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 persons with HIV)
  • 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
 ATV
(DRV)		 Assessment:
  • Urinalysis for crystalluria/stone analysis
  • Exclude other cause for nephrolithiasis
  • Renal tract imaging including CT scan

Consider stopping 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
 ATV

Assessment:

  • Renal ultrasound
  • Refer to nephrologist

Consider stopping 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)

In persons with ART-associated nephrotoxicity some data to suggest eGFR improvement may take time after discontinuation of the offending agent, and the potentials for improvement are higher the shorter duration of nephrotoxic ART use, the higher eGFR at discontinuation and the younger the age.

* 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