Sex, Acute Kidney Injury, and Age: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Animal models of kidney disease suggest a protective role for female sex hormones but in humans, some authorities assert that female sex is a risk factor for acute kidney injury (AKI). To better understand the risk of AKI, we studied the strength of association between sex and AKI incidence in hormonally distinct age groups across the life span. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: All patients hospitalized in the Montefiore Health System between 10/15/2015 and 1/1/2019, excluding those with kidney failure or obstetrics diagnoses. EXPOSURE: Male versus female sex. OUTCOMES: Acute kidney injury (AKI) occurring during hospitalization based on KDIGO definitions. ANALYTICAL APPROACH: Generalized Estimating Equation logistic regression adjusted for comorbidities, socio-demographic factors, and severity of illness. Analyses were stratified into 3 age categories, 6 months to ≤16 years, age >16 years - <55 years, and age ≥55 years. RESULTS: A total of 132,667 individuals were hospitalized a total of 235,629 times. The mean age was 55.2 (SD 23.8) years. The counts (%) of hospitalizations for women were 129,912 (55%). Hospitalization counts (%) among Black and Hispanic patients were 71,834 (30.5%) and 24,199 (10.3%), respectively. AKI occurred in 53,926 (22.9%) hospitalizations. In adjusted models, there was a significant interaction between age and sex (p<0.001). Boys and men had higher risk of AKI across all age groups, an association more pronounced in the age group >16 years to <55 years in which the OR for men was 1.7 (95% CI, 1.6-1.8). This age-based pattern remained consistent across prespecified types of hospitalizations. In a sensitivity analysis, women older than 55 years who received prescriptions for estrogen had lower odds of AKI than those without prescriptions. LIMITATIONS: Residual confounding. CONCLUSION: The greatest relative risk of AKI for males occurred during ages >16 to <55 years. The lower risk among post-menopausal women receiving supplemental estrogen supports a protective role for female sex hormones.

Derivation and Validation of an Optimal Neutrophil Gelatinase-Associated Lipocalin Cutoff to Predict Stage 2/3 Acute Kidney Injury (AKI) in Critically Ill Children.

Introduction: Acute kidney injury (AKI) defined by changes in serum creatinine (SCr), or oliguria is associated with increased morbidity and mortality in children who are critically ill. We derived and validated a clinical cutoff value for urine neutrophil gelatinase-associated lipocalin (NGAL), in a prospective multicenter study of children who were critically ill. We report the clinical performance of urine NGAL (uNGAL) to aid in pediatric AKI risk assessment. Methods: Eligible subjects were aged ≥ 90 days to < 22 years, admitted to an intensive care unit (ICU), and had 1 or more of the following: mechanical ventilation, vasoactive medication administration, solid organ or bone marrow transplantation, or hypotension within 24-hours of admission. uNGAL was assessed within 24-hours of admission. The primary outcome was SCr-based stage 2/3 AKI presence at 48- to 72-hours. Results: Twenty-five (12.3%) derivation study patients had stage 2/3 AKI at 48- to 72-hours. uNGAL concentration of 125 ng/ml was the optimal cutoff. Forty-seven (9.1%) validation study patients had stage 2/3 AKI at 48- to 72-hours. The area under the curve of a receiver operator characteristics curve (AUC-ROC) for uNGAL performance was 0.83 (95% confidence interval [CI]: 0.77-0.90). Performance characteristics were sensitivity 72.3% (95% CI: 57.4%-84.4%), specificity 86.3% (95% CI: 82.8%-89.3%), positive predictive value 34.7% (95% CI: 28.5%-41.5%), and negative predictive value 96.9% (95% CI: 95.1%-98.0%). Conclusion: These prospective, pediatric, multicenter studies demonstrate that uNGAL in the first 24-hours performs very well to predict Kidney Disease Improving Global Outcomes (KDIGO) stage 2/3 AKI at 48- to 72-hours into an ICU course. We suggest that a uNGAL cut point of 125 ng/ml can aid in the risk assessment for stage 2/3 AKI persistence or development.

Caffeine intake and cardiometabolic risk factors in adolescents in the United States.

