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http://onlinelibrary.wiley.com/doi/10.1111/joa.12239/abstract;jsessionid=B63AAD445BB49952BDFFD1407ADD0B85.f03t04
http://onlinelibrary.wiley.com/doi/10.1111/joa.12239/abstract;jsessionid=B63AAD445BB49952BDFFD1407ADD0B85.f03t04
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© 2014 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.
© 2014 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

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Cite this page: Hill, M.A. (2024, March 29) Embryology Renal System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Renal_System_Development

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Renal System Development

<pubmed limit=5>Renal System Development</pubmed>

2015

The yin and yang of kidney development and Wilms' tumors

Genes Dev. 2015 Mar 1;29(5):467-82. doi: 10.1101/gad.256396.114.

Hohenstein P1, Pritchard-Jones K2, Charlton J2.

Abstract

Wilms' tumor, or nephroblastoma, is the most common pediatric renal cancer. The tumors morphologically resemble embryonic kidneys with a disrupted architecture and are associated with undifferentiated metanephric precursors. Here, we discuss genetic and epigenetic findings in Wilms' tumor in the context of renal development. Many of the genes implicated in Wilms' tumorigenesis are involved in the control of nephron progenitors or the microRNA (miRNA) processing pathway. Whereas the first group of genes has been extensively studied in normal development, the second finding suggests important roles for miRNAs in general-and specific miRNAs in particular-in normal kidney development that still await further analysis. The recent identification of Wilms' tumor cancer stem cells could provide a framework to integrate these pathways and translate them into new or improved therapeutic interventions. © 2015 Hohenstein et al.; Published by Cold Spring Harbor Laboratory Press. KEYWORDS: Wilms’ tumor; Wt1; kidney development; miRNA; nephron progenitor cells; β-catenin

PMID 25737276

http://genesdev.cshlp.org/content/29/5/467

© 2015 Hohenstein et al.; Published by Cold Spring Harbor Laboratory Press This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

Histone deacetylase 1 and 2 regulate Wnt and p53 pathways in the ureteric bud epithelium

Development. 2015 Mar 15;142(6):1180-92. doi: 10.1242/dev.113506.

Chen S1, Yao X1, Li Y1, Saifudeen Z1, Bachvarov D2, El-Dahr SS3.

Abstract

Histone deacetylases (HDACs) regulate a broad range of biological processes through removal of acetyl groups from histones as well as non-histone proteins. Our previous studies showed that Hdac1 and Hdac2 are bound to promoters of key renal developmental regulators and that HDAC activity is required for embryonic kidney gene expression. However, the existence of many HDAC isoforms in embryonic kidneys raises questions concerning the possible specificity or redundancy of their functions. We report here that targeted deletion of both the Hdac1 and Hdac2 genes from the ureteric bud (UB) cell lineage of mice causes bilateral renal hypodysplasia. One copy of either Hdac1 or Hdac2 is sufficient to sustain normal renal development. In addition to defective cell proliferation and survival, genome-wide transcriptional profiling revealed that the canonical Wnt signaling pathway is specifically impaired in UB(Hdac1,2-/-) kidneys. Our results also demonstrate that loss of Hdac1 and Hdac2 in the UB epithelium leads to marked hyperacetylation of the tumor suppressor protein p53 on lysine 370, 379 and 383; these post-translational modifications are known to boost p53 stability and transcriptional activity. Genetic deletion of p53 partially rescues the development of UB(Hdac1,2-/-) kidneys. Together, these data indicate that Hdac1 and Hdac2 are crucial for kidney development. They perform redundant, yet essential, cell lineage-autonomous functions via p53-dependent and -independent pathways. © 2015. Published by The Company of Biologists Ltd. KEYWORDS: Branching morphogenesis; Histone; Kidney; Mouse; Ureteric bud; Wnt; p53 (Trp53)

PMID 25758227


Node retraction during patterning of the urinary collecting duct system

J Anat. 2015 Jan;226(1):13-21. doi: 10.1111/joa.12239. Epub 2014 Oct 8.

Lindström NO1, Chang CH, Valerius MT, Hohenstein P, Davies JA.

Abstract

This report presents a novel mechanism for remodelling a branched epithelial tree. The mouse renal collecting duct develops by growth and repeated branching of an initially unbranched ureteric bud: this mechanism initially produces an almost fractal form with young branches connected to the centre of the kidney via a sequence of nodes (branch points) distributed widely throughout the developing organ. The collecting ducts of a mature kidney have a different form: from the nephrons in the renal cortex, long, straight lengths of collecting duct run almost parallel to one another through the renal medulla, and open together to the renal pelvis. Here we present time-lapse studies of E11.5 kidneys growing in culture: after about 5 days, the collecting duct trees show evidence of 'node retraction', in which the node of a 'Y'-shaped branch moves downwards, shortening the stalk of the 'Y', lengthening its arms and narrowing their divergence angle so that the 'Y' becomes a 'V'. Computer simulation suggests that node retraction can transform a spread tree, like that of an early kidney, into one with long, almost-parallel medullary rays similar to those seen in a mature real kidney. © 2014 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society. KEYWORDS: branching morphogenesis; collecting duct; development; embryonic kidney; modelling; organogenesis; pattern formation; ureteric bud

PMID 25292187

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299504/

http://onlinelibrary.wiley.com/doi/10.1111/joa.12239/abstract;jsessionid=B63AAD445BB49952BDFFD1407ADD0B85.f03t04

Videos - http://onlinelibrary.wiley.com/doi/10.1111/joa.12239/suppinfo

© 2014 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

2014

Non-canonical Wnt5a/Ror2 signaling regulates kidney morphogenesis by controlling intermediate mesoderm extension

Hum Mol Genet. 2014 Jul 31. pii: ddu397. [Epub ahead of print]

Yun K1, Ajima R1, Sharma N1, Costantini F2, Mackem S1, Lewandoski M1, Yamaguchi TP1, Perantoni AO3.

