Glomerular development

Podocalyxin is the main sialoprotein on the surface of the podocyte body and the apex of podocytes above the level of the slit diaphragms (K16). Podocalyxin activation can be demonstrated in the later phase of glomerular development and immediately precedes the formation of urinary spaces. Podocalyxin is a type I membrane protein with four potential N-glycosylated sites and many potential sites for... 

Abrahamson DR, St. John PL, Pillion DL, Tucker DC. Glomerular development in intraocular and intra renal grafts of fetal kidneys. Lab. Invest. 1991 64 629-639. 

Marshall, E.K. and Smith, H.W. (1930) The glomerular development of the vertebrate kidney in relation to habitat . Biological Bulletin, 59, 135-53. 

In Drosophila, Fat functions as a tumor suppressor gene and dachsous is involved in thorax, leg, and wing development. Several human and mouse homologs have been identified. FAT1 regulates actin filaments, and the Fail knockout leads to defects in glomerular slit formation [3]. 

In addition to excess sodium intake, abnormal renal sodium retention may be the primary event in the development of hypertension, and it includes abnormalities in the pressure-natriuresis mechanism. In hypertensive individuals, this theory proposes a shift in the control mechanism preventing the normalization of blood pressure. The mechanisms behind the resetting of the pressure-natriuresis curve may include afferent arteriolar vasoconstriction, decreased glomerular ultrafiltration, or an increase in tubular sodium reabsorption.4 Other theories supporting abnormal renal sodium retention suggest a congenital reduction in the number of nephrons, enhanced renin secretion from nephrons that are ischemic, or an acquired compensatory mechanism for renal sodium retention.9... 

Ischemic acute renal failure (ARF), characterized by a sharp decline of glomerular filtration rate, is a very common complication in hospitalized patients and particularly in patients with multiorgan failure. Although it develops most frequently in multimorbid patients, its occurrence per se increases the risk of death by 10- to 15-fold (Ghertow et al, 1998). This unacceptable situation in both diseases warrants the urgent development of new treatment modalities. 

NRC 1993 Vieira et al. 1996). Whether differences in xenobiotic metabolism make the child more or less suseeptible also depends on whether the relevant enzymes are involved in activation of the parent compound to its toxic form or in detoxification. There may also be differences in excretion, particularly in the newborn who has a low glomerular filtration rate and has not developed efficient tubular secretion and resorption capacities (Altman and Dittmer 1974 NRC 1993 West et al. 1948). Children and adults may differ in their capacity to repair damage Irom chemical insults. Children also have a longer lifetime in which to express damage Irom chemicals this potential is particularly relevant to cancer. 

In addition to other models [153], tubulointerstitial inflammation and fibrosis can be obtained by ureter obstruction. The inflammation develops very rapidly and is severe. The model is a good reflection of ureter obstruction in humans. However, a serious drawback in using this model for tubular drug delivery studies is the fact that glomerular filtration is absent. 

Jenkins et al. developed a capillary electrophoresis system for the measurement of iohexol as a marker of the glomerular filtration rate (GFR) with a run time of 5.25 min and a coefficient of variation (CV) of 4.3% at 80 mg L" [121]. The GFR, calculated from the plasma clearance, had a reproducibility of 5.47 %. A similar approach (liquid chromatography-mass spectrometry with positive electrospray ionization after enrichment by solid phase extraction) was applied by Putschew et al. for the determination of iodinated contrast agents in treatment plant effluents and surface waters [118]. 

Uric acid is the end product of the purine metabolism. When uric acid excretion via the kidneys is disturbed, gout can develop (see p. 190). Creatinine is derived from the muscle metabolism, where it arises spontaneously and irreversibly by cyclization of creatine and creatine phosphate (see p. 336). Since the amount of creatinine an individual excretes per day is constant (it is directly proportional to muscle mass), creatinine as an endogenous substance can be used to measure the glomerular filtration rate. The amount of amino acids excreted in free form is strongly dependent on the diet and on the ef ciency of liver function. Amino acid derivatives are also found in the urine (e.g., hippu-rate, a detoxification product of benzoic acid). 

Toxicity Aminoglycosides are associated with significant nephrotoxicity or ototoxicity. These agents are excreted primarily by glomerular filtration thus, the serum half-life will be prolonged and significant accumulation will occur in patients with impaired renal function. Toxicity may develop even with conventional doses, particularly in prerenal azotemia or impaired renal function. 

Glomerular capillary thrombosis Glomerular capillary thrombosis, which may result in graft failure, occasionally develops. 

Renal development is also immature in both the premature and the full-term baby. At birth overall renal function is approximately 20% of the adult value, but increases rapidly up to around one year of age when it is usually the same as that of an adult (when adjusted for body size). Glomerular filtration rate in particular may increase four-fold over the first week of life. As renal blood flow, glomerular filtration rate and tubular secretion of drugs are all low in the neonate, drugs cleared by the kidney need to be given in reduced dose - particularly if the drug has a narrow therapeutic window , and the potential to produce toxicity if Cp rises too greatly. 

Of practical importance is the problem of prescribing to the elderly, and to those with co-morbid conditions e.g. greater risk of serious gastroduodenal reactions, high risk of exacerbating cardiac failure and development of renal failure in patients dependent on prostaglandins to maintain glomerular perfusion, dehydration, concomitant use of ACE... 

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