Glomerular

The principal organs involved in the peripheral clearance of hGH from the plasma are the kidney and fiver. hGH is cleared via glomerular filtration at the kidney and by a receptor-mediated mechanism at the fiver (58,59). In animal models, derivatives of hGH such as the 20,000 mol wt variant, oligomeric forms, and hGH complexed with GH-binding protein have been shown to be cleared from the semm at significandy lower rates than 22,000 mol wt hGH (60—62). The prolonged plasma half-life of these derivatives probably reflects a combination of decreased receptor affinity and size constraints on glomerular filtration. 

Kidney Function. Prostanoids influence a variety of kidney functions including renal blood flow, secretion of renin, glomerular filtration rate, and salt and water excretion. They do not have a critical role in modulating normal kidney function but play an important role when the kidney is under stress. Eor example, PGE2 and -I2 are renal vasodilators (70,71) and both are released as a result of various vasoconstrictor stimuli. They thus counterbalance the vasoconstrictor effects of the stimulus and prevent renal ischemia. The renal side effects of NSAIDS are primarily observed when normal kidney function is compromised. 

Technetium-99m mertiatide (A/-[Ai-[A/-[(benzoylthio)acetyl]glycyl]glycine) is a renal imaging agent. It is excreted by the kidneys via active tubular secretion and glomerular filtration. The kit vial is reconstituted by using 740—3700 MBq (20—100 mCi) of Tc pertechnetate and boiling for 10 minutes. 

The overall effect in most animals is to stimulate intestinal absorption of calcium with a concomitant increase in semm calcium and a reduction in parathyroid hormone (PTH). Modest hypercalcemia allows the glomerular filtration rate to remain stable and hypercalciuria to occur because of increased filtered load of calcium and reduction of tubular resorption of calcium with reduced PTH. However, with further increases in semm calcium, the glomerular filtration rate decreases, resulting in an even more rapid increase in semm calcium and the subsequent fall in urinary calcium. 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

Cadmium is effectively accumulated in the kidneys. When the cadmium concentration exceeds 200 gg/g in the kidney cortex, tubular damage will occur in 10% of the population, and proteins begin to leak into urine (proteinuria). When the concentration of cadmium in the kidney cortex exceeds 300 pg/g, the effect is seen in 50% of the exposed population. Typically, excretion of low-molecular weight proteins, such as beta-microglobulin, is increased, due to dysfunction of proximal tubular cells of the kidney. The existence of albumin or other high-molecular weight proteins in the urine indicates that a glomerular injury has also taken place. The excretion of protein-bound cadmium will also be increased. 

Aldosterone, the most potent of the mineralocorticoids (Figure 25.43), is involved in the regulation of sodium and potassium balances in tissues. Aldosterone increases the kidney s capacity to absorb Na, Cl, and HgO from the glomerular filtrate in the kidney tubules. 

In the kidney, ANG II reduces renal blood flow and constricts preferentially the efferent arteriole of the glomerulus with the result of increased glomerular filtration pressure. ANG II further enhances renal sodium and water reabsorption at the proximal tubulus. ACE inhibitors thus increase renal blood flow and decrease sodium and water retention. Furthermore, ACE inhibitors are nephroprotective, delaying the progression of glomerulosclerosis. This also appears to be a result of reduced ANG II levels and is at least partially independent from pressure reduction. On the other hand, ACE inhibitors decrease glomerular filtration pressure due to the lack of ANG II-mediated constriction of the efferent arterioles. Thus, one important undesired effect of ACE inhibitors is impaired glomerular filtration rate and impaired kidney function. 

In the kidney, bradykinin increases renal blood flow, whereas glomerular filtration rate remains unaffected. 

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]. 

As a general rule, increases of renal blood flow and/ or glomerular filtration rate (GFR) correlate rather well with increased urinary excretion of solutes and water. The underlying causes for this correlation are not fully understood, but they reflect incomplete adjustments of tubular reabsorption to an increase of tubular electrolyte load. 

Glomerular filtration rate (GFR) is the volume of plasma-like fluid that is filtered per unit time across the glomerular capillary membranes to enter the tubular space. Filtrate formation is driven by the net filtration pressure that is equal to the capillary hydrostatic pressure diminished by the sum of capillary oncotic... 

The macula densa is a dense aggregation of cells in the distal tubule of nephrons facing the glomerular tuft of capillaries. These cells sense the salt content of the distal tubular fluid and adjust glomerular perfusion and renin secretion accordingly. 

Luzius Dettli was not only the first who described the linear function for the dependence of diug elimination on glomerular filtration rate. He was also the first who proposed the fundamental dose adjustment recommendation, the proportional dose reduction rule. Two alternatives are given to either reduce the single dose (D) or extend the interval (Tau). 

Urographic contrast agents are contrast agents which possess the characteristics of very little enteral absotp-tion, almost no protein binding or uptake into cells, an extracellular (interstitial) distribution and glomerular filtration. These pharmacokinetics are due to very little interaction with the organism, resulting in very low toxicity, preferably nonionic (neutral) molecules. 

Decreased serum proteins Decreased renal mass, blood flow, and glomerular filtration rate... 

These studies led to the realization that proteinuria— the abnormal appearance of protein in the urine— could result not only from the enlargement of submicroscopic holes in the glomerular capillary wall, but also from the loss or neutralization of its negatively charged components. This finding has provided a new direction for research on the molecular basis for the nephrotic syndrome, a group of kidney diseases all characterized by massive proteinuria. 

F (shrunken glomerular tufts necrosis of tubular epithelial cells)... 

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