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) affect about 1 in 500 births and are a major cause of morbidity in infants. Duplex collecting systems rank among the most common abnormalities of CAKUT, but the molecular basis for this defect is poorly understood. In mice, conditional deletion of Wnt5a in mesoderm results in bilateral duplex kidney and ureter formation. The ureteric buds (UB) in mutants emerge as doublets from the intermediate mesoderm (IM)-derived nephric duct (ND) without anterior expansion of the Gdnf expression domain in the surrounding mesenchyme. Wnt5a is normally expressed in a graded manner at the posterior end of the IM, but its expression is down regulated prior to UB outgrowth at E10.5. Furthermore, ablation of Wnt5a in mesoderm with an inducible Cre at E7.5 results in duplex UBs; whereas, ablation at E8.5 yields normal UB outgrowth, demonstrating that Wnt5a functions in IM development well before formation of the metanephros. In mutants, the posterior ND is duplicated and surrounding Pax2-positive mesenchymal cells persist in the nephric cord, suggesting that disruption of normal ND patterning prompts the formation of duplex ureters and kidneys. Ror2 homozygous mutants, which infrequently yield duplex collecting systems, show a dramatic increase in incidence with the additional deletion of one copy of Wnt5a, implicating this receptor in non-canonical Wnt5a signaling during IM development. This work provides the first evidence of a role for Wnt5a/Ror2 signaling in IM extension and offers new insight into the etiology of CAKUT and possible involvement of Wnt5a/Ror2 mutations. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

PMID 25082826


Renal branching morphogenesis: Morphogenetic and signaling mechanisms

Semin Cell Dev Biol. 2014 Jul 28. pii: S1084-9521(14)00222-5. doi: 10.1016/j.semcdb.2014.07.011. [Epub ahead of print] Blake J1, Rosenblum ND2.

Abstract

The human kidney is composed of an arborized network of collecting ducts, calyces and urinary pelvis that facilitate urine excretion and regulate urine composition. The renal collecting system is formed in utero, completed by the 34th week of gestation in humans, and dictates final nephron complement. The renal collecting system arises from the ureteric bud, a derivative of the intermediate-mesoderm derived nephric duct that responds to inductive signals from adjacent tissues via a process termed ureteric induction. The ureteric bud subsequently undergoes a series of iterative branching and remodeling events in a process called renal branching morphogenesis. Altered signaling that disrupts patterning of the nephric duct, ureteric induction, or renal branching morphogenesis leads to varied malformations of the renal collecting system collectively known as congenital anomalies of the kidney and urinary tract (CAKUT) and is the most frequently detected congenital renal aberration in infants. Here, we describe critical morphogenetic and cellular events that govern nephric duct specification, ureteric bud induction, renal branching morphogenesis, and cessation of renal branching morphogenesis. We also highlight salient molecular signaling pathways that govern these processes, and the investigative techniques used to interrogate them. Copyright © 2014. Published by Elsevier Ltd. KEYWORDS: Branching morphogenesis; CAKUT; Kidney; Signaling; Ureteric bud

PMID 25080023


Renal development: a complex process dependent on inductive interaction

Curr Pediatr Rev. 2014;10(2):107-14.

Upadhyay KK, Silverstein DM1.

Abstract

Renal development begins in-utero and continues throughout childhood. Almost one-third of all developmental anomalies include structural or functional abnormalities of the urinary tract. There are three main phases of in-utero renal development: Pronephros, Mesonephros and Metanephros. Within three weeks of gestation, paired pronephri appear. A series of tubules called nephrotomes fuse with the pronephric duct. The pronephros elongates and induces the nearby mesoderm, forming the mesonephric (Woffian) duct. The metanephros is the precursor of the mature kidney that originates from the ureteric bud and the metanephric mesoderm (blastema) by 5 weeks of gestation. The interaction between these two components is a reciprocal process, resulting in the formation of a mature kidney. The ureteric bud forms the major and minor calyces, and the collecting tubules while the metanephrogenic blastema develops into the renal tubules and glomeruli. In humans, all of the nephrons are formed by 32 to 36 weeks of gestation. Simultaneously, the lower urinary tract develops from the vesico urethral canal, ureteric bud and mesonephric duct. In utero, ureters deliver urine from the kidney to the bladder, thereby creating amniotic fluid. Transcription factors, extracellular matrix glycoproteins, signaling molecules and receptors are the key players in normal renal development. Many medications (e.g., aminoglycosides, cyclooxygenase inhibitors, substances that affect the renin-angiotensin aldosterone system) also impact renal development by altering the expression of growth factors, matrix regulators or receptors. Thus, tight regulation and coordinated processes are crucial for normal renal development.

PMID 25088264


2012

Glomerulogenesis: Can it predict the gestational age? A study of 176 fetuses

Indian J Pathol Microbiol. 2012 Jul;55(3):303-7. doi: 10.4103/0377-4929.101734.

