ARV-associated Nephrotoxicity

 Renal abnormality* ARV  Management

Proximal tubulopathy with any combination of:

  1. Proteinuria: urine dipstick ≥ 1, or confirmed increase in UP/C >15 mg/mmoL(i)
  2. Progressive decline in eGFR and eGFR ≤ 90 mL/min(ii)
  3. Phosphaturia(iii): confirmed hypophosphataemia secondary to increased urine phosphate leak
  4. Glucosuria in non-diabetics
 TDF**

Assessment:

  • Tests for proximal renal tubulopathy/renal Fanconi syndrome(iii) (less frequent in Black PLWH)
  • Consider renal bone disease if hypophosphataemia of renal origin: measure 25(OH) vitamin D, PTH, DXA

Replace TDF by non-tenofovir drug or TAF*** if:

  • Documented tubular proteinuria and/or glucosuria                   
  • Progressive decline in eGFR and no other cause
  • Confirmed hypophosphataemia of renal origin and no other cause
  • Osteopenia/osteoporosis in the presence of increased urine phosphate leak
Nephrolithiasis:
  1. Crystalluria
  2. Haematuria(iv)
  3. Leukocyturia
  4. Loin pain
  5. Acute renal insufficiency
 IDV
ATV
(DRV)		 Assessment:
  • Urinalysis for crystalluria/stone analysis
  • Exclude other cause for nephrolithiasis
  • Renal tract imaging including CT scan

Consider stopping IDV/ATV if:

  • Confirmed renal stones
  • Recurrent loin pain +/- haematuria
Interstitial nephritis:
  1. Progressive decline in eGFR(ii)
  2. Tubular proteinuria(ii)/haematuria
  3. Eosinophiluria (if acute)
  4. Leukocyte casts
 IDV
ATV

Assessment:

  • Renal ultrasound
  • Refer to nephrologist

Consider stopping IDV/ATV if:

  • Progressive decline in eGFR and no other cause

Progressive decline in eGFR, but none of the above(v)

 TDF**
PI/r

Complete assessment

Consider stopping ARVs with potential nephrotoxicity if:

  • Progressive decline in eGFR and no other cause(v)

 

* Use of DTG, BIC, RPV, COBI and PI/b is associated with an increase in serum creatinine/reduction of eGFR (10-15 mL/min or up to 25%) due to inhibition of proximal tubular creatinine transporters without impairing actual glomerular filtration: consider new set point after 1-2 months

** TAF has shown lower tenofovir-related renal adverse effects due to lower systemic tenofovir exposure. Switch-studies from TDF to TAF and certain PIs suggest potential reversion of renal toxicity, however, longterm experience with TAF is lacking

*** There are limited data on use of TAF with low eGFR, particularly eGFR ≤ 10 mL/min

  1. UP/C in spot urine detects total urinary protein including protein of glomerular or tubular origin. The urine dipstick analysis primarily detects albuminuria as a marker of glomerular disease and is inadequate to detect tubular disease
  2. For eGFR: use CKD-EPI formula based on serum creatinine, gender, age and ethnicity because eGFR quantification is validated > 60 mL/ min. The abbreviated modification of diet in renal disease (aMDRD) or the Cockcroft-Gault (CG) equation may be used as an alternative; see https://www.chip.dk/Tools-Standards/Clinical-risk-scores
  3. See Indications and Tests for Proximal Renal Tubulopathy (PRT)
  4. Microscopic haematuria is usually present
  5. Different models have been developed for calculating 5-year CKD risk score while using different nephrotoxic ARVs integrating HIV-independent and HIV-related risk factors
  6. RTV used as a boosting agent may induce nephrosclerosis