144 PART THREE | DELIRIUM This final chapter summarizes the findings and main conclusions of the reported clinical studies on key topics in palliative and supportive care for patients with advanced cancer, including cisplatin-induced acute kidney injury, chemotherapy-induced nausea and vomiting, and delirium, followed by an in-depth interpretation, analysis and synthesis of the findings. In addition, recommendations are provided for clinical practice and future research. Part One: Cisplatin-induced acute kidney injury In Chapter 2 we report the incidence and risk factors of acute kidney injury (AKI) in patients treated with concurrent chemoradiotherapy (CRT) including 3-weekly high-dose (100 mg/m2) cisplatin for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). The incidence of AKI was 69%; the majority of AKI cases according to the Kidney Disease Improving Global Outcomes (KDIGO) classification were stage 1 (83%), with a smaller fraction of stages 2 (12%) and 3 (5%). Risk factors were hypertension (Odds Ratio [OR] 2.7, 95% Confidence Interval [CI] 1.1-6.6; p = 0.03) and chemotherapy-induced nausea and vomiting (CINV; OR 4.3, 95% CI 1.6-11.3; p = 0.003). The incidence of AKI in hospitalized individuals varies substantially with the population evaluated and the definitions used [1]. The lack of standard definition of the syndrome has a great impact in the reported incidence and clinical significance of AKI. In previous studies involving patient populations with LA-SCCHN treated with high-dose cisplatin concurrent with radiotherapy, emphasis was given to the most severe acute reduction in kidney function, previously called acute renal failure (ARF), as manifested by severe azotaemia and often by oliguria or anuria. In these studies, acute nephrotoxicity was commonly graded by an increase in serumcreatinine (SCr) levels according to the Common Terminology Criteria for Adverse Events (CTCAE). Using these criteria, nephrotoxicity ≥grade 3 occured in only 4-8% of patients [2-5]. Latcha et al [6], defining AKI as an increase from baseline SCr of >25% within 30 days after the first cycle of cisplatin, retrospectively analysed data from 821 patients treated with cisplatin for multiple tumor types. They found that AKI occured in 31.5% of cases. Evidence suggests that even relatively mild injury or impairment of kidney function manifested by small changes in SCr and / or urine output, is a predictor of serious clinical consequences [7-10]. For this reason, AKI has replaced the term ARF. The concept of AKI, as defined by RIFLE (an acronym of the Risk-Injury-Failure; Loss, End-stage renal disease) [11], encompasses acute tubular necrosis and ARF as well as other, less severe conditions. It includes patients without actual damage to the kidney but with functional impairment (low stage AKI). Including such patients in the classification of AKI is clinically important, because they may benefit most from early intervention. According to the RIFLE criteria three severity grades are defined (Risk, Injury and Failure) and two outcome classes (Loss and End-stage renal disease). The severity criteria of AKI are defined on the basis of the changes in SCr or urine output where the worst of each criterion is used. The outcome criteria are defined by the duration of impairment of kidney function In a retrospective study, Espeli et al [12] used the RIFLE criteria to define renal damage in 94 patients with
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