BACKGROUND: In adults, caffeine has protective effects against kidney dysfunction and type 2 diabetes mellitus (T2DM) but increases the risk of acute blood pressure (BP) elevation and dyslipidemia. These relationships are unclear in adolescents. This study aimed to determine the association between caffeine intake and markers of childhood cardiometabolic risk, hypothesizing that higher caffeine intake would be associated with elevated BP and dyslipidemia but improved kidney function and insulin sensitivity. METHODS: Adolescents ages 13-17 who participated in the National Health and Nutritional Examination Survey (NHANES) from 2011 to 2018 and completed 24-h dietary recalls were included. Logistic and linear regression models were used to analyze cross-sectional associations between caffeine and cardiometabolic risk factors. RESULTS: The mean participant age was 15.0 years, with a sex distribution of 49.9% male and 50.1% female. In fully adjusted regression models, higher caffeine intake was not associated with any changes in BP (OR = 0.78, 95%CI [0.52,1.16], p = 0.21), dyslipidemia (OR = 0.91, 95%CI [0.65,1.27], p = 0.57), glomerular hyperfiltration (OR = 1.01, 95%CI [0.60,1.71], p = 0.96), albuminuria (OR = 0.94, 95%CI [0.45,1.98], p = 0.87), or insulin resistance (OR = 1.15, 95%CI [0.85,1.56], p = 0.36). CONCLUSION: Contrary to its cardiometabolic effects in adults, caffeine intake was not associated with an increased or reduced risk of kidney dysfunction, T2DM, hypertension, or dyslipidemia in adolescents. IMPACT: Although the effects of caffeine intake on cardiometabolic risk have been well defined in adults, data exploring its impact on adolescent cardiovascular and metabolic function is limited. The goal of this study was to understand the relationship between caffeine intake and markers of childhood cardiometabolic risk. Unlike its established effects in adults, caffeine consumption showed no association with markers of cardiometabolic disease, such as kidney dysfunction, type 2 diabetes mellitus, blood pressure, dyslipidemia, or hyperuricemia in adolescents. These findings offer novel insight into the effects of caffeine on cardiometabolic function in adolescents, which may guide clinical recommendations for at-risk patients.

TikTok and pediatric nephrology: content quality assessment of videos related to pediatric kidney disease and kidney transplant.

BACKGROUND: Social media platforms such as TikTok™ are key sources of health information for young patients and caregivers. Misinformation is prevalent on TikTok™ across healthcare fields, which can perpetuate false beliefs about medical care. Limited data exists on the reliability of pediatric nephrology TikTok™ content. This study aimed to describe the quality of medical content of TikTok™ Videos (TTVs), related to pediatric kidney disease and transplant. METHODS: TTVs were selected using specific search terms and categorized into pediatric kidney disease and kidney transplant, excluding duplicate and adult-related content. The top 100 TTVs in each category, based on views, were analyzed. TTV characteristics were stratified by account type (physician, non-physician healthcare professional (HCP), non-HCP) and video aim (personal story, education, entertainment). DISCERN scoring, a validated questionnaire evaluating health information reliability, was conducted by 4 independent raters. Inter-rater reliability was assessed using a 2-way random effects model, and differences between content creator types were evaluated using one-way ANOVA and post-Hoc Tukey test. RESULTS: TTVs had a total of 12.5 million likes and 113.1 million views. Over 70% of videos were created by non-HCPs (n = 147/200). DISCERN scoring revealed low reliability of medical information across content creator types. TTVs created by physicians and non-physician HCPs about kidney disease had significantly higher mean DISCERN scores compared to those created by non-HCPs (2.85, p < 0.001 and 2.48, p = 0.005, respectively). CONCLUSIONS: Educators within the pediatric nephrology community must keep in mind the lack of reliability of medical information available on TikTok™ and coordinate collective efforts to consider utilizing TikTok™ for patient education.

The association between sleep duration and cardiometabolic risk among children and adolescents in the United States (US): A NHANES study.

