Association of Fibroblast Growth Factor 23 with Blood Pressure in Primary Proteinuric Glomerulopathies.

INTRODUCTION: Fibroblast growth factor 23 (FGF23) has direct effects on the vasculature and myocardium, and high levels of FGF23 are a risk factor for cardiovascular disease (CVD); however, the impact of FGF23 on CVD in primary proteinuric glomerulopathies has not been addressed. METHODS: The associations of baseline plasma intact FGF23 levels with resting blood pressure (BP) and lipids over time among adults and children with proteinuric glomerulopathies enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were analyzed using generalized estimating equation regression analyses. Models were adjusted for age, sex, glomerular diagnosis, follow-up time, estimated glomerular filtration rate, urine protein/creatinine ratio, obesity, and serum phosphorous levels. RESULTS: Two hundred and four adults with median FGF23 77.5 (IQR 51.3-119.3) pg/mL and 93 children with median FGF23 62.3 (IQR 44.6-83.6) pg/mL were followed for a median of 42 (IQR 20.5-54) months. In adjusted models, each 1 µg/mL increase in FGF23 was associated with a 0.3 increase in systolic BP index at follow-up (p < 0.001). Greater baseline FGF23 was associated with greater odds of hypertensive BP (OR = 1.0003; 95% CI 1.001-1.006, p = 0.03) over time. Compared to tertile 1, tertile 2 (OR = 2.1; 95% CI 1.12-3.99, p = 0.02), and tertile 3 (OR = 3; 95% CI 1.08-8.08, p = 0.04), FGF23 levels were associated with greater odds of hypertensive BP over time. Tertile 2 was associated with greater triglycerides compared to tertile 1 (OR = 48.1; 95% CI 4.4-91.9, p = 0.03). CONCLUSION: Overall, higher baseline FGF23 was significantly associated with hypertensive BP over time in individuals with proteinuric glomerulopathies. Further study of FGF23 as a therapeutic target for reducing CVD in proteinuric glomerular disease is warranted.

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.

Estrogen Signaling Influences Nephron Segmentation of the Zebrafish Embryonic Kidney.

Despite significant advances in understanding nephron segment patterning, many questions remain about the underlying genes and signaling pathways that orchestrate renal progenitor cell fate choices and regulate differentiation. In an effort to identify elusive regulators of nephron segmentation, our lab conducted a high-throughput drug screen using a bioactive chemical library and developing zebrafish, which are a conserved vertebrate model and particularly conducive to large-scale screening approaches. 17ß-estradiol (E2), which is the dominant form of estrogen in vertebrates, was a particularly interesting hit from this screen. E2 has been extensively studied in the context of gonad development, but roles for E2 in nephron development were unknown. Here, we report that exogenous estrogen treatments affect distal tubule composition, namely, causing an increase in the distal early segment and a decrease in the neighboring distal late. These changes were noted early in development but were not due to changes in cell dynamics. Interestingly, exposure to the xenoestrogens ethinylestradiol and genistein yielded the same changes in distal segments. Further, upon treatment with an estrogen receptor 2 (Esr2) antagonist, PHTPP, we observed the opposite phenotypes. Similarly, genetic deficiency of the Esr2 analog, esr2b, revealed phenotypes consistent with that of PHTPP treatment. Inhibition of E2 signaling also resulted in decreased expression of essential distal transcription factors, irx3b and its target irx1a. These data suggest that estrogenic compounds are essential for distal segment fate during nephrogenesis in the zebrafish pronephros and expand our fundamental understanding of hormone function during kidney organogenesis.

Isolated nocturnal hypertension in pediatric kidney transplant recipients.

BACKGROUND: Isolated nocturnal hypertension (INH) is defined as nighttime hypertension in the setting of normal daytime blood pressure (BP), diagnosed by ambulatory BP monitoring (ABPM). METHODS AND RESULTS: Hypertension affects 60%-80% of pediatric kidney transplant recipients, and INH is the most common type of ambulatory hypertension. INH is associated with an increased prevalence of hypertension-mediated target organ damage such as left ventricular hypertrophy in adults and in pediatric kidney transplant recipients. CONCLUSION: Ambulatory BP monitoring should be performed annually in all pediatric kidney transplant recipients to diagnose hypertension phenotypes that are not detectable by office BP such as masked hypertension, white-coat hypertension, or INH. Isolated nocturnal hypertension in pediatric transplant patients requires study as a treatment target.