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 (n = 15) and 42 ± 2 mL·min⁻¹·m⁻² in those with pathologically increased (n = 23) [creat] any time following their 2nd-4th Cp cycle (p < 0.05). The retrospective analysis revealed that Cp-induced nephrotoxicity developed in 7.5% of the NC (n = 80), in 20.9% of the CD (n = 110) and in 30.8% of the DMIH (n = 52) 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.