Chikkannaiah P, Roy M, Kangle R, Patil PV. Source Department of Pathology, KLE University's Jawaharlal Nehru Medical College, Belgaum, Karnataka, India.

Abstract

Background: Accurate assessment of gestational age of fetuses is essential from both clinical and medico-legal point of view. Crown-rump length, crown-heel length, foot length, and the weight of the fetus are the commonly used parameters for fetal age assessment. However, this estimate often lacks accuracy and sometimes is necessary to combine other data. An analysis of the embryological development of nephrons in the kidney can assist in this determination. Objective : To correlate the gestational age with the histological study of sequential development of nephrons in fetal kidney. Materials and Methods: This study included 176 fetuses delivered between June 2009 and June 2011 and aged from 12 to 40 weeks. The number of glomerular generations counted in hematoxylin and eosin-stained microscopic sections of the kidneys were correlated with the reported period of gestation based on obstetrical methods. Regression analysis was used to determine the statistical significance of the correlation. Results: A high degree of statistically significant correlation was observed between the period of gestation and the number of glomerular generations (P value < 0.0001). Conclusion: The histological assessment of the number of glomerular generations in kidney can be used as a reliable method of estimating fetal age.

PMID 23032821

http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2012;volume=55;issue=3;spage=303;epage=307;aulast=Chikkannaiah

http://www.ijpmonline.org/viewimage.asp?img=IndianJPatholMicrobiol_2012_55_3_303_101734_f4.jpg

Pathway in Kidney Development: Implications for Nephrogenesis

Citation: Saifudeen Z, Liu J, Dipp S, Yao X, Li Y, et al. (2012) A p53-Pax2 Pathway in Kidney Development: Implications for Nephrogenesis. PLoS ONE 7(9): e44869. doi:10.1371/journal.pone.0044869


Copyright: © 2012 Saifudeen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0044869

Bmp7 functions via a polarity mechanism to promote cloacal septation

PLoS One. 2012;7(1):e29372. Epub 2012 Jan 13.

Xu K, Wu X, Shapiro E, Huang H, Zhang L, Hickling D, Deng Y, Lee P, Li J, Lepor H, Grishina I. Source Department of Urology, School of Medicine, New York University, New York, New York, United States of America.

Abstract

BACKGROUND: During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We previously detected Bone morphogenetic protein 7 (Bmp7) expression in the urorectal mesenchyme (URM), and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK) pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse. CONCLUSION/SIGNIFICANCE: Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations.

PMID 22253716

Expression of Bcl-2 and Bax in Mouse Renal Tubules during Kidney Development

PLoS One. 2012;7(2):e32771. Epub 2012 Feb 28.

Song XF, Ren H, Andreasen A, Thomsen JS, Zhai XY. Source Department of Histology and Embryology, Institute of Pathology and Pathophysiology, China Medical University, Shen Yang, Liao Ning, China.

Abstract

Bcl-2 and Bax play an important role in apoptosis regulation, as well as in cell adhesion and migration during kidney morphogenesis, which is structurally and functionally related to mitochondria. In order to elucidate the role of Bcl-2 and Bax during kidney development, it is essential to establish the exact location of their expression in the kidney. The present study localized their expression during kidney development. Kidneys from embryonic (E) 16-, 17-, 18-day-old mouse fetuses, and postnatal (P) 1-, 3-, 5-, 7-, 14-, 21-day-old pups were embedded in Epon. Semi-thin serial sections from two E17 kidneys underwent computer assisted 3D tubule tracing. The tracing was combined with a newly developed immunohistochemical technique, which enables immunohistochemistry on glutaraldehyde fixated plastic embedded sections. Thereby, the microstructure could be described in detail, and the immunochemistry can be performed using exactly the same sections. The study showed that Bcl-2 and Bax were strongly expressed in mature proximal convoluted tubules at all time points, less strongly expressed in proximal straight tubules, and only weakly in immature proximal tubules and distal tubules. No expression was detected in ureteric bud and other earlier developing structures, such as comma bodies, S shaped bodies, glomeruli, etc. Tubules expressing Bcl-2 only were occasionally observed. The present study showed that, during kidney development, Bcl-2 and Bax are expressed differently in the proximal and distal tubules, although these two tubule segments are almost equally equipped with mitochondria. The functional significance of the different expression of Bcl-2 and Bax in proximal and distal tubules is unknown. However, the findings of the present study suggest that the mitochondrial function differs between mature proximal tubules and in the rest of the tubules. The function of Bcl-2 and Bax during tubulogenesis still needs to be investigated.

PMID 22389723 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032771

2010

Kidney development: two tales of tubulogenesis

Curr Top Dev Biol. 2010;90:193-229.

Little M, Georgas K, Pennisi D, Wilkinson L. Source Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Australia.