PURPOSE: This work aims to assess the association of sleep duration with cardiometabolic risk (adiposity, blood pressure, lipids, albuminuria and A1C) and to investigate lifestyle factors (physical activity, light exposure, caffeine consumption and sugar consumption) associated with sleep duration in children. METHODS: A nationally representative sample of 3907 children ages 6-17 years enrolled in NHANES from 2011 to 2014 was included in this cross-sectional study. Sleep duration was defined as the daily average time spent sleeping over 7 days as measured by a physical activity monitor (PAM). Participants without valid sleep data for ≥95% of the study were excluded. Regression models were adjusted for age, sex, race, body mass index (BMI) Z score, physical activity and light exposure. RESULTS: In adjusted regression models, longer sleep duration was associated with lower systolic blood pressure index (ß = -3.63 * 10-5, 95% CI -6.99 * 10-5, -2.78 * 10-6, p = 0.035) and BMI Z score (ß = -0.001, 95% CI -0.001, 0.000, p = 0.002). In logistic regression models, longer sleep duration was associated with lower odds of obesity (OR = 0.998, 95% CI 0.997, 0.999, p < 0.001) and overweight status (OR = 0.998, 95% CI 0.997, 0.999, p = 0.004). Greater light exposure (ß = 6.64 * 10-5, 95% CI 3.50 * 10-5, 9.69 * 10-5, p < 0.001) and physical activity (ß = 0.005, 95% CI 0.004, 0.006, p < 0.001) were associated with longer sleep. CONCLUSION: Longer sleep duration was associated with lower blood pressure and adiposity measures in children. Improving sleep quality by increasing physical activity and light exposure in childhood may decrease the lifetime risk of cardiometabolic disease.

Anterior and posterior ischemic optic neuropathy in a child with focal segmental glomerulosclerosis on hemodialysis.

BACKGROUND: Ischemic optic neuropathy (ION) is exceedingly rare in children on dialysis, resulting from poor perfusion of the optic nerve, and presents as sudden acute painless vision loss. CASE-DIAGNOSIS/TREATMENT: We report the case of a 3-year-old male with stage 5 chronic kidney disease (CKD 5) due to focal segmental glomerulosclerosis (FSGS) status post-bilateral nephrectomy on chronic hemodialysis who had acute loss of vision several hours after a hemodialysis session. Earlier that day, he had a drop in blood pressure intra-dialysis to 89/67 mmHg, with at home blood pressures ranging 90/60 to 150/100 mmHg. The patient was treated with tight blood pressure control to maintain blood flow and prevent blood pressure lability, received high-dose corticosteroids with a corticosteroid taper, and placed on high-dose erythropoietin for neuroprotective effect. He regained partial vision beginning approximately 1 month after presentation. CONCLUSIONS: The exact cause of our patient's simultaneous bilateral anterior and posterior ION, confirmed via MRI and fundoscopic examination, is unclear; however, is likely secondary to a combination of fluctuating blood pressure, anemia, anephric status, and hemodialysis. This highlights the need for close blood pressure monitoring, management of anemia, and more diligent ophthalmologic screening in pediatric patients on chronic hemodialysis.

Reclassification of Adolescent Ambulatory Prehypertension and Unclassified Blood Pressures by 2022 American Heart Association Pediatric Ambulatory Blood Pressure Monitoring Guidelines.

OBJECTIVE: To describe the epidemiology of reclassification of prehypertensive and unclassified adolescents by 2022 American Heart Association pediatric ambulatory blood pressure monitoring (ABPM) guidelines, and to evaluate the association of the new diagnostic categories with left ventricular hypertrophy (LVH). STUDY DESIGN: A single-center, retrospective review of ABPM reports from adolescents 13-21 years old, from 2015 through 2022, was performed. Adolescents with prehypertension or unclassified by 2014 guidelines were reclassified by 2022 definitions. Logistic regression models evaluated the association of reclassification phenotypes with LVH. RESULTS: A majority of prehypertensive adolescents reclassified to hypertension (70%, n = 49/70). More than one-half (57%, n = 28/49) of the hypertension was isolated nocturnal hypertension, and 80% was systolic hypertension. Reclassification to hypertension was more common in males. The majority (55.6%) of unclassified adolescents were reclassified to normotension. No demographic or clinical variables were associated with reclassification categories. LVH was not associated with hypertension in the reclassified prehypertensive or unclassified groups. CONCLUSIONS: The 2022 ABPM guidelines clearly define blood pressure phenotypes. However, reclassification to hypertension was not associated with an increased odds of LVH. Because most prehypertensive adolescents reclassified as hypertensive by nighttime BPs alone, this study highlights the lowered threshold for nocturnal hypertension. Prospective studies in larger, well-defined cohorts are needed to describe better the predictive value of 2022 BP phenotypes for target organ damage.

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

Introduction: To 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. Methods: Electronic 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. Results: Of 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 (ß = 1.79: 95% CI: 0.22-3.36) and lower albumin levels (ß = -0.22: 95% CI: -0.42--0.01). Conclusion: Hyponatremia 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.

