Acute Tubular Injury Quiz

Study Notes

Acute Tubular Injury/Necrosis

Aminoglycoside Nephrotoxicity:
- Accumulates in proximal tubules, causing oxidative stress and cellular necrosis.
- Enters through endocytosis due to its cationic nature, leading to tubular obstruction.
- Clinical Presentation: Gradual increase in serum creatinine (SCr), decreased urine output, seen 5-7 days after treatment.
- Diagnostics: Rising SCr and BUN, decreased creatinine clearance.
- Management: Discontinue therapy, use alternative antibiotics like penicillin.
Radiographic Contrast Media Nephrotoxicity:
- Causes renal vasoconstriction via the release of adenosine and endothelin, leading to ischemia and reduced renal blood flow.
- Clinical Presentation: Non-oliguric AKI, with SCr peaking 3-4 days after exposure.
- Management: Avoid nephrotoxic agents, hydrate, use low-osmolar contrast.
Cisplatin Nephrotoxicity:
- Accumulates in proximal tubular cells, causing oxidative damage and necrosis.
- Clinical Presentation: Polyuria, decreased serum magnesium, hypokalemia, and hypocalcemia.
- Management: Adjust doses, manage electrolyte disturbances.
Amphotericin B Nephrotoxicity:
- Binds to ergosterol in the kidney’s cell membrane, causing increased permeability and necrosis.
- Induces vasoconstriction in afferent arterioles.
- Clinical Presentation: Nonoliguric AKI, electrolyte wasting.
- Management: Switch to liposomal Amphotericin, replace electrolytes.

Osmotic Nephropathy

Drugs involved: Mannitol, intravenous immunoglobulin (IVIG) containing sucrose.
Mechanism: High osmolar drugs cause cellular swelling and vacuolization in proximal tubular cells.
Presentation: Oliguria 2-4 days after exposure; cellular swelling is evident.
Management: Discontinue the offending agent.

Hemodynamically Mediated Kidney Injury

ACEIs and ARBs:
- Dilate efferent arterioles, reducing glomerular pressure and thereby lowering glomerular filtration rate (GFR).
- Risk Factors: Patients with renal artery stenosis, CHF, or pre-existing kidney disease.
- Clinical Presentation: AKI with rise in serum creatinine.
- Management: Monitor SCr, discontinue if creatinine rises >30%. Initiate low dose.
NSAIDs and COX-2 Inhibitors:
- Inhibit prostaglandin synthesis, reducing afferent arteriolar dilation, leading to ischemia in conditions of reduced renal blood flow.
- Clinical Presentation: AKI within 2-7 days, weight gain, diminished urine output, elevated BUN, SCr, and blood pressure.
- Management: Stop NSAIDs and provide supportive care. Kidney function typically recovers in 3-5 days.
Cyclosporine & Tacrolimus:
- Causes vasoconstriction of afferent arterioles through increased thromboxane A2 and endothelin production, leading to reduced renal plasma flow and GFR.
- Clinical Presentation: Hypertension, hyperkalemia, decreased GFR.
- Management: Dose reduction, calcium channel blockers.
SGLT-2 Inhibitors:
- Can cause volume depletion and reduce renal perfusion.
- Lead to prerenal AKI by reducing glomerular filtration through vasoconstriction of the afferent arteriole via tubuloglomerular feedback.
- Clinical Presentation: AKI, volume depletion, and prerenal azotemia.
- Diagnostics: Elevated serum creatinine and decreased GFR, urinalysis for dehydration markers.
- Management: Discontinue the drug, ensure hydration, treat electrolyte imbalances, provide IV fluids for volume depletion.
Chimeric Antigen Receptor (CAR) T-Cell Therapy:
- Trigger a cytokine release syndrome, leading to acute kidney injury by causing endothelial damage.
- Clinical Presentation: AKI, tumor lysis syndrome.
- Management: Treat cytokine release syndrome with steroids, manage electrolyte abnormalities.