Abstract

The mammalian kidney may well be one of the most complex organs of postnatal life. Each adult human kidney contains on average more than one million functional filtration units, the nephrons, residing within a specialized cellular interstitium. Each kidney also contains over 25 distinct cell types, each of which must be specifically aligned with respect to each other to ensure both normal development and ultimately, normal renal function. Despite this complexity, the development of the kidney can be simplistically described as the coordinate formation of two distinct sets of tubules. These tubules develop cooperatively with each other in time and space, yet represent two distinct but classical types of tubulogenesis. The first of these tubules, the ureteric bud, forms as an outgrowth of another epithelial tube, the nephric duct, and undergoes extensive branching morphogenesis to create the collecting system of the kidney. The second tubules are the nephrons themselves which arise via a mesenchyme-to-epithelial transition induced by the first set of tubules. These tubules never branch, but must elongate to become intricately patterned and functionally segmented tubules. The molecular drivers for these two tales of tubulogenesis include many gene families regulating tubulogenesis and branching morphogenesis in other organs; however, the individual players and codependent interrelationships between a branched and non-branched tubular network make organogenesis in the kidney unique. Here we review both what is known and remains to be understood in kidney tubulogenesis.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID: 20691850 http://www.ncbi.nlm.nih.gov/pubmed/20691850

Kidney development in the absence of Gdnf and Spry1 requires Fgf10

PLoS Genet. 2010 Jan 15;6(1):e1000809.

Michos O, Cebrian C, Hyink D, Grieshammer U, Williams L, D'Agati V, Licht JD, Martin GR, Costantini F.

Department of Genetics and Development, Columbia University, New York, New York, USA.

Abstract GDNF signaling through the Ret receptor tyrosine kinase (RTK) is required for ureteric bud (UB) branching morphogenesis during kidney development in mice and humans. Furthermore, many other mutant genes that cause renal agenesis exert their effects via the GDNF/RET pathway. Therefore, RET signaling is believed to play a central role in renal organogenesis. Here, we re-examine the extent to which the functions of Gdnf and Ret are unique, by seeking conditions in which a kidney can develop in their absence. We find that in the absence of the negative regulator Spry1, Gdnf, and Ret are no longer required for extensive kidney development. Gdnf-/-;Spry1-/- or Ret-/-;Spry1-/- double mutants develop large kidneys with normal ureters, highly branched collecting ducts, extensive nephrogenesis, and normal histoarchitecture. However, despite extensive branching, the UB displays alterations in branch spacing, angle, and frequency. UB branching in the absence of Gdnf and Spry1 requires Fgf10 (which normally plays a minor role), as removal of even one copy of Fgf10 in Gdnf-/-;Spry1-/- mutants causes a complete failure of ureter and kidney development. In contrast to Gdnf or Ret mutations, renal agenesis caused by concomitant lack of the transcription factors ETV4 and ETV5 is not rescued by removing Spry1, consistent with their role downstream of both RET and FGFRs. This shows that, for many aspects of renal development, the balance between positive signaling by RTKs and negative regulation of this signaling by SPRY1 is more critical than the specific role of GDNF. Other signals, including FGF10, can perform many of the functions of GDNF, when SPRY1 is absent. But GDNF/RET signaling has an apparently unique function in determining normal branching pattern. In contrast to GDNF or FGF10, Etv4 and Etv5 represent a critical node in the RTK signaling network that cannot by bypassed by reducing the negative regulation of upstream signals.

PMID 20084103

Hs2st mediated kidney mesenchyme induction regulates early ureteric bud branching

Dev Biol. 2010 Mar 15;339(2):354-65. Epub 2010 Jan 6.

Shah MM, Sakurai H, Sweeney DE, Gallegos TF, Bush KT, Esko JD, Nigam SK.

Department of Medicine, University of California, San Diego, CA 92093-0693, USA.

Abstract

Heparan sulfate proteoglycans (HSPGs) are central modulators of developmental processes likely through their interaction with growth factors, such as GDNF, members of the FGF and TGFbeta superfamilies, EGF receptor ligands and HGF. Absence of the biosynthetic enzyme, heparan sulfate 2-O-sulfotransferase (Hs2st) leads to kidney agenesis. Using a novel combination of in vivo and in vitro approaches, we have reanalyzed the defect in morphogenesis of the Hs2st(-)(/)(-) kidney. Utilizing assays that separately model distinct stages of kidney branching morphogenesis, we found that the Hs2st(-/-) UB is able to undergo branching and induce mesenchymal-to-epithelial transformation when recombined with control MM, and the isolated Hs2st null UB is able to undergo branching morphogenesis in the presence of exogenous soluble pro-branching growth factors when embedded in an extracellular matrix, indicating that the UB is intrinsically competent. This is in contrast to the prevailing view that the defect underlying the renal agenesis phenotype is due to a primary role for 2-O sulfated HS in UB branching. Unexpectedly, the mutant MM was also fully capable of being induced in recombination experiments with wild-type tissue. Thus, both the mutant UB and mutant MM tissue appear competent in and of themselves, but the combination of mutant tissues fails in vivo and, as we show, in organ culture. We hypothesized a 2OS-dependent defect in the mutual inductive process, which could be on either the UB or MM side, since both progenitor tissues express Hs2st. In light of these observations, we specifically examined the role of the HS 2-O sulfation modification on the morphogenetic capacity of the UB and MM individually. We demonstrate that early UB branching morphogenesis is not primarily modulated by factors that depend on the HS 2-O sulfate modification; however, factors that contribute to MM induction are markedly sensitive to the 2-O sulfation modification. These data suggest that key defect in Hs2st null kidneys is the inability of MM to undergo induction either through a failure of mutual induction or a primary failure of MM morphogenesis. This results in normal UB formation but affects either T-shaped UB formation or iterative branching of the T-shaped UB (possibly two separate stages in collecting system development dependent upon HS). We discuss the possibility that a disruption in the interaction between HS and Wnts (e.g. Wnt 9b) may be an important aspect of the observed phenotype. This appears to be the first example of a defect in the MM preventing advancement of early UB branching past the first bifurcation stage, one of the limiting steps in early kidney development.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID 20059993

A novel, low-volume method for organ culture of embryonic kidneys that allows development of cortico-medullary anatomical organization.