Reclassification of Adolescent Ambulatory Prehypertension and Unclassified Blood Pressures by 2022 American Heart Association Pediatric Ambulatory Blood Pressure Monitoring Guidelines.

Background: The 2022 American Heart Association (AHA) pediatric ambulatory blood pressure monitoring (ABPM) guidelines eliminated the prehypertension phenotype and blood pressure loads in ABPM interpretation criteria. Adolescents who were prehypertensive or unclassified according to the 2014 AHA pediatric ABPM guidelines will be reclassified as having hypertension or normotension. The epidemiology and association of reclassification phenotype with target organ damage (TOD) is not yet known. Methods: A single center retrospective review of adolescents ages 13-21 years old between 2015-2022 was performed. Adolescents diagnosed with prehypertension or unclassified by the 2014 AHA pediatric ABPM guidelines were reclassified by the 2022 definitions. Logistic regression models adjusted for body mass index z-score evaluated the association of reclassification phenotype with left ventricular hypertrophy (LVH). Results: Among 88 adolescents with prehypertension, 68% (N = 60) were reclassified as hypertensive. The majority (58%, N = 35) of hypertensive reclassification was based on isolated nocturnal blood pressures ≥ 110/65 mmHg. Taller males were more likely to reclassify as hypertensive. Adolescents reclassified as hypertensive had a greater-than-six-fold increased odds of LVH in adjusted models [OR 6.4 95%CI 1.2-33.0, p = 0.027]. Of 40 adolescents with unclassified blood pressures, 37.5% (N = 15) reclassified to normotension. There were no significant clinical or demographic variables associated with reclassification category nor was there an association with LVH. Conclusions: The new ABPM guidelines effectively reclassify adolescents who were previously prehypertensive as normotensive or hypertensive based on risk of TOD. Further studies are needed to describe the long-term outcomes of ABPM phenotypes with the implementation of these guidelines.

Association Between Dietary Fiber Intake and Cardiometabolic Risk Factors in Adolescents in the United States.

OBJECTIVE: To determine the association between dietary fiber intake and markers of cardiometabolic risk in adolescents, with blood pressure (BP) as the primary outcome of interest and secondary outcome measures including other established markers of childhood cardiometabolic risk, such as obesity, lipids, albuminuria, estimated glomerular filtration rate (eGFR), and uric acid. STUDY DESIGN: Dietary fiber intake was assessed by two 24-hour dietary recall interviews, which were averaged and corrected for body weight. Logistic and linear regression models were used to analyze the cross-sectional association between dietary fiber and cardiometabolic markers. Participants aged 13-17 years in the National Health and Nutritional Examination Survey 2009-2018 who completed a 24-hour dietary recall survey were included. Exclusion criteria included pregnancy, small for gestational age status, and history of major health comorbidities. RESULTS: In fully adjusted regression models, low dietary fiber intake was significantly associated with greater diastolic blood pressure (ß = -13.29; 95% CI, -20.66 to -5.93), body mass index z-score (ß = -0.91; 95% CI, -1.47 to -0.34), and uric acid (ß = -0.80; 95% CI, -1.44 to -0.16). CONCLUSIONS: The association found between low dietary fiber intake and poor childhood cardiometabolic risk markers indicate a need for prospective studies using fiber intake as a dietary intervention in childhood and as a tool for prevention of many chronic conditions.

Acute kidney injury post-abdominal surgery in infants: implications for prevention and management.

Acute kidney injury (AKI) is common in critically ill infants and is associated with long-term sequelae including hypertension and chronic kidney disease. The etiology of AKI in infants is multifactorial. There is robust literature highlighting the risk of AKI after cardiothoracic surgery in infants. However, risk factors and outcomes for AKI in infants after abdominal surgery remains limited. This article reviews the epidemiology and association of abdominal surgery with postoperative AKI and suggests methods for AKI management and prevention. Postoperative AKI may result from hemodynamic shifts, hypoxia, exposure to nephrotoxic medications, and inflammation. Infants in the intensive care unit after intraabdominal surgeries have a unique set of risk factors that predispose them to AKI development. Prematurity, sepsis, prolonged operation time, emergent nature of the procedure, and diagnosis of necrotizing enterocolitis increase risk of AKI after intrabdominal surgeries. Prevention, early diagnosis, and management of AKI post-abdominal surgery is imperative to clinical practice. Close monitoring of urine output, serum creatinine, and fluid status is necessary in infants after abdominal surgery. A recent study suggests elevated levels of a urinary biomarker, neutrophil gelatinase-associated lipocalin (NGAL), 24 h after an abdominal procedure may improve early prediction of AKI. Identification of risk factors, avoidance of nephrotoxic medications, careful fluid balance, early detection of AKI, and maintenance of hemodynamic stability is imperative to potentially prevent and/or mitigate AKI.

