Drug-induced nephrotoxicity

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... 

Renal cell lines have been utilized to a limited extent for evaluation nephrotoxins. A rabbit kidney cell line (LLC-RKi) has been utilized for evaluating nephrotoxic antibiotics (Viano et al., 1983 Hottendorf et al., 1987 Williams et al., 1988). LLC-PKi cells have by far been the most widely employed cell line for studying drug-induced nephrotoxicity, specifically in the evaluation of aminoglycoside antibiotics (Hori et al., 1984 Schwertz et al., 1986 Williams et al., 1986b Holohan et al.,... 

Williams, P.D. (1989). The application of renal cells in culture in studying drug-induced nephrotoxicity. In Vitro 25 800-805. 

Superinfection, drug-induced lupus erythematosus, and Stevens-Johnson syndrome occur rarely nephrotoxicity with high dermatologic concentrations. 

Toxicities are numerous and include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hyperkalemia, altered mental status, seizures, and hirsutism. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) have been observed in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because the drug induces TGF-B, which promotes tumor invasion and metastasis. 

Porter, G. A., and Bennett, W. M. 1989. Drug-induced renal effects of cyclosporine, aminoglycoside antibiotics and lithium Extrapolation of animal data to man. In Nephrotoxicity Extrapolation from in vitro to in vivo, and animals to man, ed. Bach, P. H. and Lock, E. A., 147-170. New York, London Plenum Press. 

Thatte L, Vaamonde CA. Drug-induced nephrotoxicity the crucial role of risk factors. Postgrad Med 1996 100(6) 83, 87-8, 91 passim. 

Two patients with long-standing ulcerative colitis developed what seemed to be a drug-induced chronic interstitial nephritis after taking sulfasalazine for several years, with no other detectable cause (73) the same problem has arisen with mesalazine. However, in a long-term stndy (mean treatment time 10 years) in 36 patients taking sulfasalazine for ulcerative cohtis, there was no nephrotoxicity (74). 

There are several susceptibility factors for the development of contrast agent-induced renal damage, including pre-existing renal insufficiency, particularly if it is secondary to diabetes melhtus, dehydration, multiple repeat exposure to contrast media within a short period of time (72 hours), congestive heart failure, or concurrent administration of nephrotoxic drugs, such as non-steroidal antiinflammatory drugs (171). 

Metoclopramide reduces renal plasma flow, suggesting that concurrent use could increase the nephrotoxicity of cisplatin (21), an important observation in view of the specific usefulness of metoclopramide to treat cytotoxic drug-induced emesis. 

Table 4. Risk factors for drug-induced nephrotoxicity in the eideriy.

Choudhury D, Ahmed Z. Drug-induced nephrotoxicity. Med Clin N Am 1997 81 705-717. 

In general, drug-induced nephrotoxicity is reversible but given the high morbidity and mortality associated with AKI and the frequent and necessary use of drugs in critically iU patients clinicians should be aware of the potential nephrotoxicities and mechanisms. Thus this review will discuss mechanisms of drug-induced AKI and preventive strategies. We wiU discuss broadly... 

Perazella MA. 2003. Drug-induced renal failure update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sd 325 349-362. 

Izzedine FI, Launay-Vache,V, and Deray G. 2005. Antiviral drug-induced nephrotoxicity.Am7K/dneyD/s45 804-817. 

Williams PD. The application of renal cells In culture In studying drug-induced nephrotoxicity. In vitro 1989 25 800-805. Williams PD, Rush GF. An evaluation of in vitro models for assessing nephrotoxicity. in /n Wfrotoxicitytesting. Frazier JM (editor). Marcel Dekker Inc, NewYork/Basel/Flong Kong 1992 p. 85-110. 

Table 1. Cases of drug-induced nephrotoxicity and their pharmacovigilance commonalities...

Xiaoqing G, Chike N. Howto prevent, recognize, and threat drug-induced nephrotoxicity. Cleveland Clin J Med 2002 69 289-12. 

From an epidemiological point of view, among the causes of AKI of a medical nature, drug-induced and toxic AKI are very important [77]. Nephrotoxic substances include a wide variety of compounds such as heavy metal ions, organic solvents, antibodies and natural toxins. Nephrotoxins induce AKI in humans by direct cellular toxicity, vasoconstriction, and crystal-mediated tubular obstruction. Acute interstitial inflammation is an important factor in pathogenesis of acute interstitial nephritis. In general, a decrement of... 

Bertelli A,Giovannini L, Palla R, Migliori M, PanichiV, Andreini B Protective effect ofL-propionylcarnitine on cyclosporine-induced nephrotoxicity. Drugs Exp Clin Res 21 221 -8,1995... 

Izzedine H, Launay-VacherV, and Deray G. Antiviral drug-induced nephrotoxicity. American Journal of Kidney Diseases 45 804-817,2005. 

Guo X, Nzerue C, Howto prevent, recognize and treat drug-induced nephrotoxicity, Clev Clin J Med, 2002,69(4) 289-312. 

Beta-lactam induced renal toxicity can results from their use in monotherapy or when used in combination with other nephrotoxic drugs such as aminoglycosides, amphotericin B, cisplatin, cyclosporine, furosemide, ifosfamide, vancomycin and nephrotoxic p-lactams. While the risk of nephrotoxic injury from monotherapy with p-lactams is relatively low, this risk is substantially increased when multiple drug combinations are required. 

Coca S, Perazella MA. Acute renal failure associated with tenofovir evidence of drug-induced nephrotoxicity. Am J Med Sci 2002 324 342-344. 

IL-2 has been used in the treatment of sohd tumors such as metastatic melanoma, metastatic renal cell carcinoma, and colorectal carcinoma. Interleukin-2 infusions are associated with significant dose-dependent toxicity characterized by fevers, malaise, nausea, vomiting, diarrhea, hepatic dysfunction, pulmonary edema, somnolence, confusion, dysrhythmias, myocardial infarction, hematopoietic suppression, and renal insufficiency [10]. IL-2 has a short serum half-life of 6-10 min and a clearance of 30-60 min after bolus intravenously infusion [11]. Resultant toxicity is generally transient and reversible. It is possible that IL-2 induced renal failure only occurs in the setting of profound hypotension, prior volume depletion, concurrent administration of potentially nephrotoxic drugs, or the presence of underlying renal disease. 

There are numerous methods to determine the nephrotoxic potential of a chemical or to study the mechanism(s) by which a chemical induces nephrotoxicity. In humans, the concern is most often related to either drug-induced or occupationally associated nephrotoxicity. Evaluation of nephrotoxicity in humans is limited primarily to the measurement of urinary changes (e.g., volume, enzymes, protein, etc.), BUN or serum creatinine concentrations, creatinine clearance, or renal biopsy. The measurement of an increase in urinary N-acetyl-jS-D-glucosaminidase (NAG) or alanine aminopeptidase (AAP) levels,... 

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