The significance of antiretroviral-associated acute kidney injury in a cohort of ambulatory human immunodeficiency virus-infected patients

Nephrol Dial Transplant. 2013 Aug;28(8):2073-81. doi: 10.1093/ndt/gft210. Epub 2013 Jun 5.


Background: To determine the incidence and significance of acute kidney injury (AKI) after initiating highly active antiretroviral therapy (HAART).

Methods: A prospective cohort study of 271 consecutively treated HIV-infected patients, initiating first (75) or sequential HAART (196) from January 2008 to June 2011. AKI was diagnosed according to the Risk, Injury, Failure, Loss of kidney function, End-stage renal disease (RIFLE)/Acute Kidney Injury Network (AKIN) criteria, and the risk of progression to chronic kidney disease (CKD) was evaluated.

Results: A greater estimated glomerular filtration rate (eGFR) decrease after 1 year was observed for patients initiating a tenofovir disoproxil fumarate (TDF)-based regimen (-6.45 versus +0.98 mL/min/1.73 m(2) when compared with patients without TDF; P < 0.01), both in the case of the first (-8.5 versus -2.27; P = 0.04) or successive regimens (-5.3 versus + 1.18 mL/min/1.73 m(2); P < 0.01). AKI, as defined, was observed in 10% (28 cases, 6.98 episodes/100 patients-year), mostly stage I (27 cases), in a median time of 6 (3-16.5) months. Four cases (14%), having a worse baseline renal function progressed to CKD, whereas four recovered completely. In the multivariate analysis, AKI was associated with the concomitant use of cotrimoxazole prophylaxis and to low CD4+ count. CKD was diagnosed in 2% (six cases) of patients. Therefore, the overall rate of HAART-associated renal disorders was 11% (30 cases, 7.46 episodes/100 patients-year (95% confidence interval, 6.09-8.83).

Conclusions: The initiation of a tenofovir-based regimen is followed by a significant decline in eGFR, although it could be misinterpreted by the concomitant use of cotrimoxazole. A substantial proportion of patients develop AKI, but only a minority progress to CKD. Patients initiating HAART and developing AKI should be carefully monitored for progression of renal disease.

Keywords: AKI; antiretroviral; cotrimoxazole nephrotoxicity; outcome; tenofovir.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / virology
  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adult
  • Anti-HIV Agents / adverse effects*
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • HIV / drug effects
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • Humans
  • Kidney Function Tests
  • Male
  • Organophosphonates / adverse effects*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Tenofovir


  • Anti-HIV Agents
  • Organophosphonates
  • Tenofovir
  • Adenine