| TDF | TDF-associated renal insufficiency | ↑ Cr, usually small; slight (4% vs other NRTIs) decrease in eGFR over time | - Of unclear clinical significance, but warrants monitoring of renal function.
- May be associated with duration of HIV infection, concomitant RTV-boosted PIs (which boost TDF levels), preexisting renal dysfunction, or diabetes.
- Check serum and urine electrolytes, eGFR, and UA before starting therapy; check serum electrolytes and eGFR every 3-6 months on TDF; check UA every 6 months. Consider more frequent monitoring in patients with eGFR ≤90 mL/min/1.73 m2, renally secreted drugs, RTV-boosted PIs, diabetes, or hypertension.
- Adjust TDF dosage based on steady-state CrCl.
- Rare, usually resolves with discontinuation of TDF, but can lead to permanent damage, ESRD.
- May be more likely in patients with preexisting renal disease.
- Check serum and urine electrolytes, eGFR, UA before starting therapy and every 6 months on therapy, especially in patients with eGFR ≤90 mL/min/1.73 m2, renally secreted drugs, RTV-boosted PIs (which boost TDF levels), diabetes, or hypertension.
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| Proximal tubular injury (ATN) | Fanconi syndrome (metabolic acidosis, ↑ Cr, ↓ serum K+ and phosphate, ↑ urine bicarbonate, phosphate, and glucose) |
| ATV | Nephrolithiasis | Symptoms of renal colic, dysuria, urgency; mild ↑ Cr; ATV-containing stones | - Case reports.
- Treat with hydration; if symptoms do not resolve, or if symptoms recur, may need to discontinue drug.
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| IDV | AIN | ↑ Cr, pyuria | - Usually resolves with drug discontinuation; may require steroids.
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| Crystalluria | Asymptomatic, or symptoms of renal colic, dysuria, urgency; crystals on UA; mild ↑ Cr | - Treat with hydration.
- If manifestations do not resolve, may need to discontinue drug.
- Not necessary to discontinue for asymptomatic crystalluria.
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| Nephrolithiasis | Renal colic, dysuria, urgency; mild ↑ Cr; crystals on UA; stones or filling defects on radiography | - Risk reduced by drinking 1.5-2 liters of liquids per day.
- Treat with hydration; if symptoms do not resolve, or if symptoms recur, may need to discontinue drug.
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| Acyclovir | Crystalluria | May precipitate ARF | - Treat with hydration; avoid rapid intravenous bolus; adjust dosage for renal function.
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| Amphotericin B | Increased tubular permeability and/or renal vasoconstriction | ↑ Cr, ↓ serum K+ and Mg++, ↓ urine bicarbonate; distal renal tubular acidosis; non-anion-gap metabolic acidosis | - More severe renal failure likely with concurrent nephrotoxins (aminoglycosides, foscarnet), diuretic use, hypovolemia, chronic renal failure.
- Hydration with normal saline is somewhat protective.
- Switch to lipid formulation of amphotericin B for rise in Cr of >2.5 mg/dL while on conventional amphotericin B; continue to monitor electrolytes.
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| Cidofovir | Proximal tubular injury | (See TDF, above) | - Incidence reduced with hydration (normal saline) and probenecid, which blocks absorption of drug by tubular epithelial cells.
- Check Cr and urine protein within 48 hours before each dose and reduce dosage for decreased CrCl or eGFR.
- Discontinue drug for either Cr ≥0.5 mg/dL above baseline or proteinuria ≥3+ on dipstick analysis.
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| Foscarnet | ATN
Crystal deposition | ↑ Cr, ↓ serum Ca++, Mg++, phosphorus; sometimes↑ serum Ca++ and phosphorus | - Cr generally increases after 1-2 weeks of foscarnet therapy.
- Renal toxicity is reduced with infusion of 0.5-1 liter of normal saline with or before foscarnet.
- Toxicity is more likely with concomitant nephrotoxins.
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| Pentamidine (IV, rarely aerosolized) | Tubular toxicity (ATN) | ↑ Cr, ↑ serum K+; ↓ serum Mg++ and Ca++ | - Discontinuation of pentamidine reverses toxicity, although that process can take several weeks.
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| TMP-SMX | Hyperkalemia caused by blockage of Na+ channel in collecting tubule | ↑ Serum K+ | - Usually seen with high-dose therapy (eg, PCP treatment), but sometimes seen with lower dosages.
- Hyperkalemia more common with preexisting renal insufficiency.
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| Impaired tubular secretion of Cr | ↑ Cr | - Hyperkalemia often appears after 1 week of therapy.
- Consider monitoring serum K+, especially with high-dose therapy.
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