Cisplatin nephrotoxicity aggravated by cardiovascular disease and diabetes in lung cancer patients

Abstract

Ageing lung cancer patients may be at increased risk of Cisplatin (Cp) nephrotoxicity, because of comorbidities leading to accelerated ageing of the kidneys. Therefore, the Cp-induced impairement of renal function was compared between no comorbidity (NC) and hypertension plus ischaemic heart disease (CD) patients or others having diabetes mellitus plus ischaemic heart disease (DMIH).In a preliminary study, glomerular filtration rate (GFR) was measured by clearance of technetium 99m-labelled diethylene-thiamine penta-acetate in 38 lung cancer patients with normal serum creatinine concentration ([creat]). Then, the incidence of nephrotoxicity was analysed retrospectively over 1st-4th cycles of Cp treatment among 242 lung cancer patients with initially normal [creat]. GFR was repeatedly estimated using calculated creatinine clearance.Pre-treatment GFR was 57¡3 mL?min -1 ?m -2 in those with normal (n515) and 42¡2 mL?min (n552) subgroups. Within the overall dropout rate from further Cp chemotherapy, nephrotoxicity was responsible in 14% of NC, 38% in CD and 75% in DMIH patients. A major portion of our ageing lung cancer patients suffered from comorbidities leading to reduced renal resistance to Cp nephrotoxicity.

Incidence of Cisplatin-Induced Nephrotoxicity and Associated Factors among Cancer Patients in Indonesia

“…Mathe et al (2011) and Lavole et al (2012) reported that cardiovascular diseases (hypertension and ischemic heart disease) and diabetes mellitus increase the risk of nephrotoxicity in lung cancer patients. In this study, diabetes mellitus did not influence the occurrence of nephrotoxicity.…”

“…In general, old age is one of many factors that increase the risk of drug nephrotoxicity (Perazella, 2009). Some studies showed that older age is a risk factor for the development of cisplatin nephrotoxicity due to reduced number and volume of tubules, as well as increased synthesis of reactive oxygen compounds and inflammation in the ageing kidney (Caglar et al, 2002;de Jongh et al, 2003;Mathe et al, 2011;BC Cancer Agency, 2013). Geriatric patients tend to have chronic kidney disease despite having no comorbidities (Stevens et al, 2010) and the prevalence of renal impairment is high in elderly cancer patients (Thomas and Thomas, 2009;Aapro and Launay-Vacher, 2012).…”

“…However, cisplatin has severe side effects such as bone marrow suppression, gastrointestinal toxicity, ototoxicity, neuropathy and nephrotoxicity. Of these, nephrotoxicity is the major side effect that may restrict the therapeutic use of cisplatin (Tiseo et al, 2007;Pabla and Dong, 2008;Mathe et al, 2011). The most severe nephrotoxicity of cisplatin is acute kidney injury, occurring in 20-30% patients treated with the drug (Miller et al, 2010).…”

Protective effect of CV247 against cisplatin nephrotoxicity in rats

“…High-dose cisplatin-induced nephrotoxicity (>25% decrease in eGFR) was diagnosed in 29 % of patients, following a single dose of cisplatin, and temporary elevation of serum creatinine concentration above the upper normal limit was observed in 41% of 400 cisplatin-treated patients with different solid tumours. 17 Comorbidities in lung cancer patients greatly increased the incidence of cisplatin-induced nephrotoxicity from 7.5% without co-morbidities to 20.9% with concurrent hypertension with or without ischemic heart disease, and to 30.8% with diabetes mellitus and ischaemic heart disease 18 . Due to the superior efficacy of cisplatin against a variety of human carcinomas, intensive efforts have been undertaken to weaken the side effects especially the nephrotoxic effect of cisplatin.…”

Estimating glomerular filtration rate in oncology patients receiving Cisplatin chemotherapy: Predicted creatinine clearance against 99mTc-DTPA methods

“…Increasing age physiologically will lead to reducing GFR level [8]. Since cancer risk is also increasing with increasing age, therefore renal resistance towards cisplatin will also be reduced as age increases [9].…”