Pharmacotherapy Lecture on Acute Tubular Necrosis

Acute Tubular Necrosis (ATN)

• Acute Tubular Necrosis (ATN) is the primary cause of intrinsic acute kidney injury (AKI).
• ATN involves necrosis of tubular epithelial cells due to nephrotoxins (e.g., aminoglycosides, contrast media) and conditions like sepsis and ischaemia.
• Damage leads to tubular blockage by debris, increasing tubular pressure and hindering the elimination of sodium, water, and metabolic waste.
• If untreated, prerenal AKI may progress to ATN.

Postrenal Acute Kidney Injury

• Postrenal AKI results from obstruction of urinary outflow, affecting the ureters, urinary bladder, or urethra.
• Common causes include benign prostatic hyperplasia (BPH), pelvic tumors, and kidney stones (nephrolithiasis).

Clinical Presentation & Diagnosis of AKI

• Signs and symptoms of AKI vary based on underlying causes and can include:
  • Weight gain or loss (prerenal)
  • Gastrointestinal symptoms like nausea, vomiting, and diarrhea
  • Fatigue and shortness of breath
  • Pruritus and edema
  • Anuria with alternating polyuria (postrenal)
  • Colicky abdominal pain radiating to the groin (postrenal)
  • Electrolyte disturbances
• Signs of hypovolaemia: tachycardia, hypotension, postural hypotension, dry skin, sunken eyes, collapsed peripheral veins, and cold extremities.

Physical Examination Findings

• Increased blood pressure and peripheral edema may be observed.
• Changes in mental status, jugular venous distention, and pulmonary edema can indicate severity.
• Physical indicators include crackles in the lungs and asterixis (involuntary jerking).
• Hypotension or orthostatic hypotension might present in prerenal AKI, along with rashes from intrinsic causes.

AKI Staging System

• Based on serum creatinine changes as per South African Renal Society (SARS) guidelines from 2015.
• BUN-to-creatinine ratio > 10:1 can suggest prerenal AKI due to increased urea reabsorption at lower urine flow rates.
• FENa (fractional excretion of sodium) differentiates AKI types; < 1% indicates prerenal AKI due to enhanced sodium reabsorption.

Laboratory Tests

• Full blood count (FBC) may show elevated white blood cell count indicative of infection.
• Arterial blood gases can reveal metabolic acidosis.
• Urea & Electrolytes (U & E):
  • Elevated serum creatinine (SCr) reference range: 53 to 106 µmol/L.
  • Elevated BUN (reference range: 2.9 to 8.9 mmol/L).
  • Hyperkalaemia might be present.
• Urinalysis findings:
  • Different appearances can indicate specific underlying conditions, such as brown muddy casts for intrinsic ATN or eosinophiluria for acute interstitial nephritis.

Case Study Findings

• Example patient is a 65-year-old woman with stage 2 chronic kidney disease and presenting symptoms including nausea, vomiting, and weight gain due to edema.
• Her blood pressure is elevated at 170/94 mmHg, and crackles are observed on auscultation.
• Medications include losartan, hydrochlorothiazide, ibuprofen, and others, which may contribute to AKI risk.

Questions for Further Assessment

• Signs and symptoms of AKI:
  • Bilateral pitting edema, weight gain, elevated blood pressure, crackles, and general weakness suggest AKI.
• Risk factors for developing AKI include age, history of diabetes and chronic kidney disease, and medication use (especially NSAIDs).
• Additional laboratory information needed includes comprehensive blood chemistry tests (BUN, SCr, bicarbonate, potassium), WBC count, previous lab results to assess baseline kidney function, urinalysis, and results related to glucose management.
• Key pharmacotherapy questions include duration and dosages of ibuprofen and other medications, adherence to prescriptions, and use of additional medications.