higher square root CRP levels. This may suggest an association of inflammation with lower serum sodium levels

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 m 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

The impact of disease duration on quality of life in children with nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study

The Patient Reported Outcomes Measurement Information System (PROMIS) II is a prospective study that evaluates patient reported outcomes in pediatric chronic diseases as a measure of health-related quality of life (HRQOL). We have evaluated the influence of disease duration on HRQOL and, for the first time, compared the findings of the PROMIS measures to those of the PedsQL™ 4.0 Generic Scales (PedsQL) from the PROMIS II nephrotic syndrome (NS) longitudinal cohort

Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach

The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multi-center collaborative consortium established to develop a translational research infrastructure for Nephrotic Syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary studies program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy for detailed clinical, histopathologic, and molecular phenotyping at the time of clinically-indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and bi-annually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histologic data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for Nephrotic Syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies

Developmental Origins and Nephron Endowment in Hypertension

Primary hypertension continues to be one of the main risk factors for cardiovascular disease worldwide. A stable intrauterine environment is critical for the future development and health of the fetus. The developing kidney has been found to be especially vulnerable during this time period, and epidemiological studies have demonstrated that an adverse in utero environment is associated with an increased risk of hypertension and chronic kidney disease. Macro- and micronutrient deficiencies as well as exposure to tobacco, alcohol, and certain medications during gestation have been shown to negatively impact nephrogenesis and reduce one’s nephron number. In 1988, Brenner et al. put forth the controversial hypothesis that a reduced nephron complement is a risk factor for hypertension and chronic kidney disease in adulthood. Since then numerous animal and human studies have confirmed this relationship demonstrating that there is an inverse association between blood pressure and nephron number. As our understanding of the developmental programming of hypertension and other non-communicable diseases improves, more effective preventive health measures can be developed in the future

Nephrotic syndrome in children during the COVID-19 pandemic

The COVID-19 pandemic resulted in public health measures and fewer viral infections, which trigger the nephrotic syndrome. Our objectives were to characterize the effect of the COVID-19 pandemic on children with nephrotic syndrome. This single-center retrospective chart review compared children with nephrotic syndrome one year before the pandemic with the first wave of the pandemic. Epidemiologic events, clinical characteristics, and health care utilization were compared using paired t-tests, Fisher’s exact tests and Wilcoxon Rank Sum tests. Among 96 children the mean age was 10.7 ± 5.28 years. The distribution was minimal change disease (16.7%), focal segmental glomerulosclerosis (12.5%), membranous nephropathy (1%) and not biopsied (69.8%). Medication responsiveness was steroid-sensitive (25%), frequently relapsed (54%) and steroid-resistant (20.8%). There were 14 new diagnoses of nephrotic syndrome pre-pandemic and 18 during the pandemic. Fewer relapses during the pandemic were likely due to fewer viral illnesses from public health measures during the pandemic