In later life, mechanic, toxic, ischaemic and inflammatory insults can cause nephron damage and loss. In addition, nephron damage and loss can also result from persistent hyperfiltration as a result of an insufficient number of nephrons due to low nephron endowment or acquired nephron loss [ 4 , 5 ]. The latter illustrates the intricate interrelationship between nephron number and nephron damage.
The life cycle concept or womb to tomb concept draws
Intrauterine growth restriction IUGR is a well-known model for decreased nephron endowment [ 6 , 7 ]. During renal development, the kidney is formed by the interaction of two mesodermal-derived structures: the metanephric mesenchyme MM and the tubular ureteric bud UB. By reciprocal interaction, the MM induces the UB to grow and branch, whereas the UB induces the MM to subsequently form the pre-tubular aggregate which undergoes mesenchymal-epithelial transition and subsequently forms the immature stages of the nephron.
These nephrons finally become vascularized by the invasion of angioblasts forming the glomerulus and peritubular capillaries. The UB gives rise to the collecting duct and the urinary collection system, whereas the MM gives rise to the rest of the different nephron segments. Nephrogenesis ceases because of lack of replacement of non-induced MM at gestational week 32 in humans and within the 10 days after birth in mice and rats [ 9 ]. After nephrogenesis has ceased, renal function still increases by haemodynamic changes and nephron hypertrophy load-then-grow strategy [ 10 ].
Nephrons lost after cessation of nephrogenesis are not replaced. Although the exact mechanisms involved in the cessation of nephrogenesis are unknown, the final burst of nephrogenesis shortly after birth in mice appears to exhaust the progenitors in the cap of the MM in association with an increase in oxygenation that shifts progenitor activity from renewal to differentiation [ 11 , 12 ].
In this context, it is of note that in contrast to the postnatal situation, prenatal unilateral nephrectomy induced extended nephrogenesis in the contralateral kidney [ 13 ]. Finally, maternal dietary protein intake and specific amino acids might also be involved in the regulation of nephron endowment see below [ 14 ]. The Wilms tumour suppressor gene Wt1 plays a critical role in the regulation of early nephron formation by forcing the proliferating pluripotent MM cells to differentiate and exit the undifferentiated cell cycle [ 15 ].
A combination of alternative splicing, alternative translation sites and RNA editing leads to the expression of at least 24 different isoforms of Wt1. During nephrogenesis, Wt1 is expressed immediately after induction of the MM, and its expression becomes progressively restricted to the podocytes and parietal epithelial cells of Bowman's capsule [ 16—18 ].
The latter cells have recently been demonstrated to contain the podocyte progenitor cell population [ 19 ]. During nephrogenesis, Wt1 expression downregulates the genes involved in proliferation and the maintenance of non-induced MM-like six2, and induces the genes involved in podocytic differentiation e. As described above, nephrogenesis in humans ceases at gestational week 32, whereas in rodents nephrogenesis continues up to postnatal Day IUGR prior to the end of nephrogenesis in species where nephrogenesis is completed in utero causes a lower nephron endowment [ 1 ].
Preterm birth, when not associated with IUGR, is accompanied by normal nephron endowment, but there is a large increase in the incidence of abnormal glomeruli [ 24 ]. Because nephrogenesis is centrifugal, i. This has been extensively investigated in the baboon, a non-human primate model [ 25 ].
Furthermore, in extremely preterm infants postnatal nephrogenesis ceased after 40 days and always failed to realise normal nephron endowment [ 26 ].
The low-protein model of IUGR in the rat, even though not associated with preterm birth, does cause an increase in the incidence of abnormal glomeruli and a decreased nephron endowment [ 27 ]. This is probably because birth in the rat falls in the middle of the phase of nephrogenesis.
Thus, IUGR in rats, with respect to nephrogenesis, can be regarded as a model combining premature birth and IUGR, a situation in humans associated with a high incidence of abnormal glomeruli and reduced nephron endowment [ 28 ]. Another complicating factor of the model of maternal protein restriction is the fact that the effect of protein restriction on nephron development might be more complex than just a lack of building blocks for protein synthesis. Protein restriction not only reduces nephron endowment during nephrogenesis, protein overfeeding can also increase nephron endowment, suggesting that protein or amino acid consumption during nephrogenesis is directly involved in the regulation of nephron endowment [ 14 ].
In support of this, Jackson et al. Moreover, in adult humans, protein consumption is also directly related to nephron hypertrophy [ 5 ]. In contrast to the embryonic phase, postnatal growth restriction can assert a protective effect on the kidney. Extrauterine growth restriction can lower glomerular filtration rates GFRs in children born very preterm, which might be a beneficial adaptation in the long term [ 30 ].
In addition, although postnatal food restriction in rats leads to lower nephron numbers, protein restriction in lactation confers long-term nephroprotection in terms of albuminuria and NAG excretion [ 31 , 32 ].
CONFLICT OF INTEREST STATEMENT
Finally, despite a similar glomerular number, loss of renal function and hypertension in male rats after IUGR were more severe when these rats were subjected to postnatal overfeeding in comparison to a normal postnatal food intake [ 33 ]. Menendez-Castro et al.
