14 Several classification systems have been developed to streamline research and clinical practice with respect to AKI [34-36]. The 2011 Kidney Disease: Improving Global Outcomes (KDIGO) definition and staging criteria of AKI [36] are based on the Risk, Injury, Failure; Loss, End-stage renal disease (RIFLE) [34] and Acute Kidney Injury Network (AKIN) [35] classifications for AKI. According to KDIGO, AKI is diagnosed by an absolute increase in serum creatinine (SCr) at least 0.3 mg/dl (≥26.5 μmol/l ) within 48 hours (hr) or by a 50% increase in SCr from baseline within 7 days, or a urine volume of less than 0.5 ml/kg/h for at least 6 hr (Table 1). A patient’s progress can be staged over the entire time frame encompassed by an episode of AKI. An increase in SCr up to 3 times from baseline, or a SCr of more than 4.0 mg/dL (354 μmol/L), or initiation of renal replacement therapy (RRT), are all classified as stage 3. Table 1. Staging of AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification. Stage Serum Creatinine Urine output 1 1.5–1.9 times baseline OR ≥0.3 mg/dl (≥26.5 μmol/l) increase <0.5 ml/kg/h for 6-12 hr 2 2.0–2.9 times baseline <0.5 ml/kg/h for ≥12 hr 3 3.0 times baseline OR Increase in SCr to ≥4.0 mg/dl (≥353.6 μmol/l) OR Initiation of RRT OR In patients <18 years, decrease in GFR to <35 ml/min per 1.73 m2 <0.3 ml/kg/h for ≥24 hr OR Anuria for ≥12 hr Abbreviations: GFR, glomerular filtration rate; Hr, hours; RRT, renal replacement therapy; SCr, serum creatinine. In squamous cell carcinomas of the head and neck (SCCHN), the prevailing clinical presentation is a locoregionally advanced (LA) disease stage, for which patients are usually offered a multimodality approach involving chemoradiotherapy (CRT) [37, 38]. Based on four large randomized trials [39-42], conventionally fractionated external beam radiotherapy with concurrent administration of three cycles of high-dose cisplatin (100 mg/m2) given once every 3 weeks represents the current standard in definitive and adjuvant treatment of LASCCHN, as it results insignificantlybetter locoregional control and/oroverall survival relative to radiotherapy alone. Nevertheless, concerns exist about its toxicity and compliance, and AKI is considered a dose-limiting toxicity of cisplatin in this patient group [43]. Chapter 2 describes the results of a retrospective cohort study to establish the incidence and risk factors of AKI among patients diagnosed with LA-SCCHN who were treated with high-dose cisplatin-based CRT. In this chapter, we also investigate the impact of cisplatininduced AKI on long-term renal function and treatment outcomes in this patient cohort.
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