Sebinger DD, Unbekandt M, Ganeva VV, Ofenbauer A, Werner C, Davies JA. PLoS One. 2010 May 10;5(5):e10550.

PMID 20479933

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010550

2009

Size and volume charts of fetal kidney, renal pelvis and adrenal gland

Ultrasound Obstet Gynecol. 2012 Dec;40(6):659-64. doi: 10.1002/uog.11169.

van Vuuren SH1, Damen-Elias HA, Stigter RH, van der Doef R, Goldschmeding R, de Jong TP, Westers P, Visser GH, Pistorius LR.

Abstract

OBJECTIVE: To establish reference curves for size and volume of the fetal kidney, renal pelvis and adrenal gland, as measured using ultrasound from the 15(th) week of gestation. METHODS: This was a prospective, longitudinal study of 96 fetuses in low-risk singleton pregnancies, in which we performed serial ultrasound examinations at 4-week intervals. The length and anteroposterior and transverse diameters of both kidneys, the anteroposterior and transverse diameters of the renal pelvises and the length of the adrenal glands were measured three times at each examination, with the average being used for further analysis. Reference charts were constructed using multilevel statistical analysis and comparisons were made with previously published charts derived from cross-sectional data. RESULTS: We present nomograms for fetal kidney dimensions and volume, renal pelvis dimensions and adrenal gland length. The new charts show differences in shape and have narrower percentile bands in comparison to previously published reference ranges. CONCLUSIONS: These new charts of measurements of the fetal kidney, renal pelvis and adrenal gland, from a prospective, longitudinal study, may be useful in the diagnosis and assessment of pathology of the kidney and adrenal gland. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

PMID 22581671

http://onlinelibrary.wiley.com/store/10.1002/uog.11169/asset/uog11169.pdf?v=1&t=hvnerdbc&s=b7336fa0c441ea054a4fa7a13b64a50f2bd93c29


Good graphs of US renal growth.

The kidney from prenatal to adult life: perinatal programming and reduction of number of nephrons during development

Am J Nephrol. 2009;30(2):162-70. Epub 2009 Apr 2.

Puddu M, Fanos V, Podda F, Zaffanello M. Source Department of Pediatrics and Clinical Medicine, NICU, University of Cagliari, Cagliari, Italy.

Abstract

Modified embryonic-fetal development resulting in low birth weight may lead to a reduced nephron endowment, hypertension and renal diseases in adulthood. Regarding the involvement of genetic factors, several environmental conditions may also contribute towards reducing the number of nephrons in the fetus and infant, subsequently constituting a health burden in later life. To date no methods of investigation for the early detection of a reduced nephron reserve are available. However, more structured studies should be implemented to investigate the role of angiotensin-converting enzyme inhibitors in managing proteinurias and glomerulosclerosis in children with renal conditions characterized by reduce nephron number and glomerular hypertrophic changes. In view of the current lack of specific methods of investigation and management, close monitoring of children and young adults at risk of reduced renal reserve should be carried out to enhance the early detection of potential changes in renal function.

  • humans the overall number of nephrons ranges be- tween 617,000 and 1,075,000 (mean 850,000 nephrons).
  • hypertensive adults mean of about 702,000 nephrons.
  • normotensive subjects with a mean of 1,429,000 nephrons.

Copyright 2009 S. Karger AG, Basel.

PMID 19339773


Human renal function maturation: a quantitative description using weight and postmenstrual age

Pediatr Nephrol. 2009 Jan;24(1):67-76. Epub 2008 Oct 10.

Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, Chatelut E, Grubb A, Veal GJ, Keir MJ, Holford NH. Source Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden.

Abstract

This study pools published data to describe the increase in glomerular filtration rate (GFR) from very premature neonates to young adults. The data comprises measured GFR (using polyfructose, (51)Cr-EDTA, mannitol or iohexol) from eight studies (n = 923) and involved very premature neonates (22 weeks postmenstrual age) to adulthood (31 years). A nonlinear mixed effects approach (NONMEM) was used to examine the influences of size and maturation on renal function. Size was the primary covariate, and GFR was standardized for a body weight of 70 kg using an allometric power model. Postmenstrual age (PMA) was a better descriptor of maturational changes than postnatal age (PNA). A sigmoid hyperbolic model described the nonlinear relationship between GFR maturation and PMA. Assuming an allometric coefficient of 3/4, the fully mature (adult) GFR is predicted to be 121.2 mL/min per 70 kg [95% confidence interval (CI) 117-125]. Half of the adult value is reached at 47.7 post-menstrual weeks (95%CI 45.1-50.5), with a Hill coefficient of 3.40 (95%CI 3.03-3.80). At 1-year postnatal age, the GFR is predicted to be 90% of the adult GFR. Glomerular filtration rate can be predicted with a consistent relationship from early prematurity to adulthood. We propose that this offers a clinically useful definition of renal function in children and young adults that is independent of the predictable changes associated with age and size.

PMID 18846389

Kidney development: from ureteric bud formation to branching morphogenesis

Curr Opin Genet Dev. 2009 Oct;19(5):484-90. Epub 2009 Oct 14.

