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Renal Adverse Effects of Medications Commonly Taken by HIV-Infected Persons

for Health Care Providers

Table 3. Renal Adverse Effects of Medications Commonly Taken by HIV-Infected Persons

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DrugDisorder/ PathologyFindingsComments/ Suggestions
TDFTDF-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.
Proximal tubular injury (ATN)Fanconi syndrome (metabolic acidosis, ↑ Cr, ↓ serum K+ and phosphate, ↑ urine bicarbonate, phosphate, and glucose)
ATVNephrolithiasisSymptoms 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.
IDVAIN↑ Cr, pyuria
  • Usually resolves with drug discontinuation; may require steroids.
CrystalluriaAsymptomatic, 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.
NephrolithiasisRenal 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.
AcyclovirCrystalluriaMay precipitate ARF
  • Treat with hydration; avoid rapid intravenous bolus; adjust dosage for renal function.
Amphotericin BIncreased 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.
CidofovirProximal 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.
FoscarnetATN
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.
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.
TMP-SMXHyperkalemia 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.
Impaired tubular secretion of Cr↑ Cr
  • Hyperkalemia often appears after 1 week of therapy.
  • Consider monitoring serum K+, especially with high-dose therapy.

From Renal Disease
Primary Care of Veterans with HIV
Office of Clinical Public Health Programs
Veterans Health Administration, 2009