In Search of Imprints Left by the Impairment of Nephrogenesis

2019 ◽  
Vol 207 (2) ◽  
pp. 69-82 ◽  
Author(s):  
Will W. Minuth
Keyword(s):  
Late Phase ◽  
Human Kidney ◽  
Late Gestation ◽  
Clinical Aspects ◽  
Pathological Findings ◽  
Fetal Kidney ◽  
Outer Cortex ◽  
Low Birth Weight Babies ◽  
Fetal Human Kidney ◽  
Nephrogenic Zone

Clinical aspects dealing with the impairment of nephrogenesis in preterm and low birth weight babies were intensely researched. In this context it was shown that quite different noxae can harm nephron formation, and that the morphological damage in the fetal kidney is rather complex. Some pathological findings show that the impairment leads to changes in developing glomeruli that are restricted to the maturation zone of the outer cortex in the fetal human kidney. Other data show also imprints on the stages of nephron anlage including the niche, the pretubular aggregate, the renal vesicle, and comma- and S-shaped bodies located in the overlying nephrogenic zone of the rodent and human kidneys. During our investigations it was noticed that the stages of nephron anlage in the fetal human kidney during the phase of late gestation have not been described in detail. To contribute, these stages were recorded along with corresponding images. The initial nephron formation in the rodent kidney served as a reference. Finally, the known imprints left by the impairment in both specimens were listed and discussed. In sum, the relatively paucity of data on nephron formation in the fetal human kidney during the late phase of gestation is a call to start with intense research so that concepts for a therapeutic prolongation of nephrogenesis can be designed.

scholarly journals Histogenesis of human fetal kidney from 14 weeks to 36 weeks: a study

2019 ◽  
Vol 7 (11) ◽  
pp. 4330
Author(s):  
Divya Jain Pokarna ◽  
K. Kshitija ◽  
Seethamsetty Saritha
Keyword(s):  
Human Kidney ◽  
Loop Of Henle ◽  
Fetal Kidney ◽  
Developmental Anatomy ◽  
Corticomedullary Junction ◽  
Kidney Morphology ◽  
Well Differentiated ◽  
Collecting Tubules ◽  
Fetal Human Kidney ◽  
Nephrogenic Zone

Background: The knowledge of fetal human Kidney morphology and developmental anatomy is very important for prenatal diagnosis of disorders such as Wilm’s tumor, hydronephroses and congenital malformation etc.Methods: The study was carried out on 40 kidneys procured from 20 spontaneously aborted fetuses (11males and 9 females) ranging from 14wks-36wks of gestation, after confirming their age through  CRL they were grouped and then processed to form slides and stained with haemtoxylin and eosin and seen under light microscope.Results: All kidneys were lobulated at early gestational age and became fused by 36 wks. Corticomedullary junction and preformed collecting tubules were seen clearly by 18wks. Well differentiated PCT and DCT were formed by 19-23 wks. Well-formed pyramids by 28 wks and medullary rays by 29 weeks were clearly distinguished. Loop of Henle developed and distinguished by 28 wks. Increased vascularity was seen by 32-36 wks. Nephrogenic zone and undifferentiated mesenchyme decreased and matured glomeruli increased by 36 wks.Conclusions: The present study gave emphasis to the development of each component in medulla and cortex of kidney.  

scholarly journals The mutual patterning between the developing nephron and its covering tissues—valid reasons to rethink the search for traces left by impaired nephrogenesis

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Will W. Minuth
Keyword(s):  
Collecting Duct ◽  
Human Kidney ◽  
Later Life ◽  
Optical Microscope ◽  
Late Gestation ◽  
Morphological Data ◽  
Present Contribution ◽  
The Individual ◽  
Fetal Human Kidney ◽  
Nephrogenic Zone

Abstract Background The impairment of nephrogenesis can cause the termination of nephron formation in preterm and low birth weight babies. This leads to oligonephropathy with severe health consequences in later life. Although many clinical parameters are known, surprisingly little information is available regarding the initial damage on the developing nephron. Equally astounding, the first morphological data regarding the specifics of nephron formation in the nephrogenic zone of the fetal human kidney during late gestation has only been published within the past few years. In this context, it was observed that each stage of nephron anlage is surrounded by a specific set of tissues. Although highly relevant for the normal progress of nephron formation, the mutual patterning has not been systematically described. Results To contribute, the different stages of nephron anlage in the nephrogenic zone of the fetal human kidney during late gestation were screened by the optical microscope and documented by images. Following this, magnifications (28 × 18 cm) were produced to trace the contours of the developing nephron and its covering tissues. The resulting sketches, almost true to scale, were scanned, edited, and processed by a design program. As a base, first the individual position, size, and shape of the nephrogenic niche, pretubular aggregate, renal vesicles, comma- and S-shaped bodies are presented. Secondly, their structural relations to the renal capsule, collecting duct ampulla, perforating radiate artery, and expanding interstitium are shown. Third of all, the focus is on less considered configurations, such as site-specific approximation, local distancing, punctual adhesion, integration, separation, delamination, formation of congruent and divergent surfaces, and folding and opening of interstitial clefts. Conclusions The present contribution illuminates the mutual patterning between the developing nephron and its covering tissues. It is indispensable to know about the microanatomical relations, in order to identify whether the noxae impairing nephrogenesis targets only the developing nephron or also its covering tissues as interacting and controlling instances.

scholarly journals Action Plan for Prolongation of Nephrogenesis in Preterm and Growth Restricted Babies: Explore Ultrastructure of the Nephrogenic Zone, Identify a Molecular Target, Select a Viable Drug and Find a Path for Administration

