Nephron number and its determinants: a 2020 update

Charlton, Jennifer R.; Baldelomar, Edwin J.; Hyatt, Dylan M.; Bennett, Kevin M.

doi:10.1007/s00467-020-04534-2

Cited by 27 publications

(17 citation statements)

References 82 publications

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“…Most translational AKI models do not account for the additional complexity of pediatric AKI including the concept of development as a biologic variable (DABV) . The association between premature birth and kidney function and maturation remain incompletely understood . Furthermore, the associations between a single AKI episode during kidney development and short-term and long-term outcomes remain unclear .…”

Section: Methodsmentioning

confidence: 99%

“…102 The association between premature birth and kidney function and maturation remain incompletely understood. 103 Furthermore, the associations between a single AKI episode during kidney development and short-term and long-term outcomes remain unclear. 104 Potential sex differences in AKI have prevented the inclusion of both males and females together in preclinical animal studies.…”

Section: Consensus Statement 5b (Recommendation)mentioning

confidence: 99%

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Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children

et al. 2022

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ImportanceIncreasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge.ObjectiveTo develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy.Evidence ReviewAt the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations.FindingsThe meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy.Conclusions and RelevanceExisting evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

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Section: Methodsmentioning

confidence: 99%

Section: Consensus Statement 5b (Recommendation)mentioning

confidence: 99%

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children

et al. 2022

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“…The number of nephrons is determined by congenital genetic factors and an acquired intrauterine developmental environment ( Charlton et al, 2021 ). In normal kidney development, metanephric mesenchymal cell (MMC) is the precursor of the glomerulus, and its maintenance including preventing apoptosis, cell proliferation, and trans-differentiation is the key determinants of nephron endowment ( O'Brien, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Protective role of endorepellin in renal developmental programming

Tang

Sun²,

Shen³

et al. 2022

Front. Cell Dev. Biol.

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Adverse intrauterine and early postnatal environment cause reduced nephron endowment and subsequent hypertension, chronic kidney disease (CKD). Exploring modifiable approaches is particularly important to alleviate the global burden of CKD. Enhanced glomerular progenitor cell apoptosis is a major contributor to renal developmental programming. The differentially expressed protein perlecan, which we previously identified using proteomics, is an important extracellular matrix glycoprotein, and its domain V (endorepellin) can inhibit apoptosis through a paracrine form. In explanted mice embryonic metanephros, we found that endorepellin can rescue glomeruli-deficit phenotype resulting from malnutrition, and this protective effect was also verified in vivo using a renal developmental programming model which was given a low-protein diet during pregnancy. We further demonstrated that endorepellin significantly inhibited glomerular progenitor cell apoptosis which activates ERK1/2 phosphorylation. Our results show that endorepellin rescues the nephron number reduction in renal developmental programming, possibly through the inhibition of progenitor cell apoptosis via the ERK1/2 pathway.

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“…Also, in the current setting we were not able to perform the experiment using cationic ferritin enhanced-MRI, a novel and promising tool to quantify perfused glomeruli. This method, however, would not provide insight into differences in the developmental stages of the glomeruli that were found [ 30 , 31 ]. Secondarily, kidneys were embedded in paraffin: a method known to cause 40–50% shrinkage of soft tissues such as the kidney [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Glomerular developmental delay and proteinuria in the preterm neonatal rabbit

et al. 2020

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Recent advances in neonatal care have improved the survival rate of those born premature. But prenatal conditions, premature birth and clinical interventions can lead to transient and permanent problems in these fragile patients. Premature birth (<36 gestational weeks) occurs during critical renal development and maturation. Some consequences have been observed but the exact pathophysiology is still not entirely known. This experimental animal study aims to investigate the effect of premature birth on postnatal nephrogenesis in premature neonatal rabbits compared to term rabbits of the same corrected age. We analyzed renal morphology, glomerular maturity and functional parameters (proteinuria and protein/creatinine ratio) in three cohorts of rabbit pups: preterm (G28), preterm at day 7 of life (G28+7) and term at day 4 of life (G31+4). We found no significant differences in kidney volume and weight, and relative kidney volume between the cohorts. Nephrogenic zone width increased significantly over time when comparing G31 + 4 to G28. The renal corpuscle surface area, in the inner cortex and outer cortex, tended to decrease significantly after birth in both preterm and term groups. With regard to glomerular maturity, we found that the kidneys in the preterm cohorts were still in an immature state (presence of vesicles and capillary loop stage). Importantly, significant differences in proteinuria and protein/creatinine ratio were found. G28 + 7 showed increased proteinuria (p = 0.019) and an increased protein/creatinine ratio (p = 0.023) in comparison to G31 +4. In conclusion, these results suggest that the preterm rabbit kidney tends to linger in the immature glomerular stages and shows signs of a reduced renal functionality compared to the kidney born at term, which could in time lead to short- and long-term health consequences.

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Nephron number and its determinants: a 2020 update

Cited by 27 publications

References 82 publications

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children

Protective role of endorepellin in renal developmental programming

Glomerular developmental delay and proteinuria in the preterm neonatal rabbit

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