Kidneys proximal renal tubule

A family of integral proteins discovered by Peter Agre, the aquaporins (AQPs), provide channels for rapid movement of water molecules across all plasma membranes (Table 11-6 lists a few examples). Ten aquaporins are known in humans, each with its specialized role. Erythrocytes, which swell or shrink rapidly in response to abrupt changes in extracellular os-molarity as blood travels through the renal medulla, have a high density of aqua-porin in their plasma membranes (2 X 105 copies of AQP-1 per cell). In the nephron (the functional unit of the kidney), the plasma membranes of proximal renal tubule cells have five different aquaporin types. 

Although calcitriol is synthesized only in the proximal renal tubule, after the administration of pHJcalcidiol, radioactivity in the kidney accumulates only in the distal and collecting tubules. This is the region in which selective resorption of calcium from the urine occurs and, in response to calcitriol, there is induction of calbindin-D28k. As in the intestinal mucosa, calbindin in the kidney is a cytosolic protein and is presumably involved in the intracellular accumulation and transport of calcium. 

X-linked hypophosphatemic rickets is caused by abnormal reabsorption of phosphate in the proximal renal tubule, resulting in excessive excretion of phosphate and hence hypophosphatemia. There may also be blunting of the normal increase in calcidiol 1 -hydroxylase activity in response to hypophosphatemia. The gene responsible for the condition has been identified (the PHEX gene) its product is a membrane-bound endopeptidase that normally acts to clear the hormone phosphatonin from the circulation. Phosphatonin acts to decrease the activity of the sodium/phosphate cotransporter in the kidney (Drezner, 2000). 

Ullrich KJ, Rumrich G, Kloss S. Contralumlnal organic anion and cation transport in the proximal renal tubule V. Interaction with sulfamoyl- and phemoxy diuretics, and with p-lactam antibiotics. Kidney Int 1989 36(1) 78-88. 

Administration of Ga(N03)3 to rats led to tubular necrosis associated with the occlusion of renal tubular lumina with precipitates of gallium, calcium, and phosphate hypercalcuria was also evident (Newman et al. 1979). The nephrotoxicity and hypercalcuria were attenuated by administration of an osmotic diuretic. Patterns of protein synthesis in primary cultures of rat kidney proximal epithelial tubule cells were examined following exposure to GaClj (Aoki... 

Schali, Ch., F. Roch-Ramel Transport of urate and para-aminohippurate in isolated, nonperfused proximal renal tubules of the pig kidney. Kidney Int. 17 860-861 (1980b) (abstr.). 

An interesting type of physiological variation is the seasonal change observed in the kidney of the winter frog or the starved frog [155,156]. Proximal renal tubule cytochrome oxidase activity decreases markedly, in comparison to that of the summer frog. Structural changes appear in... 

Early kidney disease is difficult to detect. The urinalysis is normal in early lead nephropathy and the blood urea nitrogen and serum creatinine increase only when two-thirds of kidney function is lost. Measurement of creatinine clearance can often detect earlier disease as can other methods of measurement of glomerular filtration rate. An abnormal Ca-EDTA mobilization test has been used to differentiate between lead-induced and other nephropathies, but this procedure is not widely accepted. A form of Fanconi syndrome with aminoaciduria, glycosuria, and hyperphosphaturia indicating severe injury to the proximal renal tubules is occasionally seen in children. 

A few previous reports have suggested a connection between deferasirox and renal tubular damage. The prescribing package notes that the dose of deferasirox should be reduced if serum creatinine, a marker of kidney function and glomerular filtration, is elevated by more than 33% compared with serum creatinine prior to drug administration. Approximately 8% of deferasirox and its metabolites are excreted by the kidney, and previous in vitro studies have suggested that cells of the proximal renal tubule are sensitive to deferasirox toxicity. A case study was the first to provide biopsy evidence of deferasirox-mediated Fanconi syndrome [34 ]. 

Renal 1.9 3.9 (yellow protein in tubule lumen eosinophilic droplets in cells of proximal convoluted tubules increased kidney weights) 23.4 M (proteinuria) ... 

Schaub TP, Kartenbeck J, Konig J, Spring H, Dorsam J, Staehler G et al. Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma. J Am Soc Nephrol 1999 10(6) 1159—1169. 

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