Ambulatory Blood Pressure Monitoring in Pediatrics, an Update on Interpretation and Classification of Hypertension Phenotypes.

PURPOSE OF REVIEW: This review highlights the major changes reflected in the 2022 American Heart Association (AHA) Scientific Statement on Ambulatory Blood Pressure Monitoring (ABPM) in Children and Adolescents with a specific focus on the newly defined phenotypes of hypertension and their epidemiology and associated outcomes. RECENT FINDINGS: The 2022 AHA guidelines' most notable changes include the following: (1) alignment of blood pressure (BP) thresholds with the 2017 American Academy of Pediatrics (AAP) clinical practice guidelines, 2017 American College of Cardiology (ACC)/AHA hypertension guidelines, and 2016 European Society of Hypertension (ESH) pediatric recommendations; (2) expansion of the use of ABPM to diagnose and phenotype pediatric hypertension in all pediatric patients; (3) removal of BP loads from diagnostic criteria; and (4) simplified classification of new hypertension phenotypes to prognosticate risks and guide clinical management. Recent studies suggest that utilizing the 2022 AHA pediatric ABPM guidelines will increase the prevalence of pediatric ambulatory hypertension, especially for wake ambulatory hypertension in older, taller males and for nocturnal hypertension in both males and females ≥ 8 years of age. The new definitions simplify the ambulatory hypertension criteria to include only the elements most predictive of future health outcomes, increase the sensitivity of BP thresholds in alignment with recent data and other guidelines, and thus make hypertension diagnoses more clinically meaningful. This guideline will also aid in the transition of adolescents and young adults to adult medical care. Further studies will be necessary to study ambulatory BP norms in a more diverse pediatric population and evaluate the impact of these guidelines on prevalence and future outcomes.

Perceived family impact and coping mechanisms of caregivers of children with nephrotic syndrome.

BACKGROUND: Pediatric chronic disease impacts the affected child and their family structure. There is limited literature investigating the psychosocial impact of nephrotic syndrome on families. METHODS: Caregivers of children with nephrotic syndrome completed two validated surveys: (1) Impact on Family (IOF) that evaluates the family impact (degree to which family is affected by a pediatric chronic illness) and (2) Coping Health Inventory for Parents (CHIP) that examines the coping patterns used by caregivers. Linear regression models were utilized to determine predictors of perceived family impact and coping patterns. RESULTS: Seventy-five caregivers of a child with nephrotic syndrome completed the surveys. On a scale from low impact to significant impact to very serious impact, results indicated that nephrotic syndrome had a significant impact on families (mean revised IOF total score 33.04 ± 9.38). Families in the steroid-resistant nephrotic syndrome (SRNS) group reported a higher financial impact compared to the steroid-sensitive nephrotic syndrome (SSNS) group (p = 0.03). Families in the frequently relapsing group (FRNS) reported a higher impact on the caregiver's ability to cope with the child's condition compared to the SRNS group (p = 0.02). Tacrolimus use was associated with increasing the perceived family impact (ß = 4.76, p = 0.046). CHIP scores indicated that caregivers did not cope well with family integration (component I) but coped well with social support (component II) and communication (component III). CONCLUSIONS: Childhood nephrotic syndrome has a significant overall perceived impact on the family, and caregivers did not cope well regarding strengthening their family life. These findings can be used as outcome measures for future intervention studies to find solutions that would decrease the perceived family burden. A higher resolution version of the Graphical abstract is available as Supplementary information.

Associations of Dysnatremia with COVID-19 Status and Mortality.

