No abstract

Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium thiosulfate and diethyldithiocarbamate. Dose- and age-related proximal tubular damage is an adverse effect of ifosfamide. In addition to renal wasting of electrolytes, glucose and amino acids, Fanconi syndrome, rickets and osteomalacia have occurred with ifosfamide treatment. High dose azacitidine causes renal dysfunction manifested by tubular acidosis, polyuria and increased urinary excretion of electrolytes, glucose and amino acids. Haemolytic uraemia is a rare adverse effect of gemcitabine. Methotrexate can cause increased serum creatinine levels, uraemia and haematuria. Acute renal failure is reported following administration of high dose methotrexate. Urinary alkalisation and hydration confer protection against methotrexate-induced renal dysfunction. Dose-related nephrotoxicity, including acute renal failure, are reported subsequent to treatment with pentostatin and diaziquone. Acute renal failure is a rare adverse effect of treatment with interferon-alpha. Haemolytic uraemic syndrome occurs with mitomycin administration. A mortality rate of 50 to 1...

Prostate cancer is the leading cancer diagnosis and second leading cause of cancer-related mortality for men in the United States. Due to the increased prevalence of prostate cancer in men older than 50 years, men at risk for prostate cancer represent the same population of men who are at greatest risk for metabolic syndrome, diabetes mellitus, and coronary artery disease (CAD). In addition to risk factors for CAD that are applicable to the general population, men with prostate cancer can be at increased risk for CAD due to long-term androgen deprivation therapy (ADT) administered as treatment for prostate cancer. Men undergo ADT by medical (drug therapy) or surgical (castration) means. Luteinizing hormone-releasing hormone (LHRH) agonists are the primary drug therapies used for ADT. Commercially available LHRH agonists are goserelin, histrelin, leuprolide, and triptorelin. Body composition changes, hyperlipidemia, insulin resistance, metabolic syndrome, and acute coronary syndrome are all reported adverse effects of ADT, which are consequences of reduced levels of circulating testosterone. Metabolic and body composition changes associated with ADT arise within months of beginning medical ADT and persist after discontinuation of therapy. To better understand the increased risk of metabolic syndrome, diabetes, and heart disease in patients undergoing ADT for prostate cancer, we performed a MEDLINE search (1986-2008) to identify pertinent studies and reports. Additional citations were obtained from the articles retrieved from the literature search. We found that the increased risk for serious cardiovascular disease becomes evident within months of beginning ADT. Pharmacists should provide counseling to these patients on primary disease prevention. Men receiving ADT should be monitored routinely for signs and symptoms of metabolic syndrome, diabetes, and CAD. Healthy lifestyle practices should be encouraged, and physical therapy should be considered for these patients.