Drug-induced impairment of renal function

George Sunny Pazhayattil, Anushree C Shirali Section of Nephrology, Yale University School of Medicine, New Haven, CT, USA Abstract: Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies. Keywords: acute kidney injury, chronic kidney disease, drug nephrotoxicity, chemotherapy, NSAID

Peripheral markers (Clara cell protein and alpha-glutathione S-transferase) and lipidoperoxidation (malondialdehyde) assessment in Sprague-Dawley rats instilled with haematite and benzo[a]pyrene

The literature suggests that the concomitant exposure to polycyclic aromatic hydrocarbons (PAH) and ferric oxide particles could enhance lung cancer incidence in environmental and occupational settings, High levels of tracheobronchial tumours were obtained in hamsters exposed to benzo[a]pyrene (B[a]P) adsorbed onto ferric oxide carrier particles, Therefore, we have assessed the toxic effects of exposure to haematite (Fe2O3) and B[a]P in male Sprague-Dawley rats, Animals were instilled with the chemicals alone (3 mg of Fe2O3 or B[a]P) or in combination (3 mg Fe2O3 + 3 mg B[a]P), Bronchoalveolar lavages (BAL) and biological samples (serum and urine) were collected 48 h after the intoxication, Clara cell protein (CC16) and alpha-glutathione S-transferase (alpha-GST), as peripheral markers of both tracheobronchial epithelial cell integrity and renal dysfunction, were determined in BAL fluid, serum and urine, Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in BAL fluid and serum, We observed a significant increase of CC16 concentrations in BAL fluid after Fe2O3+B[a]P instillation (p<0.05) in serum after Fe2O3 and Fe2O3+B[a]P exposure (p<0.01) and in urine after B[a]P administration (p<0.01). Instillation of Fe2O3 + B[a]P produced an increased amount of alpha-GST in BAL fluid (p<0.01), whereas B[a]P alone caused a significant elevation of or-GST in serum and urine (p<0.01), Moreover, Fe2O3 or Fe2O3 + B[a]P instillation induced a significant increase in MDA levels in BAL fluid (p<0.01 and p<0.05), In conclusion, Fe2O3 may have a low pulmonary toxicity. However, B[a]P manifested a rapid and high toxicity in the respiratory tract and kidneys, When B[a]P was adsorbed on haematite particles, both its retention in the respiratory tract and pulmonary toxicity increased. (C) 1998 John Wiley & Sons, Ltd