Background: In patients without COVID-19, dysnatremia is associated with mortality. These relationships are not well established in patients with COVID-19. We tested the hypotheses that patients with COVID-19 were more likely to have dysnatremia than those without COVID-19 and that, among those with COVID-19, dysnatremia is associated with mortality. Methods: We conducted a retrospective observational study of patients admitted to a tertiary care center in the Bronx, New York, during the COVID-19 surge from March 11 to April 26, 2020. Using multinomial logistic regression models, we compared the prevalence of hypernatremia (serum sodium ≥150 mEq/L) and hyponatremia (serum sodium <130 mEq/L) on admission between patients with and without COVID-19. Among patients with COVID-19, we used Cox proportional hazards models to examine the association of dysnatremia with mortality. Results: Compared with those without COVID-19 (n=1265), patients with COVID-19 (n=3345) had a higher prevalence of hypernatremia (7% versus 4%, P<0.001) and hyponatremia (7% versus 6%, P=0.04). In adjusted models, COVID-19-positive patients had a higher likelihood of having hypernatremia (adjusted odds ratio=1.87, 95% CI, 1.3 to 2.57, P=0.001) compared with COVID-19-negative patients, whereas the association between hyponatremia and COVID-19 status was no longer significant (P=0.06). Among patients with COVID-19, 775 (23%) died after a median follow-up of 17 days (IQR 7-27 days). Among nonsurvivors, 15% had hypernatremia and 8% had hyponatremia on admission. Hypernatremia was associated with a higher risk of mortality (adjusted hazard ratio=1.28, 95% CI, 1.01 to 1.63, P=0.04) compared with patients with eunatremia. Conclusions: In patients hospitalized during the spring 2020 COVID-19 surge, COVID-19 status was associated with hypernatremia on admission. Among patients with COVID-19, hypernatremia was associated with higher mortality. Hypernatremia may be a potential prognostic marker for mortality in COVID-19 patients.

COL4A4 variant recently identified: lessons learned in variant interpretation-a case report.

BACKGROUND: Alport syndrome is a hereditary kidney disease characterized by hematuria and proteinuria. Although there have been reports of autosomal dominant COL4A4 variants, this is likely an underdiagnosed condition. Improved access to affordable genetic testing has increased the diagnosis of Alport syndrome. As genetic testing becomes ubiquitous, it is imperative that clinical nephrologists understand the benefits and challenges associated with clinical genetic testing. CASE PRESENTATION: We present a family of Mexican descent with a heterozygous COL4A4 variant (c.5007delC, ClinVar accession numbers: SCV001580980.2, SCV001993731.1) not previously discussed in detail in the literature. The proband received a biopsy diagnosis suggestive of Fabry disease 18 years after she first developed hematuria and progressed to chronic kidney disease stage III. One year later, the proband was provisionally diagnosed with Alport syndrome after a variant of uncertain significance in the COL4A4 gene was identified following targeted family variant testing of her daughter. Upon review of the medical histories of the proband's children and niece, all but one had the same variant. Of the four with the variant, three display clinical symptoms of hematuria, and/or proteinuria. The youngest of the four, only months old, has yet to exhibit clinical symptoms. Despite these findings there was a considerable delay in synthesizing this data, as patients were tested in different commercial genetic testing laboratories. Subsequently, understanding this family's inheritance pattern, family history, and clinical symptoms, as well as the location of the COL4A4 variant resulted in the upgrade of the variant's classification. Although the classification of this variant varied among different clinical genetic testing laboratories, the consensus was that this variant is likely pathogenic. CONCLUSIONS: This COL4A4 variant (c.5007delC) not yet discussed in detail in the literature is associated with Alport syndrome. The inheritance pattern is suggestive of autosomal dominant inheritance. This report highlights the intricacies of variant interpretation and classification, the siloed nature of commercial genetic testing laboratories, and the importance of a thorough family history for proper variant interpretation. Additionally, the cases demonstrate the varied clinical presentations of Alport syndrome and suggest the utility of early screening, diagnosis, monitoring, and treatment.

Influence of Donor Race and Donor-recipient Race-matching on Pediatric Kidney Transplant Outcomes.