Michos O.

Department of Genetics and Development, Columbia University Medical Center, HHSC1416, New York, NY 10032, USA. om2142@columbia.edu

Abstract Epithelial branching morphogenesis is critical to the formation of various organs such as the vasculature, mammary glands, lungs, and kidneys in vertebrate embryos. One fascinating aspect of branching morphogenesis is to understand how a simple epithelial tube grows by reiterative branching to form a complex epithelial tree structure. Recent studies combining mouse genetics and chimeric analysis with live imaging have uncovered the molecular networks and interactions that govern kidney branching morphogenesis. This review focuses on ureteric bud (UB) formation and epithelial branching during kidney development. The invasion of the metanephric mesenchyme by the UB is a fundamental step toward establishing the cyto-architecture of the kidney and determining the number of nephrons, which form the filtration units of the adult kidney.


PMID 19828308

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783241

--Mark Hill 07:20, 8 April 2011 (EST) Good molecular development overview figures.

Cell and molecular biology of kidney development

Reidy KJ, Rosenblum ND. Semin Nephrol. 2009 Jul;29(4):321-37. Review. PMID: 19615554 http://www.ncbi.nlm.nih.gov/pubmed/19615554

Semin Nephrol. 2009 Jul;29(4):321-37. Cell and molecular biology of kidney development. Reidy KJ, Rosenblum ND.

Department of Pediatrics/Division of Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, 3415 Bainbridge Ave, Bronx, NY 10467, USA. Abstract Abnormalities of kidney and urinary tract development are the most common cause of end-stage kidney failure in childhood in the United States. Over the past 20 years, the advent of mutant and transgenic mice and the manipulation of gene expression in other animal models has resulted in major advances in identification of the cellular and molecular mechanisms that direct kidney morphogenesis, providing insights into the pathophysiology of renal and urologic anomalies. This review focuses on the molecular mechanisms that define kidney progenitor cell populations, induce nephron formation within the metanephric mesenchyme, initiate and organize ureteric bud branching, and participate in terminal differentiation of the nephron. Highlighted are common signaling pathways that function at multiple stages during kidney development, including signaling via Wnts, bone morphogenic proteins, fibroblast growth factor, sonic hedgehog, RET/glial cell-derived neurotrophic factor, and notch pathways. Also emphasized are the roles of transcription factors Odd1, Eya1, Pax2, Lim1, and WT-1 in directing renal development. Areas requiring future investigation include the factors that modulate signaling pathways to provide temporal and site-specific effects. The evolution of our understanding of the cellular and molecular mechanisms of kidney development may provide methods for improved diagnosis of renal anomalies and, hopefully, targets for intervention for this common cause of childhood end-stage kidney disease.

PMID 19615554

How does the ureteric bud branch?

J Am Soc Nephrol. 2009 Jul;20(7):1465-9. Epub 2008 Dec 3.

Nigam SK, Shah MM.

Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, USA. snigam@ucsd.edu Abstract Many genes that modulate kidney development have been identified; however, the molecular interactions that direct arborization of the ureteric bud (UB) remain incompletely understood. This article discusses how "systems" approaches may shed light on the structure of the gene network during UB branching morphogenesis and the mechanisms involved in the formation of a branched collecting system from a straight epithelial tube in the context of a stage model. In vitro and genetic studies suggest that the stages seem to be governed by a conserved network of genes that establish a "tip-stalk generator"; these genes sustain iterative UB branching tubulogenesis through minimal alterations in the network architecture as a budding system shifts to one that autocatalytically branches through budding. The differential expression of stage-specific positive and inhibitory factors in the mesenchyme, likely presented in the context of heparan sulfate proteoglycans, and effector molecules in the epithelium seems to regulate advancement between stages; similar principles may apply to other branching epithelia such as the lung, salivary gland, pancreas, mammary gland, and prostate. Active mesenchymal interactions with the UB seem to govern vectorial arborization and tapering of the collecting system and its terminal differentiation. Cessation of branching correlates with induction of mesenchyme as well as local extracellular matrix changes. Perturbations of these mechanisms and/or single-nucleotide polymorphisms in genes regulating UB branching may predispose to a variety of renal diseases (e.g., hypertension and chronic kidney disease) by altering nephron number. Decentralization of the gene-protein interaction network may explain the relative paucity of branching phenotypes in mutant mice and in human disease.

PMID 19056872

2007

The spectrum of podocytopathies: a unifying view of glomerular diseases

Kidney Int. 2007 Jun;71(12):1205-14. Epub 2007 Apr 4.

Wiggins RC. Source Nephrology Division, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0676, USA. rwiggins@umich.edu

Abstract

Glomerular diseases encompass a broad array of clinicopathologically defined syndromes which together account for 90% of end-stage kidney disease costing $20 billion per annum to treat in the United States alone. Recent insights have defined the central role of the podocyte as both the regulator of glomerular development as well as the determinant of progression to glomerulosclerosis. We can now place all glomerular diseases within this spectrum of podocytopathies with predictable outcomes based on podocyte biology impacted by temporal, genetic, and environmental cues. This simplified construct is particularly useful to rationalize clinical effort toward podocyte preservation and prevention of progression as well as to focus basic research effort on understanding podocyte biology and for clinical research toward development of practical monitoring strategies for podocyte injury, dysfunction, and loss.

