Acute Kidney Injury: Definition and Diagnosis

Acute Kidney Injury (AKI)

• A common diagnosis in hospitalized patients affecting 5-10% of hospitalized patients and up to 60% of critical care patients.
• Significantly increases short and long-term morbidity and mortality rates.
• Caused by a variety of factors, including disease processes and drugs.

AKI: Definition

• Defined as an acute decrease in kidney function (GFR) over hours, days, or weeks.
• Characterized by waste product accumulation and volume overload.

AKI Diagnostic Criteria

- Serum creatinine rises by ≥ 26 µmol/L within 48 hours.
- Serum creatinine rises ≥ 1.5 fold from baseline within 7 days.
- Urine output is < 0.5ml/kg/hr for ≥ 6 consecutive hours.

AKI Staging

• Stage 1: Serum creatinine increase ≥ 26 μmol/L within 48 hours or urine output <0.5 ml/kg/hr for ≥ 6 hours.
• Stage 2: Serum creatinine increase ≥ 50 μmol/L from baseline or urine output < 0.5 ml/kg/hr for ≥ 12 hours.
• Stage 3: Serum creatinine increase ≥ 354 μmol/L or commencement of renal replacement therapy (RRT) regardless of stage.

AKI Risk Factors

• Pre-existing CKD
• Volume depletion
• Nephrotoxic agents
• Urinary tract obstruction

AKI Assessment

• Past medical history, including renal disease-related conditions (hypertension, diabetes).
• Medication history
• Patient symptoms, such as altered urinary habits, sudden weight gain, and flank pain.

AKI Assessment: Signs

• Edema
• Coloured or foamy urine
• Orthostatic hypotension
• Hypertension

AKI Assessment: Laboratory Tests

• Serum creatinine
• Urea/BUN (2.9-7.1 mmol/L)

Types of AKI (Prerenal, Intrarenal, Postrenal)

• Prerenal: Blood supply disruption to kidney.
• Intrarenal (intrinsic): Damage to kidney nephrons and interstitium.
• Postrenal: Obstruction in the collecting system (ureter, bladder, urethra).

Prerenal AKI

• Characterized by decreased renal blood flow.
• Caused by hypovolemia, heart failure, hypotension, and sepsis.

Intrarenal AKI

• Characterized by direct damage to the kidney.
• Includes acute tubular necrosis (ATN), acute interstitial nephritis (AIN), and glomerulonephritis.

Postrenal AKI

• Characterized by obstruction in the urinary tract.
• Caused by prostate hypertrophy, kidney stones, and bladder cancer.

Drug-Induced Kidney Injury (DIKI)

• Contributing factor in 19-25% of severe AKI cases.
• Higher prevalence in older adults (up to 66%).

DIKI: Mechanism

• Prerenal: ACE inhibitors/ARBs, NSAIDs, calcineurin inhibitors.
• Intrarenal: Amphotericin B, aminoglycosides, radiographic contrast dye.
• Postrenal: Acyclovir, indinavir, sulfonamide antibiotics.

Angiotensin Converting Enzyme Inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs)

• High-risk patients: Those with severe atherosclerotic disease, bilateral renal artery stenosis, acute/decompensated heart failure, severe CKD, and volume depletion.
• Examples: ACEi (Ramipril, Lisinopril, Perindopril), ARBs (Telmisartan, irbesartan, valsartan).

ACEi/ARBs: Mechanisms

• Prevent vasoconstriction of efferent arterioles, reducing glomerular hydrostatic pressure and leading to decreased GFR.

Aminoglycosides

• Mechanism: Direct nephrotoxicity to the proximal tubules.
• Urine findings: Muddy brown epithelial cell casts, free epithelial cells, high urine sodium (> 40 mmol/L), FeNa >3%.

Amphotericin B

• Mechanism: Direct toxicity to cells in the distal nephron, leading to cell death and impairment of renal filtration and concentration.

Amphotericin B: Risk factors

• Cumulative dose
• Pre-existing kidney disease
• Concomitant nephrotoxic drugs
• Dehydration or volume depletion.

Acute Interstitial Nephritis (AIN)

• Occurs in up to 3% of AKI cases.
• Presentation: Fever, rash, pyuria/hematuria, oliguria, metabolic acidosis, hyperkalemia, salt wasting.
• Mechanism: Hypersensitivity reaction causing lymphocytic infiltration of the interstitium.
• Implicated drugs: Penicillins, lithium.

Obstructive Nephropathy (postrenal AKI)

• Caused by problems in the ureters, bladder, and urethra.
• Requires involvement of both kidneys.
• Types: Renal tubular obstruction, extrarenal urinary tract obstruction, nephrolithiasis.

Obstructive Nephropathy: Mechanism

• Renal tubular obstruction: Intratubular precipitation of drug crystals (e.g., acyclovir) or tissue degradation products (e.g., rhabdomyolysis with statins).
• Extrarenal urinary tract obstruction: Males with BPH given anticholinergic drugs.
• Nephrolithiasis: Precipitation of stone-forming components into ureters (e.g., Indinavir).

Drug-Induced Stones

• Occur in 1-2% of all stones.
• Risk factors: Daily dose, duration of treatment, urinary excretion of drug or metabolite, solubility of drug or metabolite, concentration peaks in urine, rate of elimination, morphology of crystals.
• Common causes: Sulfonamides, cephalosporins, quinolones, furanes, primidone, methotrexate, guaifenisin, allopurinol, sulfasalazine, indinavir, nelfinavir, acyclovir, triamterene.

DIKI Summary

• Drugs can contribute to all three types of AKI.
• Focus on prevention: Identifying high-risk patients, avoiding drug use, and discontinuing drugs as soon as possible.
• Treatment is primarily supportive.
• Pharmacists play a crucial role in assessing patients at risk for DIKI both in hospital and community settings.

Test your knowledge on Acute Kidney Injury (AKI), a critical condition affecting many hospitalized patients. This quiz covers the definition, diagnostic criteria, and staging of AKI. Enhance your understanding of this significant health issue.