Drug Research ◽  
2017 ◽  
Vol 68 (01) ◽  
pp. 5-16 ◽  
Author(s):  
Will Minuth
Keyword(s):  
Kidney Development ◽  
Developmental Process ◽  
Action Plan ◽  
Late Phase ◽  
Cell Communication ◽  
Decisive Role ◽  
Human Kidney ◽  
Few Data ◽  
Stem Cell Niches ◽  
Nephrogenic Zone

AbstractA large amount of investigations informs about primary steps of mammalian kidney development such as anlage of the organ and initial nephron formation, while only few data exists about the late phase of human kidney development. In particular, little attention was up to date addressed to the decrease of morphogenic activity in the nephrogenic zone short before birth and the vanishing of all stem cell niches aligned beyond the organ capsule. There is evidence that molecular controlling of this normal but degenerative developmental process also plays a decisive role in the kidneys of preterm and growth restricted babies. Although they are born in a phase of active nephrogenesis, a substantial percentage of them evolves oligonephropathy, formation of atypical glomeruli and immaturity of parenchyma. Pathologic findings point out that independent from chemical nature all suspected hampering influences sublimate in the nephrogenic zone. However, it is unknown, whether impaired nephrogenesis is locally caused by harming interstitial fluid, disturbance of morphogen signaling, unbalanced synthesis of extracellular matrix or limited cell to cell communication. Thus, first of all these issues must be resolved, then save application of medicines prolonging nephrogenesis waits for realization. Due to the unexpectedly complex microanatomy and physiology of the nephrogenic zone, it will be a particular challenge for the future.

scholarly journals Quantitative analysis of the nephron during human fetal kidney development

2005 ◽  
Vol 62 (4) ◽  
pp. 281-286 ◽  
Author(s):  
Marija Dakovic-Bjelakovic ◽  
Slobodan Vlajkovic ◽  
Rade Cukuranovic ◽  
Svetlana Antic ◽  
Goran Bjelakovic ◽  
...  
Keyword(s):  
Gestational Age ◽  
Kidney Development ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Volume Density ◽  
Ureteric Bud ◽  
Fetal Kidney ◽  
Intrauterine Development ◽  
Human Fetal Kidney ◽  
Nephrogenic Zone

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 analyzed. 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.

Expression of the potassium channel ROMK in adult and fetal human kidney

2005 ◽  
Vol 123 (6) ◽  
pp. 553-559 ◽  
Author(s):  
Rolf M. Nüsing ◽  
Fiore Pantalone ◽  
Hermann-Josef Gröne ◽  
Hannsjörg W. Seyberth ◽  
Markus Wegmann
Keyword(s):  
Potassium Channel ◽  
Human Kidney ◽  
Fetal Human Kidney

Low vascularization of the nephrogenic zone of the fetal kidney suggests a major role for hypoxia in human nephrogenesis

2017 ◽  
Vol 49 (9) ◽  
pp. 1621-1625 ◽  
Author(s):  
C. Gerosa ◽  
D. Fanni ◽  
A. Faa ◽  
P. Van Eyken ◽  
A. Ravarino ◽  
...  
Keyword(s):  
Fetal Kidney ◽  
Nephrogenic Zone

scholarly journals Caspase-independent programmed cell death triggers Ca2PO4 deposition in an in vitro model of nephrocalcinosis

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Giovanna Priante ◽  
Federica Quaggio ◽  
Lisa Gianesello ◽  
Monica Ceol ◽  
Rosalba Cristofaro ◽  
...  
Keyword(s):  
Cell Death ◽  
Late Phase ◽  
Annexin V ◽  
Human Kidney ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Death Process ◽  
Osteogenic Medium ◽  
Medullary Nephrocalcinosis ◽  
Calcification Process

Nephrocalcinosis involves the deposition of microscopic crystals in the tubular lumen or interstitium. While the clinical, biochemical, and genetic aspects of the diseases causing nephrocalcinosis have been elucidated, little is known about the cellular events in this calcification process. We previously reported a phenomenon involving the spontaneous formation of Ca2PO4 nodules in primary papillary renal cells from a patient with medullary nephrocalcinosis harboring a rare glial cell-derived neurotrophic factor (GDNF) gene variant. We also demonstrated that cultivating GDNF-silenced human kidney-2 (HK-2) cells in osteogenic conditions for 15 days triggered Ca2PO4 deposits. Given the reportedly close relationship between cell death and pathological calcification, aim of the present study was to investigate whether apoptosis is involved in the calcification of GDNF-silenced HK-2 cells under osteogenic conditions. Silenced and control cells were cultured in standard and osteogenic medium for 1, 5, and 15 days, and any Ca2PO4 deposition was identified by means of von Kossa staining and environmental SEM (ESEM) analyses. Based on the results of annexin V and propidium iodide (PI) analysis, and terminal deoxynucleotidyl transferase dUTP-biotin nick end labeling (TUNEL) assay, the silenced cells in the osteogenic medium showed a significant increase in the percentage of cells in the late phase of apoptosis and an increased Ca2PO4 deposition at 15 days. The results of quantitative real-time PCR (qRT-PCR) of BAX and BCL2, and in-cell Western analysis of caspases indicated that the cell death process was independent of caspase-3, -6, -7, and -9 activation, however. Using this model, we provide evidence of caspase-independent cell death triggering the calcification process in GDNF-silenced HK-2 cells.

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