Harris M, Zalunardo N, Bonner S, Werb R, Valyi M, Montaner JS; Conference on Retroviruses and Opportunistic Infections (11th : 2004 : San Francisco, Calif.).
Program Abstr Conf Retrovir Oppor Infect 11th 2004 San Franc Calif. 2004 Feb 8-11; 11: abstract no. 750.
British Columbia Ctr. for Excellence in HIV/AIDS, Vancouver, Canada and 2St. Paul's Hosp., Vancouver, Canada
BACKGROUND: Tenofovir DF (TDF) is not recommended for patients with renal impairment, defined as creatinine (Cr) clearance <60 mL/min. Cr clearance is not routinely measured; hence serum Cr is commonly used. TDF-related nephrotoxicity has occurred in patients who had normal Cr before starting TDF. Therefore, we studied whether pre-TDF glomerular filtration rate (GFR) (estimated without 24-hr urine collection) in pts with TDF-related nephrotoxicity differed from the GFR of patients who took TDF without developing nephrotoxicity.METHODS: TDF was prescribed through an expanded access program starting December 2001. The present analysis included HIV+ adults who had serum Cr in the normal range (40 to 120 (mol/L) before starting TDF and who developed TDF-related renal toxicity, defined as clinically significant Cr increases on TDF with no other evident etiology, which resolved when TDF was discontinued. For each case, 2 gender-matched controls were randomly selected who started TDF in the same month and who remained on TDF with normal serum Cr as of September 2003. GFR was estimated using the modified MDRD formula of Levey et al.: 186 x Cr (mg/dL)-1.154 x age-0.203 x 1.212 if black x 0.742 if female (normal range for GFR 100-120 mL/min). The effect of pre-TDF baseline serum Cr and GFR were compared using logistic regression adjusting for the TDF start date.RESULTS: Twelve male patients stopped TDF after 5 to 18 months because their Cr level increased; 8/12 also had evidence of drug toxicity on renal biopsy. Mean baseline serum Cr in these 12 cases was 101 (mol/L (range 73 to 120). Despite normal Cr at baseline, all 12 cases had GFR below the normal range before starting TDF: mean 74 mL/min (range 58 to 98); 10/12 had GFR <80. The 24 male controls had mean baseline Cr of 76 (mol/L (range 54 to 96) and mean GFR 104 mL/min (range 80 to 152). Baseline GFR was <100 mL/min in 10/24 controls but <80 in none. Baseline Cr was higher in cases (p = 0.0035), though still within the normal range; the odds ratio (OR) for renal toxicity was 1.16 per (mol/L increase in Cr. Baseline GFR was lower in cases than in controls (p = 0.0084); OR for renal toxicity was 1.19 per mL/min decrease in GFR.CONCLUSIONS: Among male patients with serum Cr in the normal range, those with a reduced GFR, particularly those with GFR <80 mL/min appear to be at risk of developing nephrotoxicity on TDF. Our results suggest that a calculated estimate of GFR may be used prospectively to identify patients at risk for TDF-related nephrotoxicity.
Publication Types:
Keywords:
- Adenine
- Adult
- Case-Control Studies
- Chromium
- Chromium Radioisotopes
- Creatinine
- Female
- Glomerular Filtration Rate
- Humans
- Kidney Diseases
- Male
- Nephrosis
- Reference Values
- tenofovir
- utilization
Other ID:
UI: 102270939
From Meeting Abstracts