Predictors of advanced chronic kidney disease and end-stage renal disease in HIV-positive persons

Ryom, Lenea; Mocroft, Amandab; Kirk, Olea; Ross, Michaelc; Reiss, Peterd; Fux, Christophe A.e; Morlat, Philippef; Moranne, Olivierg; Smith, Coletteb; El-Sadr, Wafaah; Law, Matthewi; Lundgren, Jens D.a

doi: 10.1097/QAD.0000000000000042
Clinical Science

Objectives: Whilst several antiretroviral drugs have been associated with moderate chronic kidney disease (CKD), their contribution to advanced CKD and end-stage renal disease (ESRD) remain unknown.

Design: D:A:D participants with at least three estimated glomerular filtration rates (eGFR) after February 2004 were followed until the first of advanced CKD (confirmed eGFR ≤ 30 ml/min, ≥3 months apart), ESRD (dialysis ≥3 months/ transplantation), 6 months after last visit or February 2012.

Methods: Poisson regression was used to assess risk factors for advanced CKD/ESRD including exposure to potential nephrotoxic antiretroviral drugs and antiretroviral drug discontinuation rates according to latest eGFR.

Results: Among 35 192 persons contributing 200 119 person years of follow-up (PYFU), 135 (0.4%) developed advanced CKD (n = 114)/ESRD (n = 21); incidence rate = 0.67 [95% confidence interval (CI), 0.56–0.79]/1000 PYFU. Tenofovir (TDF) was particularly frequently discontinued as eGFR declined. After adjustment, those previously exposed but currently off TDF had similar advanced CKD/ESRD rate ratios compared with those unexposed [1.00 (95% CI, 0.66–1.51)], while those currently on TDF had reduced rates [0.23 (95% CI, 0.13–0.41)]. No consistent associations with other antiretroviral drugs were seen. Results were robust after time-lagging antiretroviral drug exposure, stratifying by baseline eGFR, and allowing for competing risks. Other predictors were diabetes, hypertension, baseline eGFR, smoking and current CD4+ cell count. The incidence rate in nonsmokers with baseline eGFR > 60 and no diabetes or hypertension was 0.16 (95% CI 0.09–0.26)/1000 PYFU.

Conclusion: Neither current nor recent antiretroviral drug use predicted advanced CKD/ESRD during 6 years median follow-up in a large, heterogenenous and primarily white cohort. TDF discontinuation rates increased with decreasing eGFR, leaving a selected group still on TDF at lower advanced CKD/ESRD risk. Traditional renal risk factors and current CD4+ cell count were the strongest advanced CKD/ESRD predictors.

Author Information

aCopenhagen HIV Programme, University of Copenhagen, Faculty of Health and Medical Sciences and Epidemiklinikken M5132, Copenhagen University Hospital/Rigshospitalet, Copenhagen, Denmark

bResearch Department of Infection and Population Health, UCL, London, UK

cDivision of Nephrology, Mount Sinai School of Medicine, New York, USA

dAcademic Medical Center, University of Amsterdam, and Stichting HIV Monitoring, The Netherlands

eClinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Switzerland

fService de médecine interne et maladies infectieuses, Hôpital Saint-André, CHU de Bordeaux

gNephrology Department, Public Health Department, CHU Nice, France

hICAP-Columbia University and Harlem Hospital, New York, USA

iKirby Institute, Sydney, Australia.

Correspondence to Lene Ryom, MD, Copenhagen HIV Programme, University of Copenhagen, Faculty of Health Sciences The Panum Institute/Building 21.1 Blegdamsvej 3B, 2200 Copenhagen, Denmark. Tel: +45 35 45 57 57; fax: +45 35 45 57 58; e-mail:

Received 9 April, 2013

Revised 20 August, 2013

Accepted 21 August, 2013

© 2014 Lippincott Williams & Wilkins, Inc.