An 84-year-old man is brought to the physician by the staff of a group home where he resides because of worsening confusion and decreased urinary output. His nurse reports that the patient has not been drinking much for the last 3 days. Examination shows a decreased skin turgor and dry oral mucosa. His pulse is 105/min and blood pressure is 100/65 mm Hg. His serum creatinine is 3.1 mg/dL and a urea nitrogen is 42 mg/dL. Urine studies show multiple brownish granular casts. Which of the following processes is most likely involved in the pathogenesis of this patient's condition?

Necrosis of tubular epithelial cells

Immune complex deposition in mesangium

Leukocytic infiltration of renal interstitium

Disruption of glomerular podocytes

A 57-year-old man comes to the emergency department because of pain in the sides of his abdomen and blood-tinged urine since the previous night. Over the last 2 days, he has also had progressive malaise, myalgia, and a generalized itchy rash. He has a history of gastroesophageal reflux that did not respond to ranitidine but has improved since taking pantoprazole 2 months ago. He occasionally takes acetaminophen for back pain. His vital signs are within normal limits. Examination shows a generalized, diffuse maculopapular rash. The remainder of the examination shows no abnormalities. Laboratory studies show: Hemoglobin 13 g/dL Leukocyte count 7,800/mm3 Serum Na+ 140 mEq/L Cl- 105 mEq/L K+ 4.6 mEq/L HCO3- 25 mEq/L Glucose 102 mg/dL Creatinine 4.1 mg/dL Renal ultrasonography shows no abnormalities. Which of the following findings is most likely to be observed in this patient?

Elevated levels of eosinophils in urine

Mesangial IgA deposits on renal biopsy

Urinary crystals on brightfield microscopy

Crescent-shape extracapillary cell proliferation

Papillary calcifications on CT imaging

A hospitalized 45-year-old man has had mild flank pain since awakening 3 hours ago. He also reports a new generalized rash. Two weeks ago, he was diagnosed with pulmonary tuberculosis. Current medications include isoniazid, pyrazinamide, rifampin, ethambutol, and pyridoxine. His temperature is 38.3°C (100.9°F), pulse is 74/min, and blood pressure is 128/72 mm Hg. Examination of the skin shows diffuse erythema with confluent papules. There is no costovertebral angle tenderness. Laboratory studies show: Leukocyte count 9,800/mm3 Segmented neutrophils 59% Bands 3% Eosinophils 4% Lymphocytes 29% Monocytes 5% Serum Urea nitrogen 25 mg/dL Creatinine 1.9 mg/dL Urine WBC 8–10/hpf Eosinophils numerous RBC 5–6/hpf RBC casts negative WBC casts numerous In addition to intravenous fluid resuscitation, which of the following is the most appropriate next step in management?

Perform serum protein electrophoresis

Drug-induced kidney injury for USMLE Step 1: High-Yield Pharmacology Lessons

Mechanisms of Injury - How Drugs Wreck Kidneys

Nephron sites of drug-induced kidney injury

Hemodynamic-Mediated: Drugs alter renal blood flow.
- NSAIDs, calcineurin inhibitors → Afferent arteriole vasoconstriction (↓ GFR).
- ACE inhibitors, ARBs → Efferent arteriole vasodilation (↓ GFR).
Acute Tubular Necrosis (ATN): Direct toxicity to tubular cells.
- Aminoglycosides, cisplatin, amphotericin B, IV contrast.
Acute Interstitial Nephritis (AIN): Allergic, inflammatory infiltrate.
- Penicillins, PPIs, sulfa drugs, NSAIDs.
Crystal Nephropathy: Drug precipitation obstructs tubules.
- Acyclovir, sulfonamides, methotrexate.

⭐ Exam Favorite: The classic triad of fever, rash, and arthralgia for Acute Interstitial Nephritis (AIN) is present in only 5-10% of cases. Eosinophiluria is a more suggestive finding.

Causative Agents - The Usual Suspects

Mechanism of Injury	Causative Agents
Acute Tubular Necrosis (ATN)	* Aminoglycosides (e.g., Gentamicin) - most common cause

Radiocontrast media
Cisplatin
Amphotericin B
Foscarnet | | Acute Interstitial Nephritis (AIN) | * 📌 The 5 P's: Pee (Diuretics), Pain-free (NSAIDs), Penicillins & cephalosporins, Proton pump inhibitors, rifamPin.
Allopurinol, Sulfa drugs | | Hemodynamic Injury | * Prerenal Azotemia (Afferent Arteriole Constriction): NSAIDs, Cyclosporine
Efferent Arteriole Dilation: ACE inhibitors, ARBs | | Crystal Nephropathy | * Acyclovir (especially IV)
Sulfonamides
Methotrexate
Indinavir
Triamterene | | Thrombotic Microangiopathy | * Cyclosporine
Quinine
Antiplatelet agents (Ticlopidine, Clopidogrel) |

⭐ NSAIDs are notorious for causing kidney injury through multiple mechanisms, including acute interstitial nephritis (AIN), hemodynamically-mediated injury (by constricting the afferent arteriole), and can also lead to papillary necrosis.

Clinical Picture & Diagnosis - Spotting the Damage

Presentation: Often asymptomatic initially. Can present with non-specific uremic symptoms (fatigue, nausea) or oliguria/anuria.
Core Labs:
- ↑ Serum Creatinine (SCr) & BUN. AKI criteria:
  - ↑ SCr by ≥0.3 mg/dL within 48 hours, OR
  - ↑ SCr to ≥1.5x baseline within 7 days, OR
  - Urine volume <0.5 mL/kg/h for 6 hours.
- Urinalysis: Key to pinpointing the lesion type.
  - ATN: Muddy brown granular casts.
  - AIN: WBC casts, eosinophiluria.
  - Glomerulonephritis: RBC casts, proteinuria.
Imaging: Renal ultrasound helps rule out obstruction.

⭐ Eosinophiluria is a classic finding for drug-induced Acute Interstitial Nephritis (AIN), but it is neither sensitive nor specific.

Urinary sediment: ATN muddy brown casts vs AIN WBC casts

Management & Prevention - Damage Control

Primary goal: Discontinue the nephrotoxic drug immediately.
Supportive care: Ensure euvolemia, typically with isotonic IV fluids.
Avoid other potential nephrotoxins (e.g., NSAIDs, IV contrast).
Adjust dosages for all renally excreted medications.

⭐ To prevent contrast-induced nephropathy, the most proven intervention is pre-procedure IV hydration with isotonic saline. N-acetylcysteine use is controversial but sometimes considered.

High‑Yield Points - ⚡ Biggest Takeaways

Acute Tubular Necrosis (ATN) is the most common form of drug-induced kidney injury, classically caused by aminoglycosides, radiocontrast media, and cisplatin.

Hemodynamically-mediated injury is often due to NSAIDs (afferent constriction) and ACE inhibitors (efferent dilation).

Acute Interstitial Nephritis (AIN) is a hypersensitivity reaction, commonly linked to penicillins, NSAIDs, and PPIs.

Crystal nephropathy can be induced by acyclovir, sulfonamides, and methotrexate.

Chronic Interstitial Nephritis is a key adverse effect of long-term lithium use.

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