PMID 17410103


2005

Quantitative analysis of the nephron during human fetal kidney development

Vojnosanit Pregl. 2005 Apr;62(4):281-6.

Daković-Bjelaković M, Vlajković S, Cukuranović R, Antić S, Bjelaković G, Mitić D. Source University of Nis, Medical Faculty, Institute of Anatomy, Clinical Centre, Nis. Abstract BACKGROUND: The development of human kidney is a complex process. The number, shape, size, and distribution of nephrons as functional units in a kidney, provide some important information about the organization of the kidney. The aim of this study was to extend the knowledge of the developing human kidney by studying nephrons in the kidney's cortex during gestation. METHODS: Kidney tissue specimens of 32 human fetuses, the gestational age from IV lunar month (LM IV) to LM X, were analysed. Specimens were divided in ten groups based on gestational age. Stereological methods were used at the light microscopic level to estimate the volume densities of the corpuscular and tubular components of the nephron in the cortex of the developing human kidney. RESULTS: Nephron polymorphism was the main characteristic of the human fetal kidney during development. In younger fetuses, just below the renal capsule, there was a wide nephrogenic zone. It contained the condensed mesenchyme and terminal ends of the ureteric bud. Nephrons, in the different stages of development, were located around the ureteric bud which branched in the cortical nephrogenic zone and induced nephrogenesis. More mature nephrons were located in the deeper part of the cortex, close to the juxta-medullary junction. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Glomeruli changed their size and shape, while the tubules changed their length and convolution. Renal cortex became wider and contained the more mature glomeruli and the more convoluted tubules. The volume density of the tubular component of the nephron increased continually from 10.53% (LM IVa) to 27.7% (LM X). Renal corpuscles changed their volume density irregularly during gestation, increasing from 13% (LM IVa) to 15.5% (LM IVb). During the increase of gestational age, the volume density of corpuscular component of the nephron decreased to 11.7% (LM VIII), then went on increasing until the end of the intrauterine development (LM X) when corpuscles occupied 16.73% of the cortical volume. The volume density of the developing nephrons (corpuscular and tubular portion) showed the significant positive correlation (r = 0.85; p<0.01) with gestational age. CONCLUSION: The present study was one of few quantitative studies of the human developing nephron. Knowledge about the normal development of the human kidney should be important for the future medical practice. PMID 15889592


Human Nephron Number

<pubmed>16395270 12753298 12519920 1546799</pubmed>

Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States

Kidney Int. 2006 Feb;69(4):671-8.

Hughson MD, Douglas-Denton R, Bertram JF, Hoy WE. Source Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA. mhughson@pathology.umsmed.edu Abstract Low nephron number has been related to low birth weight and hypertension. In the southeastern United States, the estimated prevalence of chronic kidney disease due to hypertension is five times greater for African Americans than white subjects. This study investigates the relationships between total glomerular number (Nglom), blood pressure, and birth weight in southeastern African Americans and white subjects. Stereological estimates of Nglom were obtained using the physical disector/fractionator technique on autopsy kidneys from 62 African American and 60 white subjects 30-65 years of age. By medical history and recorded blood pressures, 41 African Americans, and 24 white subjects were identified as hypertensive and 21 African Americans and 36 white subjects as normotensive. Mean arterial blood pressure (MAP) was obtained on 81 and birth weights on 63 subjects. For African Americans, relationships between MAP, Nglom, and birth weight were not significant. For white subjects, they were as follows: MAP and Nglom (r=-0.4551, P=0.0047); Nglom and birth weight (r=0.5730, P=0.0022); MAP and birth weight (r=-0.4228, P=0.0377). For African Americans, average Nglom of 961 840+/-292 750 for normotensive and 867 358+/-341 958 for hypertensive patients were not significantly different (P=0.285). For white subjects, average Nglom of 923 377+/-256 391 for normotensive and 754 319+/-329 506 for hypertensive patients were significantly different (P=0.03). The data indicate that low nephron number and possibly low birth weight may play a role in the development of hypertension in white subjects but not African Americans. Comment in Hypertension, race, and glomeruli: more than simply a numbers game. [Kidney Int. 2006]

PMID 16395270

Glomerular number and size in autopsy kidneys: the relationship to birth weight

Kidney Int. 2003 Jun;63(6):2113-22.

Hughson M, Farris AB 3rd, Douglas-Denton R, Hoy WE, Bertram JF. Source University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA. mhughsn@pathology.umsmed.edu

Abstract

BACKGROUND: In the Southeast United States, African Americans have an estimated incidence of hypertension and end-stage renal disease (ESRD) that is five times greater than Caucasians. Higher rates of low birth weight (LBW) among African Americans is suggested to predispose African Americans to the higher risk, possibly by reducing the number of glomeruli that develop in the kidney. This study investigates the relationships between age, race, gender, total glomerular number (Nglom), mean glomerular volume (Vglom), body surface area (BSA), and birth weight. METHODS: Stereologic estimates of Nglom and Vglom were obtained using the physical disector/fractionator combination for autopsy kidneys from 37 African Americans and 19 Caucasians. RESULTS: Nglom was normally distributed and ranged from 227,327 to 1,825,380, an 8.0-fold difference. A direct linear relationship was observed between Nglom and birth weight (r = 0.423, P = 0.0012) with a regression coefficient that predicted an increase of 257,426 glomeruli per kilogram increase in birth weight (alpha = 0.050:0.908). Among adults there was a 4.9-fold range in Vglom, and in adults, Vglom was strongly and inversely correlated with Nglom (r =-0.640, P = 0.000002). Adult Vglom showed no significant correlation with BSA for males (r = -0.0150, P = 0.936), although it did for females (r = 0.606, P = 0.022). No racial differences in average Nglom or Vglom were observed. CONCLUSION: Birth weight is a strong determinant of Nglom and thereby of glomerular size in the postnatal kidney. The findings support the hypothesis that LBW by impairing nephron development is a risk factor for hypertension and ESRD in adulthood.

