S- nephrotoxicity

Hori R, Shimakura M, Aramata Y, Kizawa K, Nozawa l,Takahata M, Minami S. Nephrotoxicity of piperacillin combined with furo-semide in rats. Jpn J Antibiot 2000 53(8) 582-591. 

Behr TM, Behe M, Kluge G, Gotthardt M, Schipper ML, Gratz S. Nephrotoxicity versus... 

The exact mechanism(s) responsible for fluoride s nephrotoxicity remain to be defined. The fluoride ion interferes with normal cell function on several levels. Fluoride is an inhibitor of several cellular enzyme systems and dirninishes tissue respiration and anaerobic glycolysis [89]. In the kidney, fluoride interferes with transport of sodium in the proximal convoluted tubule. It also inhibits adenylate cyclase in the collecting system and dirninishes the action of antidiuretic hormone. Experimental evidence in rats indicates that the chloride dependent pump, in the thick ascending part of Henle s loop, also is inhibited [90]. In human collecting duct cell cultures, exposure to fluoride ions inhib-... 

Buchholtz K, Larsen CT, Hassager C, Bruun NE. Severity of gentamicin s nephrotoxic effect on patients with infective endocarditis a prospective observational cohort study of 373 patients. Clin Infect Dis 2009 48(1) 65-71. 

Gapreomycin, Viomycin, and Enviomycin. Capreomycin (Capastat, Lilly), a bacteriostatic, antimycobacterial peptide mixture isolated from Streptomjces capreolus was first reported in 1961 (106—108). This tuberactinomycin family member, shown in Table 4, was introduced into the U.S. market in 1971 where it has remained a usehil but nephrotoxic and ototoxic second-line alternative to first-line tuberculosis therapies. Because capreomycin is somewhat less toxic than viomycin (tuberoactinomycin B [32988-50-4]) C25H42N23O2Q (109,110), capreomycin has now displaced viomycin in the United States and most other markets. The stmcture of viomycin is shown in Figure 2. The related enviomycin (tuberactinomycin N [33103-22-9]), C23H43N23O2Q,... 

The first human kidney and bone marrow transplants using cyclosporine were reported in 1978. Oral or intravenous cyclosporine is an immunosuppressant for transplantation of these and other organs and investigations are underway for its possible use in a variety of autoimmune diseases including rheumatoid arthritis, severe psoriasis, and Crohn s disease. Dose-dependent nephrotoxicity (261—264) remains the primary limitation of the dmg and necessitates close monitoring of patients, including measurement of dmg levels in blood. Cyclosporine research has been reviewed (265—274). 

INEFFECTIVE TISSUE PERFUSION RENAL The patient taking an aminoglycoside is at risk for nephrotoxicity. The nurse measures and records the intake and output and notifies the primary health care provider if the output is less than 750 ml/day. It is important to keep a record of the fluid intake and output as well as a daily weight to assess hydration and renal function. The nurse encourages fluid intake to 2000 ml/day (if the patient s condition permits). Any changes in the intake and output ratio or in the appearance of the urine may indicate nephrotoxicity. The nurse reports these types of changes to the primary health care provider promptly. The primary health care provider may order daily laboratory tests (ie, serum creatinine and blood urea nitrogen [BUN]) to monitor renal function. The nurse reports any elevation in the creatinine or BUN level to tiie primary health care provider because an elevation may indicate renal dysfunction. 

The nurse must carefully monitor fluid intake and output because this drug may be nephrotoxic (harmful to the kidneys). In some instances, the nurse may need to perform hourly measurements of the urinary output. Periodic laboratory tests are usually ordered to monitor the patient s response to therapy and detect toxic drug reactions. 

Human immune globulin intravenous (IGIV) products have been associated with renal impairment, acute renal failure, osmotic nephros s and death. Individuals with a predication to acute renal failure, such as those with preexisting renal disease, diabetes mellitus individuals older than 65 years or patients receiving nephrotoxic drugs should not be given human IGIV products... 

Ali, B.H. AI Moundhri, M.S. (2006). Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compoimds a review of some recent research. Food and Chemical Toxicology, Vol. 44, No.8, (August 2006), pp. 1173-1183, ISSN 0278-6915. 

Bimer G, Vamvakas S, Dekant W, et al. 1993. Nephrotoxic and genotoxic N-acetyl-S-dichlorovinyl-L-cysteine is a urinary metabolite after occupational 1,1,2-trichloroethene exposure in humans Implications for the risk of trichloroethene exposure. Environ Health Perspect 99 281-284. 

Elfarra AA, Jakobson 1, Anders MW. 1986. Mechanism of S-(l,2-dichlorovinyl)glutathione-induced nephrotoxicity. Biochem Pharmacol 35 283-288. 

