September 17, 2007
Hi. This is Ben Young from the University of Colorado Health Science Center and Rose Medical Center in Denver. I'm presenting this poster on an analysis of kidney function in patients with preexisting kidney disease who receive tenofovir [brand name: Viread; also known as TDF]-containing antiretroviral therapy in the HOPS [HIV Outpatient Study] cohort.
This analysis was done to identify patients who were largely excluded from previous clinical analyses or studies, insomuch that they initiated tenofovir therapy when they had preexisting kidney disease.
We also identified patients who had prior history of kidney disease, but started tenofovir with normal kidney function. So, overall, we identified 19 patients in total, six of whom had preexisting kidney disease, but normal function at entry, and 13 who had confirmed kidney dysfunction, measured either by having a creatinine greater than 1.5 or a creatinine clearance less than 50 mL/min.
Overall, again, 19 patients in the group. The median creatinine in the group was 1.7, with a calculated creatinine clearance of 56, and a glomerular filtration calculation of 49. Median time of follow-up was 13 months, with a median of five creatinine determinations over time. Seventeen of the 19 patients received a now inappropriate dose of tenofovir -- that is, 300 mg once daily.
In the follow-up period, three of the six patients with previous kidney dysfunction went on to have a change in National Kidney Foundation [NKF] stage -- in other words, a worsening in their kidney function. Two of the 13 patients who had current renal dysfunction went on to have change in function. In aggregate, that meant that the overall intra-patient change in creatinine at 12 months was a decrease of 0.8, and a change in glomerular filtration of 1.3.
So, overall, what this means to me is that, in this group of patients who have poor kidney function at baseline and risk of progression of kidney disease, a small but significant percentage of them go on to have a worsening in stage. And that's consistent with the hypothesis that tenofovir is associated with increased risk of kidney disease. So that conclusion is not novel or surprising.
What was surprising to me was that, of the patients with past kidney dysfunction, 50% of them did not go on to have worsening NKF stage, and 11 of 13 patients with current kidney disease, most of whom were actually (now we know) overdosed, actually didn't have worsening of kidney disease.
So, taken together, this means that tenofovir does place these patients at increased risk, compared to the general, otherwise healthy population for incident kidney disease. But when necessary, because of needs -- either because of drug resistance profiles or perhaps the need to treat coexisting hepatitis B -- then tenofovir might be an option that could be utilized with appropriate caution and ongoing monitoring.
So that's the clinical take home. So it may be fine to use tenofovir with these kind of patients. But this is a very, very small study.
Yes, absolutely. Actually, I think the word "fine" is significantly overstated. I think it says that if you were forced, because of clinical limitations and limitations in clinical choices, treatment choices, that you could entertain using this as an option. It wouldn't be my first option in this patient population by any stretch. Indeed, with newer knowledge about how to mitigate safety and risk of other nucleosides, I think that in patients who have preexisting renal disease, if there are other options, I'm looking carefully at those other options. But this does say that if there are no other options, this might be something that could be entertained -- certainly better than not being able to suppress their HIV.
Thank you Dr. Young!