Three measures confirm 144-week renal record of tenofovir
Mark Mascolini for NATAP.org
Two formulas to calculate glomerular filtration rate – a signal of kidney trouble – figured no significant change during 144 weeks of tenofovir therapy in the randomised trial comparing tenofovir with d4T . Development of chronic kidney disease, as defined by the National Kidney Foundation, did not differ between the tenofovir and d4T groups.
With coworkers in Germany and Britain, Joel Gallant from Johns Hopkins University in Baltimore ran this 144-week, double-blind, placebo-controlled trial of tenofovir or d4T plus 3TC and efavirenz in 600 previously untreated people. The trial excluded people with pretreatment portents of kidney problems.
Gallant used the Cockcroft-Gault equation and the Modification of Diet and Renal Disease (MDRD) formula to figure glomerular filtration rates in the two study arms at study week 144. A lower Cockcroft-Gault or MDRD score indicates worse creatinine clearance. Gallant noted that either equation gauges kidney function better than simply measuring serum creatinine, though the MDRD seems more accurate in people without HIV who have chronic kidney disease. However, the MDRD formula has not been validated in people with normal kidney function or in people with HIV. (See note 2 for the equations. Online Cockcroft-Gault and MDRD calculators can be found at http://nephron.com/mdrd/default.html).
Table 1: Glomerular filtration rates at 144 weeks in the tenofovir-vs-d4T trial
|Tenofovir arm (n=299)||d4T arm (n=301)|
|Mean Δ at wk 144||+2||+7 *|
|Modification of diet in renal disease (ml/min/1.73m2)|
|Mean Δ at wk 144||-2||+9 *|
|Kidney disease stage (glomular filtration rate by MDRM)|
|Stg 0/1 (GFR >90) baseline||88%||84%|
|Stg 2 (GFR 60-89) baseline||12%||14%|
|Stg 3 (GFR 30-59) baseline||<1%||<1%|
|Stg 0/1 (GFR >90) week 144||69%||71%|
|Stg 2 (GFR 60-89) week 144||30%||27%|
|Stg 3 (GFR 30-59) week 144||1%||1%|
|Stg 4 (GFR 15-29) week 144||0%||<1%|
GFR = Glomular filtration rate * P <0.05
Baseline glomerular filtration rates by either equation and National Kidney Foundation kidney disease stage proved similar in the two treatment arms. After 144 weeks of tenofovir or d4T, glomerular filtration rates did not change significantly in the tenofovir group, though they did rise significantly among people taking d4T (Table 1).
Glomerular filtration rate reckoned by the Cockcroft-Gault equation did not change significantly in either treatment arm among people taking antihypertensives or antidiabetes drugs during the study.
No one in the trial stopped tenofovir because of kidney problems, and study clinicians never diagnosed proximal renal tubular dysfunction or Fanconi syndrome through 144 weeks.
In a separate retrospective look at clinical trial data, Glaxo researchers unearthed no evidence of significant changes in glomerular filtration rate after previously untreated people took efavirenz plus Trizivir (AZT/3TC/abacavir), Combivir (AZT/3TC), or 3TC/abacavir for 48 weeks .
References and notes:
- Gallant J, Staszewski S, Pozniak A, et al. Similar renal safety profile between tenofovir DF and stavudine (d4T) using modification of diet in renal disease and Cockcroft-Gault estimation of glomerular filtration rate in antiretroviral-naive patients through 144 weeks. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy. December 16-29, 2005. Washington, DC. Abstract H-350.
- Cockcroft-Gault equation: glomerular filtration rate (mL/min) = (140 – age in years) x weight in kg divided by (72 x serum creatinine in mg/dL) x (0.85 if female). Modification of Diet in Renal Disease equation: glomerular filtration rate (mL/min/1.73 m2)= 186 x serum creatinine in mg/dL(-1.154) x age in years(-0.203) x 0.742 if female x 1.212 if black.
- Sutherland-Phillips D, Hill-Zabala C, Brothers Q, et al. Regimens containing abacavir, lamivudine, zidovudine, and efavirenz do not affect glomerular filtration rate during long-term treatment of HIV-naive subjects. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy. December 16-29, 2005. Washington, DC. Abstract H-349.