Renal tubule cells

Type 1 Von Gierke s disease Deficiency of glucose-6-phosphatase Liver cells and renal tubule cells loaded with glycogen. Hypoglycemia, lactic-acidemia, ketosis, hyperlipemia. 

Amphotericin B-induced ARF occurs in as many as 40% to 65% of patients treated with the conventional desoxycholate formulation.30 Nephrotoxicity is due to renal arterial vasoconstriction and distal renal tubule cell damage. Risk factors include high doses, treatment for at least 7 days, preexisting kidney dysfunction, and concomitant use of other nephrotoxic drugs.31 Three lipid-based formulations of amphotericin B have been developed in an attempt to decrease the incidence of ARF amphotericin B lipid complex, amphotericin colloidal dispersion, and liposomal amphotericin B. The range of... 

The possible mechanism kidney-induced hypertension is discussed in Section 2.4.2, Mechanisms of Toxicity. Lead appears to affect vitamin D metabolism in renal tubule cells, such that circulating levels of the vitamin D hormone, 1,25-dihydroxyvitamin D, are reduced. This effect is discussed later in this section under Other Systemic Effects. 

Part of the metabolic machinery of an osteoclast resembles the red cell and the renal tubule cells because all of these cell types contain the enzyme carbonic anhydrase (carbonate dehydratase) which generates acid, that is protons, and have ion pumps in their plasma membranes. The mechanism of bone resorption requires the action of cathepsin and metalloproteinase-9 working in an acidic environment (Figure 9.8). 

In short-term renal toxicity studies in rats gavage administration of 1,1,2,2-tetra-chloroethane caused renal toxicity as evidenced by an increased renal tubule cell labeling index, indicating replicative DNA synthesis. In 2-year studies 1,1,2,2-tetrachloroethane administered by gavage produced an increased incidence of hepatocellular carcinomas in mice but not in rats. In one epidemiological study of exposed army workers there was a slight increase in deaths due to genital cancer and leukemia. Exposure levels were not available,... 

HC03 in the membranes of renal tubule cells and the RBCs. 

Almost all diuretics exert their action at the luminal surface of the renal tubule cells. Their mechanism of action includes interaction with specific membrane transport proteins like thiazides, furosemide etc., osmotic effects which prevent the water permeable segments of the nephron from absorbing water like mannitol, and specific interaction with enzyme like carbonic anhydrase inhibitors i.e. acetazolamide, and hormone receptors in renal epithelial cells like spironolactone. 

Vasopressin activates two subtypes of G protein-coupled receptors (see Chapter 17). Vi receptors are found on vascular smooth muscle cells and mediate vasoconstriction. V2 receptors are found on renal tubule cells and reduce diuresis through increased water permeability and water resorption in the collecting tubules. Extrarenal V2-like receptors regulate the release of coagulation factor VIII and von Willebrand factor. 

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. 

FIGURE 29-5 Effect of aldosterone on renal tubule cells. CO Aldosterone CAD enters the cell and binds to a cytosolic receptor CR], creating an activated hormone-receptor complex CA-R],... 

The actions of P-gp located on the cell surface that act to restrict substrate access and to enhance elimination via efflux directed from cytoplasm to extracellular milieu are the most widely studied and understood. The remainder of this section will focus on the ramifications of the P-gp activity at the cell membrane level to disposition, which has been shown to be particularly relevant in barrier tissues such as the intestine, BBB, and blood-testes barrier, and in cells of eliminating organs such as hepatocytes and renal tubule cells. 

Berry JP, Hourdry J, Galle P, et al. 1978. Chromium concentration by proximal renal tubule cells An ultrastructural microanalytical and cytochemical study. J Histochem Cytochem 26 651-657. 

Aperia A, Fryckstedt J, Svensson L, Hemmings HC, Jr., Nairn AC, Greengard P (1991) Phosphorylated Mr 32,000 dopamine- and cAMP-regulated phosphoprotein inhibits Na+,K<+)-ATPase activity in renal tubule cells. Proc Natl Acad Sci USA 55 2798-2801. 

These are structurally related to penicillins and are excreted predominantly by renal tubular secretion. The risk of seizures with imipenem is 0.2%. They are toxic to the proximal renal tubule cells. 

Absorption across the skin is probably slight and methods of pesticide use rarely include a hazard of inhalation, but uptake of ingested fluoride by the gut is efficient and potentially lethal. Excretion is chiefly in the urine renal clearance of fluoride from the blood is rapid. However, large loads of absorbed fluoride poison renal tubule cells. Functional tubular disturbances and sometimes acute renal failure result. 

Inhibition of transport processes that carry substances across cells, e.g. blockade of anion transport in the renal tubule cell by probenecid can be used to delay excretion of penicillin, and to enhance elimination of mate... 

Humes HD, Cieslinski DA, Coimbra TM, Messana JM, GalvaoC. Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure. Journal of Clinical Investigations 84 1757-61,1989. 

Springate J and Taub M. Ifosfamide toxicity In cultured proximal renal tubule cells. Pediatr Nephrol 22 358-365,2007. 

Hauser lA, Koziolek M, Hopfer U, and Thevenod F. Therapeutic concentrations of cyclosporine A, but not FK506, increase P-glycoprotein expression in endothelial and renal tubule cells. Kidney Int 54 1139-1149,1998. 

Sorokina EJ, Wesson JA, Kleinman JG. An acidic peptide sequence of nucleolin-related protein mediate the attachement of calcium oxalate to renal tubule cells. J.Am.Soc.Nephrol. 2004 15 2057-65. 

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