Tubular leakage

Donohoe JF, Venkatachalam MA, Bernard DB, Levinsky NG Tubular leakage and obstruction after renal ischemia structural-functional correlations. Kidney Int. 13 208-222,1978... 

Why is the hypothesis of tubular leakage as a cause of acute renal failure not considei valid ... 

Due to size limitations, most enzymes present in plasma are not filtered into the urine but there are some exceptions (e.g., lysozyme) these will be increased in the urine if tubular function (and uptake of filtered protein) is decreased. In addition, if glomerular injury accompanies tubular injury leakage of larger molecular weight proteins may occur and plasma source enzymes that ordinarily would not be filtered may appear in urine. AST, LDH and IALP may thus appear in urine. 

The porosity at both ends of a tubular or monolithic honeycomb membrane element can be a potential source of leakage. These extremities need to be made impervious to both permeates and retentates so that the two streams do not remix. Typically the end surfaces and the outer surfaces near the ends of a commercial membrane element are coated with some impervious enamel or ceramic materials. 

Cyclic GMP decreases basal and stimulated concentrations of intracellular Ca (Nakashima et al, 1986 Johansson and Haynes, 1992). A number of Ca handling systems have been identified in platelets including receptor operated channels, passive leak, Ca -ATPase extrusion pump, the NaV Ca exchanger, Ca -accumulating ATPase pump of the dense tubular membrane (an intraplatelet membrane Ca store) and passive leakage and receptor operated Ca chatinels in the dense tubular membrane. In principle, all these... 

Mild and uncomplicated hyperkalemia is commonly observed in patients taking ciclosporin and is generally prevented by a low potassium diet. A reduction in distal nephron potassium secretion and tubular flow rate, with insensitivity to exogenous mineralocorticoids, and leakage of cellular potassium into the extracellular fluid are possible mechanisms (SED-13, 1124) (64). 

The cell membrane serves as a protective barrier in renal cells. It is the initial site which p-lactams encounter in their journey to the cellular environment from the blood or tubular fluid, p-lactams may disrupt the functional organization of the membrane through peroxidation of membrane lipids, which, in turn, leads to the inability of membrane to serve as an osmotic barrier and causes the cytosol contents to leak. As a result of the cephalosporins disruptive effect on cell membrane, increased leakage of the cytosolic enzyme lactate dehydrogenase (LDH) occurs. The increased LDH concentration was from the cytosol of the renal cortex [49,71] or from isolated proximal and distal tubular cells [39] or in the urine of experimental animals [39]. The results of these studies indicate that plasma membrane became permeable to large molecules such as LDH. After cephalosporin treatment, cephaloridine caused the greatest decrease of LDH concentration in cytosol [49]. Whereas, cephaloridine induced a greater release of LDH from proximal tubular cells than cepha-lothin and cephalexin, distal cells were not affected by any of these cephalosporins [38,39]. 

Lead exposure may cause kidney damage (Lim et al. 2001). In acute lead toxicity, there is proximal tubular damage, which may result in a reversible Fanconi syndrome-like condition with aminoaciduria, glucosuria, and hyperphosphaturia. Further, the tubular damage may cause leakage of enzymes (e.g., lysosomal NAG) from the cells into the urine (Skerfving 1993) at B-Pbs in the range 1.5-2.0 pmolL. This effect may be reversible. 

II vivo and in hepatocytes, as shown by inhibition of super-oxide dismuiase (SOD) activity, enhanced malondialdehyde production, LDH leakage, and a decrease in glutathione peroxidase activity (Julka et ai, 1992). OP intoxication has also been shown to induce oxidative stress at the tubular level and may play a role in the pathogenesis of acute tubular necrosis (Poovala etciL, 1999). 

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