Diabetes mellitus degenerates cisplatin-induced nephrotoxicity in short hydration method: a propensity score-matching analysis

Abstract

Cisplatin (CDDP)-induced nephrotoxicity (CIN) is dose-limiting. We revealed that co-administration of non-steroid anti-inflammatory drugs and baseline comorbidity of diabetes mellitus (DM) are associated with CIN development in the short hydration method; however, the results were accessorily obtained without appropriate power calculation. This study aimed to demonstrate the influence of DM complications on CIN incidence in a real-world setting. Lung cancer patients receiving CDDP (≥ 75 mg/m2)-containing regimens with a short hydration method (n = 227) were retrospectively evaluated. The patients were divided into control and baseline DM complication groups. The primary endpoint was the evaluation of CIN incidence between the groups. Propensity score-matching was performed to confirm the robustness of the primary analysis results. CIN occurred in 6.8% of control and 27.0% of DM patients, respectively, with a significant difference in all-patient populations (P = 0.001). In addition, variation of serum creatinine and creatinine clearance significantly worsened in DM patients. Similar results were obtained in a propensity-matched population. Multivariate logistic regression analysis found that DM complication is a singular risk factor for CIN development (adjusted odds ratio; 4.31, 95% confidence interval; 1.62–11.50, P = 0.003). In conclusion, our study revealed that baseline DM complications significantly worsen CIN.

Risk factor analysis for cisplatin-induced nephrotoxicity with the short hydration method in diabetic patients

“…We previously reported that patients with DM develop CIN at a significantly higher rate in a short hydration method 4 . Autophagy reportedly protects against CIN 8 , 13 , 14 , and its induction at the proximal tubule, where CIN mostly appears, is significantly suppressed in type 2 DM, which all participants met in previous and present studies 4 , 15 . Thus, we consider that the main mechanism of CIN degradation in type 2 DM is the reduction in renal autophagy.…”

“…Cisplatin (CDDP) is a key chemotherapeutic agent used to treat lung, head and neck, ovarian, esophageal, and urological malignancies 2 . Cisplatin-induced nephrotoxicity (CIN) is known to be its dose-limiting toxicity 2 , and reportedly occurs in 5–40% of the patients 2 – 4 . It is usually reversible, but becomes unreversible in cases of severe symptoms, and symptomatic treatment is limited 2 – 4 .…”

“…Cisplatin-induced nephrotoxicity (CIN) is known to be its dose-limiting toxicity 2 , and reportedly occurs in 5–40% of the patients 2 – 4 . It is usually reversible, but becomes unreversible in cases of severe symptoms, and symptomatic treatment is limited 2 – 4 . Oxidative stress, DNA damage, mitochondrial dysfunction, inhibition of protein synthesis, involvement of the tumor necrosis factor family, and decreased autophagy are all associated with CIN development 3 – 8 .…”

“…Magnesium supplementation, quality antiemetic therapy, and appropriate diuretic and hydration administration are the most important CIN prophylaxes and contribute to the reduction of CIN development to 0–10% 3 , 4 . Many reports evaluated CIN risk factors; however, most of the reports were not performed following the most recent CDDP administration methods with sufficient CIN prophylaxis described above 4 .…”

“…Magnesium supplementation, quality antiemetic therapy, and appropriate diuretic and hydration administration are the most important CIN prophylaxes and contribute to the reduction of CIN development to 0–10% 3 , 4 . Many reports evaluated CIN risk factors; however, most of the reports were not performed following the most recent CDDP administration methods with sufficient CIN prophylaxis described above 4 . It has been reported that the co-administration of non-steroidal anti-inflammatory drugs (NSAIDs) and baseline comorbidities of diabetes mellitus (DM) are risk factors for CIN development in the short hydration method, which is the most advanced method for CDDP administration 3 .…”