The authors speculate that these alterations might, at least partially, result from primary dysregulation of Wt1 as a result of IUGR. Because the placenta provides most of the renal functions during intrauterine development, it appears unlikely that Wt1 abnormalities result from indirect effects of lower nephron endowment. Since Wt1 is involved in the regulation of nephrogenesis, it is conceivable that Wt1 alterations might not result from lower nephron endowment, but in contrast might be the cause of reduced nephron endowment. Wt1 abnormalities might, therefore, reflect the changes in developmental pathways resulting from maternal protein restriction subsequently causing a reduction of the nephrogenic zone and decreased nephron endowment.
After 70 days, Menendez-Castro et al. Dysregulation of Wt1 is associated with an increased risk of renal tumours, developmental disorders and glomerulosclerosis [ 34 ]. Interestingly, Wt1 is not only involved in nephron development but also in maintenance and repair. After glomerular damage in anti-GBM crescentic glomerulonephritis in mice and the passive Heymann nephritis model of membranous nephropathy in rats, Wt1 is upregulated in parietal epithelial cells of Bowman's capsule, which contain the podocyte progenitor cells [ 19 , 35 ].
However, such upregulation is not observed in murine focal segmental glomerulosclerosis induced by adriamycin, or the DOCA-salt model in rats [ 36 ]. It is, therefore, imaginable that the increased Wt1 expression in rats at Day 70 after maternal protein restriction does not reflect the cause of the glomerular injury, but rather the regenerative response to glomerular injury.
The glomerular injury might be the result of normalization and therefore, related to the relative increase in postnatal protein load in the IUGR mice. The mismatch of intrauterine nephron endowment and postnatal functional demand might damage the nephron, which subsequently induces the regenerative response. A project or idea that has no substance, but is sold as a great opportunity.
Suggested by Jim. A meeting scheduled after an event to discuss what was learned and assign blame for any problems. Suggested by Lafeerose. To talk in what the speaker believes to be an expressive manner, often using bizarre, contrived metaphors. Effective to the point of being lethal not actually lethal.
Endlessly analyzing a business's standpoint in terms of market share, profitability, growth potential, etc. Suggested by Alecia.
No matter how many times an instruction is repeated or simplified, this person will look back with glazed eyes, a blank expression and a predictable response, " The piloting room of a ship; the brain. A single, crucial moment on which success is dependent. The performance of a product after release, in the real world. This is where the rubber meets the road, people! Marks the point when a client approves a big contract. Just like announcing a new pope, if the pope were a cleared commission check.
What does cradle to grave contracting mean
Suggested by Bryan. To convey information by writing it out on a presentation surface. An issue that can only be addressed by the most senior of senior management. See: C-level. Suggested by einstein. A saturated and competitive market with no barriers to entry. It's a real whore's market.
To ensure that revenue rises faster than costs. Only by undertaking such an analysis is it possible to determine whether one solution carries a lower or higher environmental cost than another. Almost all major projects have some social impact. This may be the compulsory re-location of people living on land about to be submerged under a reservoir or a threat to the livelihood of small traders from the development of a hypermarket nearby.
Whole-life costing is a key component in the economic appraisal associated with evaluating asset acquisition proposals. An economic appraisal is generally a broader based assessment, considering benefits and indirect or intangible costs as well as direct costs. In this way, the whole-life costs and benefits of each option are considered and usually converted using discount rates into net present value costs and benefits.
This results in a benefit cost ratio for each option, usually compared to the "do-nothing" counterfactual. Typically the highest benefit-cost ratio option is chosen as the preferred option. Historically, asset investments have been based on expedient design and lowest cost construction.
- 90 Days of Spiritual Intimacy : A Devotional Pattern for the Facilitation of Spiritual and Personal Transformation.
- eBook - acxplxccold.ga?
- Dexter (Mistress & Master of Restraint Book 3);
- nephron number counts—from womb to tomb | Nephrology Dialysis Transplantation | Oxford Academic;
- Smashwords – IT Product Life Cycle Management: From the womb to the tomb – a book by Ike Ugochuku.
If such investment has been made without proper analysis of the standard of service required and the maintenance and intervention options available, the initial saving may result in increased expenditure throughout the asset's life. By using whole-life costs, this avoids issues with decisions being made based on the short-term costs of design and construction. Often the longer-term maintenance and operation costs can be a significant proportion of the whole-life cost. During the life of the asset, decisions about how to maintain and operate the asset need to be taken in context with the effect these activities might have on the residual life of the asset.
Although the general approach to determining whole-life costs is common to most types of asset, each asset will have specific issues to be considered and the detail of the assessment needs to be tailored to the importance and value of the asset. High cost assets and asset systems will likely have more detail, as will critical assets and asset systems. Maintenance expenditure can account for many times the initial cost of the asset. Although an asset may be constructed with a design life of 30 years, in reality it will possibly perform well beyond this design life.
- 1. Introduction?
- Use 'cradle to grave' in a Sentence?
- The Ridiculous Business Jargon Dictionary: W-words.
- Related Articles.
- WHEN TECHNOLOGY IS HANDLED,;
- Amazon Accounting and Management Book Links S-Z;
The appropriateness of the maintenance strategy must be questioned, the point of intervention for renewal must be challenged. The process requires proactive assessment which must be based on the performance expected of the asset, the consequences and probabilities of failures occurring, and the level of expenditure in maintenance to keep the service available and to avert disaster. Whole-life cost is often referred to as " total cost of ownership TCO " when applied to IT hardware and software acquisitions.