Immature megalin expression in the preterm neonatal kidney is associated with urinary loss of vitamin carrier proteins

Charlton, Jennifer R.; Harer, Matthew W.; Swan, Courtney C; Nielsen, Rikke

doi:10.1038/s41390-018-0261-z

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…Developmental changes enhance complexity to the perturbed pharmacokinetics in critical illness [ 19 ]. Across the continuum of pediatric patients, body composition, organ size, organ function, and gene expression vary, leading to alterations in cellular function and metabolic activity.…”

Section: Resultsmentioning

confidence: 99%

“…During this transition, the risk of nephrotoxicity may be increased, particularly with substances eliminated by the kidney [ 23 ]. In neonates, the immaturity of the tubules in early life may play a role in the mechanism for nephrotoxins with injury that increases with increasing intracellular concentration (e.g., aminoglycosides) [ 19 ]. Concurrently, a neonate’s inability to maximally concentrate their urine may predispose to intravascular volume depletion which increases the nephrotoxic potential of medications impacting kidney hemodynamics [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

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Advances in pediatric acute kidney injury pharmacology and nutrition: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference

Wong Vega,

Starr,

Brophy

et al. 2023

Pediatr Nephrol

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Background In the past decade, there have been substantial advances in our understanding of pediatric AKI. Despite this progress, large gaps remain in our understanding of pharmacology and nutritional therapy in pediatric AKI. Methods During the 26th Acute Disease Quality Initiative (ADQI) Consensus Conference, a multidisciplinary group of experts reviewed the evidence and used a modified Delphi process to achieve consensus on recommendations for gaps and advances in care for pharmacologic and nutritional management of pediatric AKI. The current evidence as well as gaps and opportunities were discussed, and recommendations were summarized. Results Two consensus statements were developed. (1) High-value, kidney-eliminated medications should be selected for a detailed characterization of their pharmacokinetics, pharmacodynamics, and pharmaco-“omics” in sick children across the developmental continuum. This will allow for the optimization of real-time modeling with the goal of improving patient care. Nephrotoxin stewardship will be identified as an organizational priority and supported with necessary resources and infrastructure. (2) Patient-centered outcomes (functional status, quality of life, and optimal growth and development) must drive targeted nutritional interventions to optimize short- and long-term nutrition. Measures of acute and chronic changes of anthropometrics, body composition, physical function, and metabolic control should be incorporated into nutritional assessments. Conclusions Neonates and children have unique metabolic and growth parameters compared to adult patients. Strategic investments in multidisciplinary translational research efforts are required to fill the knowledge gaps in nutritional requirements and pharmacological best practices for children with or at risk for AKI.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Advances in pediatric acute kidney injury pharmacology and nutrition: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference

Wong Vega,

Starr,

Brophy

et al. 2023

Pediatr Nephrol

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“…Low 25OHD levels in the maternal and cord blood have been found to be significantly associated with decreased birth weight of infants [5]. Vitamin D deficiency is common in preterm infants [6] and vitamin D supplementation in women at high risk of vitamin D deficiency leads to improved neonatal handling of Ca [2]. Many studies have shown that maternal vitamin D level might affect fetal growth.…”

Section: Introductionmentioning

confidence: 99%

Maternal Vitamin D in the Late First and Second Trimester is Beneficial for Healthy Development of Fetal Head Circumference

Hasegawa¹,

Manabe²,

Izumi³

et al. 2020

Int J Nurs Clin Pract

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“…Additionally, PT dysfunction can prevent normal uptake of filtered vitamin carrier proteins that bind to megalin and cubilin, including vitamin D-binding protein (DBP) and retinol-binding protein (RBP) (10,42). Failure to reclaim these carrier proteins can lead to vitamin deficiencies (5,38). This is particularly true for vitamin D, as the PT is the primary site for vitamin D reclamation and activation (11).…”

Section: Introductionmentioning

confidence: 99%

Hemoglobin alters vitamin carrier uptake and vitamin D metabolism in proximal tubule cells: implications for sickle cell disease

Gliozzi

Rbaibi

Long

et al. 2019

American Journal of Physiology-Cell Physiology

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Kidney disease, including proximal tubule (PT) dysfunction, and vitamin D deficiency are among the most prevalent complications in sickle cell disease (SCD) patients. Although these two comorbidities have never been linked in SCD, the PT is the primary site for activation of vitamin D. Precursor 25-hydroxyvitamin D [25(OH)D] bound to vitamin D-binding protein (DBP) is taken up by PT cells via megalin/cubilin receptors, hydroxylated to the active 1,25-dihydroxyvitamin D [1,25(OH)2D] form, and released into the bloodstream. We tested the hypothesis that cell-free hemoglobin (Hb) filtered into the PT lumen impairs vitamin D uptake and metabolism. Hb at concentrations expected to be chronically present in the ultrafiltrate of SCD patients competed directly with DBP for apical uptake by PT cells. By contrast, uptake of retinol binding protein was impaired only at considerably higher Hb concentrations. Prolonged exposure to Hb led to increased oxidative stress in PT cells and to a selective increase in mRNA levels of the CYP27B1 hydroxylase, although protein levels were unchanged. Hb exposure also impaired vitamin D metabolism in PT cells, resulting in reduced ratio of 1,25(OH)2D:25(OH)D. Moreover, plasma levels of 1,25(OH)2D were reduced in a mouse model of SCD. Together, our data suggest that Hb released by chronic hemolysis has multiple effects on PT function that contribute to vitamin D deficiency in SCD patients.

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Immature megalin expression in the preterm neonatal kidney is associated with urinary loss of vitamin carrier proteins

Cited by 6 publications

References 36 publications

Advances in pediatric acute kidney injury pharmacology and nutrition: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference

Advances in pediatric acute kidney injury pharmacology and nutrition: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference

Maternal Vitamin D in the Late First and Second Trimester is Beneficial for Healthy Development of Fetal Head Circumference

Hemoglobin alters vitamin carrier uptake and vitamin D metabolism in proximal tubule cells: implications for sickle cell disease

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