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  20th Conference on Retroviruses and
Opportunistic Infections
Atlanta, GA March 3 - 6, 2013
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Lower Current CD4s--But Not Tenofovir--Predict Advanced CKD/ESRD in D:A:D
  20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
"The advanced CKD/ESRD incidence rate in those with baseline eGFR>60 mL/min and no diabetes,
hypertension or smoking was 0.16 (95%CI 0.09-0.26)/1000 PYFU."
"Receipt of non-ARV nephrotoxic drugs, proteinuria and a family history of renal disease may represent unmeasured confounding."

Mark Mascolini
A lower current CD4 count raised chances of advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD) in the D:A:D Study [1]. During follow-up, cohort members stopped tenofovir (TDF) as estimated glomerular filtration rate (eGFR) declined. People who took TDF then stopped had an advanced CKD/ESRD rate similar to that of people who never took TDF.
Accumulating research addresses the impact of antiretroviral therapy (ART) and classic risk factors on CKD but not advanced CKD or ESRD. To address that question, D:A:D researchers studied cohort members with 3 or more eGFR measurements starting January 1, 2004 and without advanced CKD/ESRD when follow-up began. Follow-up continued until a person had advanced CKD/ESRD, 6 months after the last study visit, or January 2, 2012. The D:A:D team defined advanced CKD as two eGFRs below 30 mL/min/1.73 m(2) at least 3 months apart; ESRD meant dialysis for at least 3 months or kidney transplantation.
The study included 35,192 people with 200,119 person-years of follow-up. Three quarters (74%) were men, 48% Caucasian, 46% gay or bisexual men, and 40.5% current smokers; 9% had hypertension and 4% had diabetes. Only 3% had a baseline eGFR between 30 and 60 mL/min, while 23% had a baseline eGFR between 60 and 90 and the rest were over 90. Median baseline eGFR stood at 107 mL/min (interquartile range [IQR] 96 to 127), median CD4 count at 437 (IQR 289 to 620), and median age at 41 (IQR 38 to 48). Cohort members had HIV infection for a median of 6.1 years (IQR 1.5 to 11.8).
Through a median follow-up of 6.2 years (IQR 4.1 to 7.6), advanced CKD/ESRD developed in 135 people (0.4%), 114 with CDK and 21 with ESRD. Incidence stood at 0.67 per 1000 person-years (95% confidence interval [CI] 0.56 to 0.79). Five years from baseline, progression to advanced CKD/ESRD was estimated at 0.32 per 1000 person-years (95% CI 0.26 to 0.38). The adjusted rates of switching away from atazanavir/ritonavir, lopinavir/ritonavir, and TDF rose as current eGFR fell; with TDF that rise in switching was exponential (see Figure 2 in poster linked below).
A Poisson regression model to identify variables associated with advanced CKD/ESRD adjusted for age, gender, ethnicity, HIV transmission group, enrollment cohort, prior AIDS, HBV and HCV status, smoking, hypertension, diabetes, cardiovascular events, baseline year, eGFR, current CD4 count, nadir CD4 count, viral load, and use of TDF and protease inhibitors. In this analysis people who stopped TDF during follow-up had advanced CKD/ESRD rates similar to those of people who never took TDF. Other antiretrovirals analyzed had no significant impact on advanced CKD/ESRD risk.
This regression analysis also determined that every doubling of current CD4 count lowered the risk of advanced CKD/ESRD 27% (incidence rate ratio [IRR] 0.73, 95% CI 0.64 to 0.84). Compared with current smokers, people who never smoked had a 44% lower risk of advanced CKD/ESRD (IRR 0.56, 95% CI 0.34 to 0.93). Three other classic risk factors raised the risk of advanced CKD/ESRD:
-- Diabetes: IRR 3.29, 95% CI 2.18 to 4.98
-- Hypertension: IRR 2.48, 95% CI 1.70 to 3.62
-- Lower baseline eGFR: IRR 2.05 per 10 mL/min, 95% CI 1.86 to 2.26
For nonsmokers with baseline eGFR above 60 mL/min and without diabetes or hypertension, advanced CKD/ESRD incidence was 0.16 per 1000 person-years (95% CI 0.09 to 0.26).
The researchers cautioned that their analysis could not factor in use of nonantiretroviral nephrotoxic drugs, proteinuria, or family history of kidney disease.
They concluded that current or recent use of antiretrovirals considered nephrotoxic did not affect chances of advanced CKD/ESRD. But they noted that switches away from these antiretrovirals as eGFR dropped "likely play a central role [in] the lack of an observed antiretroviral association." The D:A:D team warned that their findings "do not exclude the possibility that such antiretroviral relations may exist in populations without access to regular eGFR screening." More prolonged use of these antiretrovirals than assessed in this study, they added, could also have an impact "in an older HIV-positive population at higher underlying risk of renal impairment."
1. Ryom L, Mocroft A, Kirk O, et al. Predictors of advanced chronic kidney disease and end-stage renal disease in HIV+ persons: D:A:D. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 810. http://www.retroconference.org/2013b/PDFs/810.pdf
Predictors of Advanced Chronic Kidney Disease and End-Stage Renal Disease in HIV-Positive Persons in D:A:D
L Ryom1, A Mocroft2, O Kirk1, M Ross3, P Reiss4, W El-Sadr5, S de Wit6, P Morlat7, O Moranne8, CA Fux9, A d'Arminio Monforte10, M Law11 and JD Lundgren1 for the D:A:D Study group
1Copenhagen HIV Programme, University of Copenhagen, Faculty of Health Sciences and Epidemiklinikken M5132, Copenhagen University Hospital/Rigshospitalet, Copenhagen, Denmark; 2Research Department of Infection and Population Health, UCL, London, United Kingdom; 3Division of Nephrology, Mount Sinai School of Medicine, New York, USA; 4Academic Medical Center, Division of Infectious Diseases and Department of Global Health, University of Amsterdam, The Netherlands; 5ICAP-Columbia University and Harlem Hospital, New York, United States; 6CHU Saint-Pierre,
Department of Infectious Diseases, Brussels, Belgium; 7Universite Bordeaux Segalen, INSERM U 897, CHU de Bordeaux, France; 8Nephrology Department, Public Health Department, CHU Nice, France; 9Clinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Switzerland; 10Dipartimento di Scienze della Salute, Clinica di Malattie Infectitive e Tropicali, Azienda Ospedaliera-Polo Universitario San Paolo, Milan Italy; 11Kirby Institute, Sydney, Australia