Kidney Disease: Definition, Diagnosis and Management

Diagnosis

Management

HIV-associated kidney disease(vi)

Prevention of progressive renal disease Comment
1. ART

Start ART immediately where HIV-associated nephropathy (HIVAN)(vii) or HIV immune complex disease strongly suspected. Immunosuppressive therapy may have a role in immune complex diseases. Renal biopsy to confirm histological diagnosis recommended
Consider discontinuing or replacing TDF** by non-tenofovir drug or by TAF*** if:

  • UP/C 15-50 mg/mmol (see tubulopathy section)
  • eGFR > 60 mL/min, but decrease in eGFR by 5 mL/min per year for at least 3 consecutive years or confirmed 25% eGFR decline from baseline
  • co-morbidities with a high risk of CKD (i.e. diabetes and hypertension)
  • body weight < 60kg
  • use of a PI/b as a third agent

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

  • eGFR ≤ 60 mL/min
  • UP/C > 50 mg/mmol
  • nephrotoxic comedication
  • previous TDF toxicity (proximal renal tubulopathy)

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

2. Start ACE inhibitors or angiotensin-II receptor antagonists if:

  • Hypertension and/or
  • Proteinuria

Monitor eGFR and K+ level closely on starting treatment or increasing dose

Blood pressure target: < 130/80 mmHg

General measures:

  • Avoid nephrotoxic drugs including NSAID
  • Lifestyle measures (smoking, weight, diet)
  • Treat dyslipidaemia(viii) and diabetes(ix)
  • Adjust drug dosages where necessary(v)
CKD and proteinuria are independent risk factors for CVD

 

  1. 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.
    Definition CKD: eGFR ≤ 60 mL/min for ≥ 3 months (see https://kdigo.org/guidelines/ckd-evaluation-and-management/). If not previously known to have CKD, confirm pathological eGFR within 2 weeks. Several medications and/or dietary elements or supplements may artificially increase serum creatinine and thus reduce eGFR without affecting UP/C, including the use of creatinine and protein supplements. Renal function should be reassessed after ceasing dietary supplements and/or, where available, using cystatin C-based eGFR measurements (in stable PLWH on ART). Use of DTG, BIC, RPV, RAL, COBI and RTV boosted PIs is also independently associated with increases in serum creatinine and reduction of eGFR (10-15 mL/ min or up to 25%) due to inhibition of proximal tubular creatinine transporters and/or intestinal transporters without impairing actual glomerular filtration. Consider a new set point after 1-2 months. Use of NSAID and recreational drugs may also affect renal perfusion and thereby cause transient creatinine increase 
  2. Urinalysis: use urine dipstick to screen for haematuria. To screen for proteinuria, use urine dipstick and if ≥ 1+ check urine albumin/creatinine (UA/C) to screen for glomerular disease or protein/creatinine (UP/C) to screen for both glomerular and tubular disease, see iii and ARV-nephrotoxicity. Proteinuria is defined as persistent if confirmed on ≥ 2 occasions > 2-3 weeks apart
  3. UA/C largely detects glomerular disease and can be used for screening for HIV-associated renal disease and in those with DM but is not appropriate for screening for tubular proteinuria secondary to drug nephrotoxicity (e.g. TDF), where UP/C should be used, (see Indications and Tests for Proximal Renal Tubulopathy and ARV-nephrotoxicity). KDIGO screening values for UA/C are: < 3, 3-30 and > 30 mg/mmoL and for UP/C: < 15, 15-50, > 50 mg/mmol. UA/C and UP/C ratio are calculated as urine protein albumin (or protein) (mg/L) / urine creatinine (mmol/L); may also be expressed as mg/mg. Conversion factor for mg to mmol creatinine is x 0.000884
  4. Repeat eGFR and urinalysis as per screening table, see Assessment of PLWH at Initial & Subsequent Visits
  5. See, Dose Adjustment of ARVs for Impaired Renal Function 
  6. Joint management with a nephrologist
  7. HIVAN suspected if black ethnicity & UAP/C > 30 mg/mmol & no haematuria
  8. See Dyslipidaemia 
  9. See Type 2 Diabetes 
  10. Different models have been developed for calculating a 5-years CKD risk score while using different nephrotoxic ARVs integrating HIV-independent and HIV-related risk factors