Evaluation of Prediabetes in Cisplatin-induced Nephrotoxicity in the Short Hydration Method: A Subgroup Analysis

Abstract

Background/Aim: Cisplatin-induced nephrotoxicity (CIN) is one of the most attention-requiring adverse effects. We have reported that diabetes mellitus significantly increases the incidence of CIN in a short hydration method in real-world lung cancer treatment. However, the effect of prediabetes on CIN development remains unclear. This study investigated whether patients with prediabetes exhibit CIN at a greater rate during real-world cisplatin-including treatments as a subgroup analysis. Patients and Methods: This retrospective observational study enrolled patients with lung cancer receiving cisplatin treatment (≥75 mg/m 2 ) from May 2014 to January 2021 (n=169). Patients were divided into a prediabetes group (baseline HbA1c 5.7-6.4%) and a control group (baseline HbA1c <5.7%). The primary endpoint of this study was the incidence of CIN in all treatment cycles between the two groups. We also assessed variations in serum creatinine (SCr) levels and creatinine clearance (CCr). Results: CIN occurred in 4.7% of controls and 8.3% of patients with prediabetes in all cycles, with no significant difference (p=0.37). In contrast, variation of SCr levels and CCr was significantly worse in the prediabetes group [median variation level (range) 0.11 mg/dl (-0.11-0.46 mg/dl) and 0.12 mg/dl (-0.02-1.08 mg/d) in controls and prediabetes, p=0.04 for SCr; -12.9 ml/min (-54.1-4.9 ml/min) and -16.3 ml/min (-49.4-3.0 ml/min), p=0.02 for CCr, respectively]. These results were also confirmed during the first cycle of treatment. Conclusion: Patients with prediabetes did not develop problematic CIN, although they exhibited significant increases in SCr and decreases in CCr.Cisplatin is a cytotoxic chemotherapeutic agent used in treating lung, ovarian, head and neck, urological, and esophageal malignancies (1-3). However, it has potent adverse effects, including gastrointestinal symptoms, neurotoxicity, ototoxicity, and nephrotoxicity (3). Cisplatininduced nephrotoxicity (CIN) is one of the most important adverse effects of cisplatin treatment and affects ongoing and future treatment strategies. Because cisplatin is administered in a variety of treatment settings, including metastasis, perioperative treatment, and chemoradiotherapy, its management is important for effective and less onerous treatment. CIN is dose-dependent, cumulative, usually reversible (2, 3), and is the dose-limiting toxicity of cisplatin (3-5). CIN used to occur in 30-40% of patients (3). However, supportive care, including magnesium and appropriate diuretic administration with quality antiemetic treatment, has decreased its incidence to 0-10% (6).Many studies have evaluated the factors associated with CIN incidence, although cisplatin administration methods vary 800