Sirolimus is currently the only FDA-approved ToR inhibitor. One of its derivatives, everolimus, is in phase III clinical trials and has been approved for use in some European countries.30 Sirolimus is a macrolide antibiotic that has no effect on cal-cineurin phosphatase.11,31,32 Sirolimus inhibits T cell activation and proliferation by binding to and inhibiting the activation of the mammalian ToR, which suppresses cellular response to IL-2 and other cytokines (i.e., IL-4 and IL-15J.11,31 Studies have shown that sirolimus may be used safely and effectively with either cyclosporine or tacrolimus as a replacement for either azathioprine or mycophenolate mofetil.33 However, when using both sirolimus and cyclosporine as part of a patient s immunosuppressant therapy, because of a drug interaction between the two resulting in a marked increase in sirolimus concentrations, it is recommended to separate the sirolimus and cyclosporine doses by at least 4 hours. Sirolimus also can be used as an alternative agent for patients who do not tolerate calcineurin inhibitors due to nephrotoxicity or other adverse events.34... 

Aicher, L., Wahl, D., Arce, A., Grenet, O., and Steiner, S. (1998). New insights into cyclosporine A nephrotoxicity by proteome analysis. Electrophoresis 19, 1998-2003. 

Rouisse L, Chakrabarti S, Tuchweber B. 1986. Acute nephrotoxic potential of acrylonitrile in Fischer-344 rats. Res Commun Chem Pathol Pharmacol 53 347-360. 

Venugopal, N.B.R.K. and S.L.N. Reddy. 1992b. Nephrotoxic and hepatotoxic effects of bivalent and hexavalent chromium in a teleost fish Anabas scandens enzymological and biochemical changes. Ecotoxicol. Environ. Safety 24 287-293. 

Liu, X.Y., T.Y. Jin, G.F. Nordberg, S. Ranner, M. Sjostrom, and Y. Zhou. 1992. A multivariate study of protective effects of Zn and Cu against nephrotoxicity induced by cadmium metallothionein in rats. Toxicol. Appi. Pharmacol. 114 239-245. 

Goldstein, R.S., Noordewier, B., Bond, J.T., Hook, J.B. and Mayor, G.H. (1981). Cis-diaminedichloroplatinum nephrotoxicity Time course and dose response of renal functional impairment. Toxicol. Appl. Pharmacol. 60 163-175. 

Goldstein, R.S., Pasino, D.A., Hewitt, W.R. and Hook, J.B. (1986). Biochemical mechanisms of cephaloridine nephrotoxicity Time and concentration dependence of peroxidative injury. Toxicol. Appl. Pharmacol. 83(2) 261-270. 

Hori, R., Yamamoto, S., H., Kohno, M. and Inui, K. (1984). Effect of aminoglycoside antibiotics on cellular functions of kidney epithelial cell line (LLC-PKi) a model system for aminoglycoside nephrotoxicity. Pharmacol. Exp. Ther. 230 742-748. 

Kacew, S. and Hirsch, G.H. (1981). Evaluation of nephrotoxicity of various compounds by means of in vitro techniques and comparison to in vivo methods. In Toxicology of the Kidney (Hook, J.B., Ed.). Raven Press, New York, pp. 77-98. 

Smith, J.H., Maita, K., Sleight, S.D. and Hook, J.B. (1983). Mechanism of chloroform nephrotoxicity. I. Time course of chloroform toxicity in male and female mice. Toxicol. Appl. Pharmacol. 70 467-479. 

S. G. E. Hart, W. P. Beierschmitt, J. B. Bartolone, D. S. Wyand, E. A. Kharrallah, S. D. Cohen, Evidence Against Deacetylation and for Cytochrome P450-Mediated Activation in Acetaminophen-Induced Nephrotoxicity in the CD-I Mouse , Toxicol. Appl. Pharmacol. 1991, 107, 1-15. 

Covalent protein adducts of quinones are formed through Mchael-type addihon reachon with protein sulfhydryl groups or glutathione. Metabolic activahon of several toxins (e.g., naphthalene, pentachlorophenol, and benzene) into quinones has been shown to result in protein quinone adducts (Lin et al, 1997 Rappaport et al, 1996 Zheng et al., 1997). Conversion of substituted hydroquinones such as p-aminophenol-hydroquinone and 2-bromo-hydroquinone to their respective glutathione S-conjugates must occur to allow bioactivation into nephrotoxic metabolites (Dekant, 1993). Western blot analysis of proteins from the kidneys of rats treated with 2-bromo-hydroquinone has revealed three distinct protein adducts conjugated to quinone-thioethers (Kleiner et al, 1998). 

D-penidllamine can promote the elimination of copper (e.g., in Wilson s disease) and of lead ions. It can be given orally. Two additional uses are cystinu-ria and rheumatoid arthritis. In the former, formation of cystine stones in the urinary tract is prevented because the drug can form a disulfide with cysteine that is readily soluble. In the latter, penicillamine can be used as a basal regimen (p. 320). The therapeutic effect may result in part from a reaction with aldehydes, whereby polymerization of collagen molecules into fibrils is inhibited. Unwanted effects are cutaneous damage (diminished resistance to mechanical stress with a tendency to form blisters), nephrotoxicity, bone marrow depression, and taste disturbances. 

Occurrence of renal failure depends also on the patient s state of hydration, other treatments, and the rate of drug administration. Concomitant use of other nephrotoxic agents, pre-existing renal disease, and dehydration make further renal impairment with acyclovir more likely. 

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