What drugs can cause intratubular obstruction?

Drugs Causing Intratubular Obstruction

Several medications can cause acute kidney injury through intratubular crystal precipitation and obstruction, including acyclovir, methotrexate, sulfonamides, indinavir, and triamterene. 1

Common Medications Causing Intratubular Obstruction

Antiviral Agents

• Acyclovir: Can precipitate in renal tubules when its solubility (2.5 mg/mL) is exceeded in intratubular fluid, especially after bolus injections or inappropriately high doses 2
• Indinavir: Associated with crystalluria, which can lead to renal parenchymal filling defects and gradual loss of renal function 3
• Foscarnet: Can form crystals leading to acute renal failure 3, 4

Chemotherapeutic Agents

• Methotrexate: Can precipitate in renal tubules, particularly with high-dose therapy. Prevention requires hydration, urinary alkalinization, and monitoring of serum levels 5

Antibiotics

• Sulfonamides (including trimethoprim-sulfamethoxazole): Form crystals that are insoluble in human urine 1

Diuretics

• Triamterene: Associated with crystal formation and intratubular precipitation 1

Risk Factors for Crystal-Induced Nephropathy

1. Volume depletion: Decreases urine flow and increases drug concentration in tubules 1
2. Pre-existing renal impairment: Reduces drug clearance, leading to higher concentrations 1, 6
3. Acidic urine: Promotes crystallization of certain drugs (especially acyclovir, methotrexate) 1
4. High drug doses: Increases risk of exceeding solubility threshold 2
5. Rapid intravenous administration: Leads to high peak concentrations 3

Pathophysiology

Intratubular obstruction occurs through several mechanisms:

• Crystal formation within tubular lumens
• Precipitation of the drug when its solubility is exceeded
• Tubular dilatation due to high hydrostatic pressure
• Secondary inflammation and cellular damage 7
• Extrinsic compression of tubules 7

Prevention Strategies

1. Adequate hydration: Maintain high urinary flow (at least 1.5 liters of water daily) 3
2. Urinary alkalinization: When appropriate (for acidic drugs like methotrexate) 1
3. Appropriate drug dosing: Adjust doses based on renal function 3
4. Avoid rapid intravenous bolus: Use slower infusion rates for high-risk medications 3
5. Monitor renal function: Check creatinine clearance and electrolytes regularly 3
6. Avoid concurrent nephrotoxic drugs: Combinations increase risk 6

Management of Established Crystal Nephropathy

1. Discontinue the offending drug if possible 1
2. Volume repletion: Restore intravascular volume 1
3. Urinary alkalinization: For appropriate medications 1
4. Dialytic support: May be necessary in severe cases 1
5. Specific antidotes: For certain drugs (e.g., leucovorin for methotrexate) 5

Clinical Pearls

• Crystal nephropathy often presents as non-oliguric acute kidney injury
• The onset can be rapid, within hours to days of drug administration
• Recovery is usually possible if the condition is recognized early and managed appropriately
• Hemodialysis may help clear some drugs (like methotrexate) but is not universally effective 5
• The onset of tubular obstruction in a few tubules is often underestimated, especially in patients with chronic kidney disease 7

Awareness of these medications and appropriate preventive measures can significantly reduce the risk of this potentially serious but often preventable form of acute kidney injury.