A 62-year-old male in the intensive care unit is being treated for severe sepsis with norepinephrine and was started on piperacillin/tazobactam 3 days ago. He now develops acute kidney injury characterized by a rising serum creatinine and decreased urine output. Additionally, he has fever, a diffuse maculopapular rash, and laboratory tests reveal eosinophilia (15%) and an elevated white blood cell count. Considering his clinical presentation and recent medication history, which of the following is the MOST likely mechanism of his acute kidney injury?

A 72-year-old man with type 2 diabetes mellitus, chronic kidney disease (CKD) Stage 3 (baseline serum creatinine 1.8 mg/dL), and hypertension is admitted to the ICU for severe community-acquired pneumonia. He is on mechanical ventilation in assist-control mode with a tidal volume of 6 mL/kg predicted body weight and PEEP of 8 cm H₂O. He requires a continuous norepinephrine infusion via a central line, started at 0.04 mcg/kg/min and increased to 0.10 mcg/kg/min to maintain a mean arterial pressure >65 mmHg. His net fluid balance over the past 24 hours is +1.2 L. On hospital day 3, his serum creatinine rises to 3.5 mg/dL, and urine output decreases to <0.3 mL/kg/h. Medications include intravenous vancomycin 15 mg/kg every 12 hours (no trough levels available) and ibuprofen 400 mg every 6 hours for pain control. Which of the following is the most significant contributor to this patient’s acute kidney injury?

A 24-year-old, 60 kg patient presents to the Emergency Department 4 hours after an intentional aspirin overdose. The patient is agitated with tinnitus and tachypnea. Vital signs are: BP 130/80 mmHg, HR 110/min, RR 30/min, SpO₂ 98% on room air. Initial arterial blood gas on room air shows pH 7.55, pCO₂ 22 mmHg, and HCO₃⁻ 18 mEq/L (mixed respiratory alkalosis and metabolic acidosis). A point-of-care salicylate level is 105 mg/dL (therapeutic 15–30 mg/dL). Urine output is 60 mL/hr (1 mL/kg/hr). Which of the following is the most appropriate next intervention?

An 82-year-old man with osteoarthritis has been taking ibuprofen 400 mg three times daily for several months. Recent labs show a serum creatinine of 1.8 mg/dL (baseline 0.9 mg/dL) and BUN of 35 mg/dL. Blood pressure is 118/72 mmHg. Considering age-related pharmacokinetic and pharmacodynamic changes, which of the following best explains his increased susceptibility to ibuprofen-induced acute kidney injury?

A 62-year-old man in the ICU with septic shock secondary to severe pneumonia is mechanically ventilated and receiving norepinephrine. He has been on vancomycin and piperacillin/tazobactam for 72 hours. His baseline serum creatinine was 0.9 mg/dL; it is now 2.1 mg/dL. Urine output over the past 24 hours is 300 mL. Laboratory studies show serum potassium 5.8 mEq/L. Urinalysis reveals muddy brown granular casts, urine sodium 68 mEq/L, and a fractional excretion of sodium (FENa) of 2.4%. Which of the following findings MOST strongly supports intrinsic, drug-induced acute tubular injury in this patient?

A 65-year-old man with a history of hypertension and sepsis due to Pseudomonas aeruginosa was treated with piperacillin/tazobactam 4.5 g IV every 6 hours. On day 7 of therapy, his serum creatinine increased from 1.0 mg/dL to 2.4 mg/dL and BUN rose from 18 mg/dL to 30 mg/dL (BUN/Cr ratio ≈ 12.5). Over the past 24 hours he produced 800 mL of urine. Urinalysis shows 15–20 WBCs/HPF, occasional white cell casts, and no RBCs or granular casts. Renal ultrasound is unremarkable. Based on these findings, which of the following is the MOST likely pattern of drug-induced kidney injury?

A 62-year-old male (weight 80 kg) is admitted to the ICU with severe sepsis secondary to pneumonia. He is intubated, on norepinephrine at 0.1 mcg/kg/min (mean arterial pressure 70 mm Hg, heart rate 110 bpm), and has received 2 L of crystalloid over the past 24 hours (net positive balance +1.2 L). His baseline serum creatinine (SCr) 3 months ago was 0.9 mg/dL. He was 1.1 mg/dL on admission 48 hours ago. Over the last 24 hours, SCr rose to 2.8 mg/dL, and urine output has been 0.3 mL/kg/hr for 12 hours. Current antibiotics: vancomycin 15 mg/kg IV q12h (last dose 6 hours ago) and piperacillin/tazobactam 4.5 g IV q6h. He has hypertension and type 2 diabetes. Which of the following is the most appropriate immediate intervention?

A 58-year-old man with hypertension and type 2 diabetes is admitted for a severe bacterial infection requiring nephrotoxic antibiotics. His baseline kidney function is normal, but the clinical team is concerned about early detection of drug-induced kidney injury (DIKI). They inquire about the utility of emerging biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) for early diagnosis and prognosis. Based on current clinical guidelines, which statement best describes the role of these biomarkers in managing DIKI?

A 65-year-old male in the ICU with septic shock secondary to pneumonia has been hemodynamically stabilized on norepinephrine at 0.1 mcg/kg/min, maintaining a MAP of 65 mm Hg. He is clinically euvolemic with a net even fluid balance over the past 6 hours. His urine output has fallen to 15 mL over the last 2 hours. Laboratory studies show serum creatinine rising from a baseline of 0.9 mg/dL to 2.5 mg/dL, BUN 45 mg/dL, sodium 140 mEq/L, potassium 4.2 mEq/L, and a fractional excretion of sodium of 2.1%. He has been on empiric vancomycin for 5 days. The most recent vancomycin trough is 35 mcg/mL, and a 24-hour AUC is estimated at 700 mg·h/L. Considering his clinical presentation and medication profile, what is the MOST appropriate initial management step for his acute kidney injury?

A 62-year-old, 70 kg male in the ICU with severe sepsis due to Pseudomonas aeruginosa (meropenem MIC 2 mg/L) and acute kidney injury is receiving continuous venovenous hemodiafiltration (CVVHDF) with an effluent flow rate of 25 mL/kg/h. Which meropenem dosing regimen is most likely to achieve the pharmacodynamic target of free drug concentration above the MIC for ≥40% of the dosing interval while minimizing toxicity?