Age-based risk of end-stage kidney disease in patients with myelomeningocele.

OBJECTIVE: We aimed to quantify end-stage kidney disease (ESKD) risk after infancy in individuals with myelomeningocele (MMC) followed by urology in the modern medical era and to assess if ESKD risk was higher after surgery related to a hostile bladder. METHODS: We retrospectively reviewed patients with MMC followed by urology at our institution born ≥ 1972 (when clean intermittent catheterization was introduced) past 1 year of age (when mortality is highest, sometimes before establishing urology care). ESKD was defined as requiring permanent peritoneal/hemodialysis or renal transplantation. Early surgery related to hostile bladder included incontinent vesicostomy, bladder augmentation, detrusor Botulinum A toxin injection, ureteral reimplantation, or nephrectomy for recurrent urinary tract infections. Survival analysis and proportional hazards regression were used. Sensitivity analyses included: risk factor analysis with only vesicostomy, timing of surgery, including the entire population without minimal follow-up (n = 1054) and only patients with ≥ 5 years of follow-up (n = 925). RESULTS: Overall, 1029 patients with MMC were followed for a median of 17.0 years (49% female, 76% shunted). Seven patients (0.7%) developed ESKD at a median 24.3 years old (5 hemodialysis, 1 peritoneal dialysis, 1 transplantation). On survival analysis, the ESKD risk was 0.3% at 20 years old and 2.1% at 30 years old (Figure). This was ∼100 times higher than the general population (0.003% by 21 years old, p < 0.001). Patients who underwent early surgery for hostile bladder had higher ESKD risk (HR 8.3, p = 0.001, 6% vs. 1.5% at 30 years). On exploratory analyses, gender, birth year, shunt status and wheelchair use were not associated with ESKD risk (p ≥ 0.16). Thirty-year ESKD risk was 10% after early vesicostomy vs. 1.4% among children without one (p = 0.001). Children undergoing bladder surgery between 1.5 and 5 years old had a higher risk of ESKD. No other statistically/clinically significant differences were noted. COMMENT: Patients with MMC remain at risk of progressive renal damage throughout life. We relied on the final binary ESKD outcome to quantify this risk, rather than imprecise glomerular filtration rate formulas. Analysis was limited by few people developing ESKD, inconsistent documentation of early urodynamic findings and indications for bladder-related surgery. CONCLUSIONS: While ESKD is relatively uncommon in the MMC population receiving routine urological care, affecting 2.1% of individuals in the first 3 decades, it is significantly higher than the general population. Children with poor bladder function are likely at high risk, underlining the need for routine urological care, particularly in adulthood.

Factors affecting dialysis duration in children with Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome.

BACKGROUND: Predicting disease severity can be informative for management of HUS. Dialysis requirement, volume depletion, elevated white blood cell counts, very young age, and use of antimotility agents are known factors associated with severe HUS. METHODS: A retrospective cohort analysis was performed to identify factors associated with dialysis duration using electronic medical record and chart review of 76 children ≤ 18 years of age at presentation with STEC-HUS identified through billing data from July 2008 to April 2020 at James Whitcomb Riley Hospital for Children, Indiana University, Indiana. RESULTS: Novel findings associated with prolonged dialysis duration were age ≥ 6 years old at presentation (p = 0.041) and lack of drop in platelets below 60,000/mm3 anytime during the illness (p = 0.015). In addition, children with NSAID exposure trended longer on dialysis: 15 days with vs. 10 days without (p = 0.117). Known risk factors for severe disease including elevated peak white blood cell (WBC) count and higher hematocrit at presentation were also associated with longer dialysis duration: children with peak WBC > 20,000/mm3 were on dialysis for 15 vs. 9.5 days (p = 0.002) and in children on dialysis ≥ 14 days hematocrit at presentation was 29.6% vs. 24.2% (p = 0.03). Children requiring dialysis for 20 days or longer were more likely to be on anti-hypertensive medications (p = 0.025) and have chronic kidney disease at 12-month follow up (p = 0.044). CONCLUSIONS: Age ≥ 6, elevated WBC count > 20,000/mm3, higher hematocrit at presentation, lack of drop in platelets to < 60,000/mm3, and possibly NSAID exposure during illness are associated with longer dialysis duration in STEC-HUS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Thalamocortical functional connectivity in infants with prenatal opioid exposure correlates with severity of neonatal opioid withdrawal syndrome.

PURPOSE: Prenatal opioid exposure (POE) is a growing public health concern due to its associated adverse outcomes including neonatal opioid withdrawal syndrome (NOWS). The aim of this study was to assess alterations in thalamic functional connectivity in neonates with POE using resting-state functional magnetic resonance imaging (rs-fMRI) and identify whether these altered connectivity measures were associated with NOWS severity. METHODS: In this prospective, IRB-approved study, we performed rs-fMRI in 19 infants with POE and 20 healthy control infants without POE. Following standard pre-processing, we performed seed-based functional connectivity analysis with the right and left thalamus as the regions of interest. We performed post hoc analysis in the prenatal opioid exposure group to identify associations of altered thalamocortical connectivity with severity of NOWS. P value of < .05 was considered statistically significant. RESULTS: There were several regions of significantly altered thalamic to cortical functional connectivity in infants with POE compared to the healthy infants. Distinct regions of thalamocortical functional connectivity correlated with maximum modified Finnegan score. Association between thalamocortical connectivity and severity of NOWS was nominally modified by maternal psychological conditions and polysubstance use. CONCLUSION: Our findings reveal prenatal opioid exposure-related alterations in thalamic functional connectivity in the infant brain that are correlated with severity of NOWS. Future studies may benefit from evaluation of thalamocortical resting state functional connectivity in infants with POE to help  stratify risk of long term neurodevelopmental outcomes.