PMID 12753298

Nephron number in patients with primary hypertension

N Engl J Med. 2003 Jan 9;348(2):101-8.

Keller G, Zimmer G, Mall G, Ritz E, Amann K. Source Department of Pathology, University of Heidelberg, Heidelberg, Germany.

Abstract

BACKGROUND: A diminished number of nephrons has been proposed as one of the factors contributing to the development of primary hypertension. METHODS: To test this hypothesis, we used a three-dimensional stereologic method to compare the number and volume of glomeruli in 10 middle-aged white patients (age range, 35 to 59 years) with a history of primary hypertension or left ventricular hypertrophy (or both) and renal arteriolar lesions with the number and volume in 10 normotensive subjects matched for sex, age, height, and weight. All 20 subjects had died in accidents. RESULTS: Patients with hypertension had significantly fewer glomeruli per kidney than matched normotensive controls (median, 702,379 vs. 1,429,200). Patients with hypertension also had a significantly greater glomerular volume than did the controls (median, 6.50x10(-3) mm3 vs. 2.79x10(-3) mm3; P<0.001) but very few obsolescent glomeruli. CONCLUSIONS: The data support the hypothesis that the number of nephrons is reduced in white patients with primary hypertension. Copyright 2003 Massachusetts Medical Society Comment in Is microanatomy destiny? [N Engl J Med. 2003] Nephron number and primary hypertension. [N Engl J Med. 2003] Nephron number and primary hypertension. [N Engl J Med. 2003] Nephron number and primary hypertension. [N Engl J Med. 2003]

PMID 12519920

Glomerular number and size in relation to age, kidney weight, and body surface in normal man

Anat Rec. 1992 Feb;232(2):194-201.

Nyengaard JR, Bendtsen TF. Source Stereological Research Laboratory, Aarhus University, Denmark.

Abstract

The number and size of glomeruli in normal, mature human kidneys were estimated by a direct and unbiased stereological method, the fractionator. The number was 617,000 on average, and the mean size 6.0 M microns3. Both glomerular number and size showed significant negative correlation to age and significant positive correlation to kidney weight. Apparently, humans loose glomeruli with age. Body surface area correlated positively to kidney weight and total glomerular volume but not to number of glomeruli. Body surface area correlates significantly with metabolic rate (Robertson and Reid, Lancet, 1: 940-943, 1952). Thus, intraspecies adaptation of kidney filtration capacity to the metabolic demand is performed by changing the size of glomeruli, i.e., the number of glomeruli in individuals of a given species is independent of the metabolic rate.

PMID 1546799


Bladder

Endodermal origin of bladder trigone inferred from mesenchymal-epithelial interaction

J Urol. 2010 Jan;183(1):386-91.

Tanaka ST, Ishii K, Demarco RT, Pope JC 4th, Brock JW 3rd, Hayward SW.

Department of Urologic Surgery, Monroe Carell, Jr Children's Hospital at Vanderbilt, Nashville, Tennessee 37232-9820, USA. stacy.tanaka@vanderbilt.edu

Abstract PURPOSE: In the classic view of bladder development the trigone originates from the mesoderm derived wolffian ducts while the remainder of the bladder originates from the endoderm derived urogenital sinus. Recent molecular developmental studies have questioned the veracity of this received wisdom, suggesting an endodermal origin for the trigone. To shed further light on this issue we observed mesenchymal-epithelial interactions between trigone epithelium and fetal urogenital sinus mesenchyma to infer the trigonal germ layer of origin.

MATERIALS AND METHODS: Mouse trigone epithelium was recombined with fetal rat urogenital sinus mesenchyma in tissue recombinant grafts that were placed beneath the renal capsule of athymic mouse hosts. Grafts were harvested at 4 weeks. Control grafts with bladder dome and ureteral epithelium were also examined. Tissues were evaluated with hematoxylin and eosin, and Hoechst dye 33258 to confirm cell species origin. Immunohistochemistry was done with androgen receptor, broad spectrum uroplakin, dorsolateral prostate secretions and seminal vesicle secretions to differentiate prostatic and seminal vesicle differentiation.

RESULTS: Grafts of mouse trigone epithelium with fetal rat urogenital sinus mesenchyma yielded epithelial tissue that stained for dorsolateral prostate secretions but not for seminal vesicle secretions. Control grafts of bladder dome epithelium yielded the expected endodermal prostate differentiation. Control grafts of ureteral epithelium yielded the expected mesodermal seminal vesicle differentiation.

CONCLUSIONS: The consistent finding of prostatic epithelium in tissue recombinants of trigone epithelium and fetal urogenital sinus mesenchyma reinforces the hypothesis that the trigone is derived from the endoderm and not from the mesoderm, as commonly accepted.

PMID: 19914648 http://www.ncbi.nlm.nih.gov/pubmed/19914648

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794964

http://www.jurology.com/article/S0022-5347(09)02320-9/abstract