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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Nephrotoxic Effects

(Last updated: February 12, 2014; last reviewed: February 12, 2014)

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Table 11i. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Nephrotoxic Effects
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Urolithiasis/ nephrolithiasis IDV, ATV Onset
  • Weeks to months after starting therapy
Clinical findings:
  • Crystalluria, hematuria, pyuria, flank pain, sometimes increased creatinine
IDV-related nephrolithiasis is more common in adults (4%–43%) than in children (0%–20%).

ATV nephrolithiasis is rare.
In adults, high serum IDV concentrations and elevated urine pH (>5.7) associated with persistent pyuria.

Unknown in children.

  • Maintain adequate hydration.
  • Obtain urinalysis at least every 6–12 months.
Provide adequate hydration and pain control; consider using alternative ARV.
TDF Onset
  • Variable; in adults, weeks to months after initiation of therapy.
  • Hypophosphatemia appears at a median of 18 months.
More Common
  • Increased serum creatinine, proteinuria. Hypophosphatemia, usually asymptomatic, may present with bone and muscle pain, weakness.
Less Common
  • Renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis, nephrogenic diabetes insipidus with polyuria
  • ~2% with increased serum creatinine
  • ~0.5% with severe renal complications
  • ~4% with hypophos-phatemia or proximal tubulopathy; higher in advanced HIV infection or concomitant use of ddI
Risk May Be Increased in Children:
  • aged >6 years
  • of Black race, Hispanic/
    Latino ethnicity
  • with advanced HIV infection
  • with concurrent use of ddI or PIs (especially LPV/r), and 
    pre-existing renal dysfunction
  • Risk increases with longer duration of TDF treatment.
Monitor urine protein and glucose or urinalysis, and serum creatinine at intervals of every 3–6 months. For patients taking TDF, some panelists add serum phosphate to the list of routine labs to monitor.

In the presence of persistent proteinuria or glucosuria, or for symptoms of bone pain or muscle pain or weakness, also monitor serum phosphate

Because toxicity risk increases with duration of TDF treatment, frequency of monitoring should not decrease with time. While unproven, routine monitoring intervals of every 3–6 months might be considered. Abnormal values should be confirmed by repeat testing, and frequency of monitoring can be increased if abnormalities are found and TDF is continued.
If TDF is the likely cause, consider using alternative ARV. 
IDV Renal cortical atrophy, acute renal failure Rare Unknown Unknown If IDV is likely cause, consider using alternative ARV. 

Note: IDV not FDA-approved for use in children.
Key to Acronyms: ARV = antiretroviral;, ATV = atazanavir; ddI = didanosine; IDV = indinavir; LPV/r = ritonavir-boosted lopinavir; PI = protease inhibitor; TDF = tenofovir disoproxil fumarate


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