Anticancer Drug???Induced Kidney Disorders

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...

Management of Treatment-Related Toxicity in Advanced Ovarian Cancer

“…Gemcitabineinduced alopecia is rarely worse than grade 2, and no cumulative hepatic or direct renal toxicities have been reported for gemcitabine [51]. However, the development of thrombotic microangiopathy may result after extended use of gemcitabine [41], and potentially life-threatening hemolytic uremia can occur secondary to this effect [52,53].…”

Cisplatin Binding and Inactivation of Mitochondrial Glutamate Oxaloacetate Transaminase in Cisplatin-Induced Rat Nephrotoxicity

“…10) Patients treated with cisplatin commonly show a glomerular filtration rate 20-40% lower than people without treatment. 11) Other clinical data have also shown that approximately one third of patients develop renal injury in the days following cisplatin treatment, with reduced glomerular filtration rates, increased blood urea nitrogen and serum creatinine, and imbalanced electrolytes. 12,13) In cisplatin nephrotoxicity, the key pathological features are renal tubular cell injury and death.…”

Microalbuminuria Is Not Associated with Cisplatin‐Induced Azotemia in Dogs

“…11 Optimally, a through assessment of kidney function, including evaluating glomerular filtration, as well as proximal tubule and distal tubule function is recommended in people treated with cisplatin. 12 Glomerular filtration rate can be evaluated with inulin, creatinine, iohexol, and radioisotopes such as 99m Tc diethylenetriamine pentaacetic acid plasma clearance. 4 Proximal tubule function is assessed by measuring fractional excretion of glucose, uric acid, calcium, phosphorus, and magnesium as well as determining the renal threshold for phosphate, bicarbonate, and low molecular protein excretion.…”

“…4 Proximal tubule function is assessed by measuring fractional excretion of glucose, uric acid, calcium, phosphorus, and magnesium as well as determining the renal threshold for phosphate, bicarbonate, and low molecular protein excretion. 12 Urine osmolality and pH evaluate distal tubule function. 12 Measuring urine protein and enzyme excretion and evaluating urine sediment complete the urinalysis.…”

“…12 Urine osmolality and pH evaluate distal tubule function. 12 Measuring urine protein and enzyme excretion and evaluating urine sediment complete the urinalysis. 12 In clinical practice in human medicine, the measurement of serum creatinine, blood urea nitrogen (BUN), electrolyte concentrations, and creatinine clearance are commonly performed to evaluate renal function before each cisplatin treatment.…”