Daily Caffeine Consumption May Increase the Risk of Acute Kidney Injury Related to Platinum-Salt Chemotherapy in Thoracic Cancer Patients: A Translational Study.
Aghilès HamrounAntoine DecaesteckerRomain LarrueSandy FellahDavid BlumCynthia Van der HauwaertArnaud ScherpereelAlexis CortotRémi LenainMehdi MaanaouiNicolas PottierChristelle CauffiezFrançois GlowackiPublished in: Nutrients (2024)
Although their efficacy has been well-established in Oncology, the use of platinum salts remains limited due to the occurrence of acute kidney injury (AKI). Caffeine has been suggested as a potential pathophysiological actor of platinum-salt-induced AKI, through its hemodynamic effects. This work aims to study the association between caffeine consumption and the risk of platinum-salt-induced AKI, based on both clinical and experimental data. The clinical study involved a single-center prospective cohort study including all consecutive thoracic cancer patients receiving a first-line platinum-salt (cisplatin or carboplatin) chemotherapy between January 2017 and December 2018. The association between daily caffeine consumption (assessed by a validated auto-questionnaire) and the risk of platinum-salt induced AKI or death was estimated by cause-specific Cox proportional hazards models adjusted for several known confounders. Cellular viability, relative renal NGAL expression and/or BUN levels were assessed in models of renal tubular cells and mice co-exposed to cisplatin and increasing doses of caffeine. Overall, 108 patients were included (mean age 61.7 years, 65% men, 80% tobacco users), among whom 34 (31.5%) experienced a platinum-salt-induced AKI (67% Grade 1) over a 6-month median follow-up. The group of high-caffeine consumption (≥386 mg/day) had a two-fold higher hazard of AKI (adjusted HR [95% CI], 2.19 [1.05; 4.57]), without any significant association with mortality. These results are consistent with experimental data confirming enhanced cisplatin-related nephrotoxicity in the presence of increasing doses of caffeine, in both in vitro and in vivo models. Overall, this study suggests a potentially deleterious effect of high doses of daily caffeine consumption on the risk of platinum-salt-related AKI, in both clinical and experimental settings.
Keyphrases
- acute kidney injury
- cardiac surgery
- high glucose
- drug induced
- diabetic rats
- risk assessment
- spinal cord
- clinical trial
- endothelial cells
- cardiovascular disease
- newly diagnosed
- radiation therapy
- poor prognosis
- ejection fraction
- machine learning
- squamous cell carcinoma
- electronic health record
- palliative care
- prognostic factors
- spinal cord injury
- chronic kidney disease
- patient reported
- locally advanced
- cell death
- coronary artery disease
- patient reported outcomes
- binding protein
- phase ii study
- pi k akt
- childhood cancer