Existing literature has demonstrated the significant relationship between race and kidney transplant outcomes; however, there are conflicting and limited data on the influence of donor race or donor-recipient race-matching on pediatric kidney transplant outcomes. Methods: Analysis included kidney-only transplant recipients between ages 2 and 17 from 2000 to 2017 enrolled in the Organ Procurement and Transplantation Network and their associated donors. Multivariable regression models were used to compare outcomes by donor race and donor-recipient race-matched status. Results: Of the total 7343 recipients, 4458 (60.7%) recipients received a kidney from a White donor, 1009 (13.7%) from a Black donor, 1594 (21.7%) from Hispanic donor, and 169 (4.1%) from an Asian donor; 4089 (55.7%) were race-matched. No donor races were significantly associated with transplant outcomes (all P > 0.05). Race-matched status was not associated with graft failure (hazard ratio, 1.03; 95% confidence interval [CI] = 0.89-1.2; P = 0.68), mortality (hazard ratio, 1.1; 95% CI, 0.79-1.53; P = 0.56), acute rejection at 1 y (odds ratio, 0.94; 95% CI, 0.77-1.15; P = 0.53), or delayed graft function (odds ratio, 1.02; 95% CI, 0.80-1.29; P = 0.91). Conclusions: Neither donor race nor race-matched status is associated with better transplant outcomes. Further studies are necessary to confirm the impact of donor race and race-matching more fully on pediatric kidney transplant outcomes.

Association of early dysnatremia with mortality in the neonatal intensive care unit: results from the AWAKEN study.

OBJECTIVE: To determine the association of dysnatremia in the first postnatal week and risk of acute kidney injury (AKI) and mortality. STUDY DESIGN: A secondary analysis of 1979 neonates in the AWAKEN cohort evaluated the association of dysnatremia with (1) AKI in the first postnatal week and (2) mortality, utilizing time-varying Cox proportional hazard models. RESULT: Dysnatremia developed in 50.2% of the cohort and was not associated with AKI. Mortality was associated with hyponatremia (HR 2.15, 95% CI 1.07-4.31), hypernatremia (HR 4.23, 95% CI 2.07-8.65), and combined hypo/hypernatremia (HR 6.39, 95% CI 2.01-14.01). In stratified models by AKI-status, hypernatremia and hypo/hypernatremia increased risk of mortality in neonates without AKI. CONCLUSION: Dysnatremia within the first postnatal week was associated with increased risk of mortality. Hypernatremia and combined hypo/hypernatremia remained significantly associated with mortality in neonates without AKI. This may reflect fluid strategies kidney injury independent of creatinine and urine-output defined AKI, and/or systemic inflammation.

Management of severe hyponatremia with low-dose continuous kidney replacement therapy and peripheral D5W in an infant with acute kidney injury.

We report a 7-month-old female infant who presented with anuric acute kidney injury and severe hyponatremia (serum sodium 110 mEq/L). The patient was treated with low-dose continuous kidney replacement therapy (CKRT), that is, 85% of total clearance dose divided equally between normonatric (Na 140 mEq/L) replacement and dialysate fluids. The remaining 15% of the clearance was provided by peripheral infusion of dextrose 5% (D5W). The patient's sodium was maintained between 119 mEq/L and 121 mEq/L for the first 24 hours of CKRT. Over the next 2 days, the rate of D5W infusion was slowly decreased while replacement and dialysis flow rates were proportionately increased. Serum sodium was normalised by day 2 of the therapy. The patient had no neurologic sequelae associated with this therapy.

Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19.

This study describes the incidence, associated clinical characteristics and outcomes of acute kidney injury in a pediatric cohort with COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C). We performed a retrospective study of patients 18 years of age and under admitted to four New York hospitals in the Northwell Health System interned during the height of the COVID-19 pandemic, between March 9 and August 13, 2020. Acute kidney injury was defined and staged according to Kidney Disease: Improving Global Outcomes criteria. The cohort included 152 patients; 97 acute-COVID-19 and 55 with MIS-C associated with COVID-19. Acute kidney injury occurred in 8 with acute-COVID-19 and in 10 with MIS-C. Acute kidney injury, in unadjusted models, was associated with a lower serum albumin level (odds ratio 0.17; 95% confidence interval 0.07, 0.39) and higher white blood cell counts (odds ratio 1.11; 95% confidence interval 1.04, 1.2). Patients with MIS-C and acute kidney injury had significantly greater rates of systolic dysfunction, compared to those without (80% vs 49%). In unadjusted models, patients with acute kidney injury had 8.4 days longer hospitalizations compared to patients without acute kidney injury (95% confidence interval, 4.4-6.7). Acute kidney injury in acute-COVID-19 and MIS-C may be related to inflammation and/or dehydration. Further research in larger pediatric cohorts is needed to better characterize risk factors for acute kidney injury in acute-COVID-19 and with MIS-C consequent to COVID-19.