Response to Blaas et al., ‘Acute renal failure in HIV patients with liver cirrhosis receiving tenofovir: a report of two cases’
Ranneberg, Britta; Mertenskoetter, Thomas; Pearce, Gill
Gilead Sciences, Martinsried, Germany.
Received 21 November, 2006
Accepted 28 November, 2006
The two case reports by Blaas et al.  underline the necessity of close monitoring for patients at possible increased risk of renal complications when receiving tenofovir disoproxil fumarate (TDF) as part of their antiretroviral therapy (ART). Unfortunately, some key information relevant to these cases that would be helpful for clinicians is missing in the publication. To assess the risk of developing renal complications in these two patients, knowledge of the baseline serum creatinine and estimated glomerular filtration rate before TDF therapy, as well as any dose interval adjustments, would have been helpful. In addition, it is not clear from the report whether the didanosine dosage was reduced.
In the current TDF summary of product characteristics , an evaluation of renal function at baseline and regular monitoring are recommended for all patients receiving TDF. More careful monitoring for signs of toxicity, such as deterioration of renal function, is recommended for patients with pre-existing renal impairment receiving the adjusted TDF dosage.
In patient 2, an unadjusted didanosine dosage (400 mg/day) might have contributed to the observed changes in renal function. It has been hypothesized that the increased plasma levels of didanosine resulting from the interaction between didanosine and TDF  may be relevant for alterations in renal function . The concurrent use of 400 mg didanosine and TDF was associated with lower mitochondrial DNA content, a finding not seen when TDF was used without didanosine. According to the current SmPC, the combination of TDF and didanosine is not recommended.
Both patients had very advanced HIV infection, along with risk factors previously described as being associated with renal complications in large cohorts [5,6]. For example, a low CD4 cell count, volume depletion, advanced disease and low weight were present in both of these cases. Serum creatinine might not be the best parameter to detect an alteration of renal function; in patients with low weight, an estimate of creatinine clearance has been shown to be a more accurate marker .
Blaas et al.  state that ‘the risk of renal failure in TDF-treated patients with liver cirrhosis is of particular importance for patients infected with HBV’. To draw this conclusion from two case reports might perhaps be premature, especially as the patients described had multiple risk factors for renal dysfunction. Another cohort  has previously reported a possible relationship between liver failure leading to hepatorenal syndrome and the subsequent impairment of renal function. Many other cohorts evaluating the use of TDF in patients with hepatitis B virus, both monoinfected and co-infected, show no increased risk of renal complications in patients with liver disease [9–11].
In conclusion, we would like to stress the importance of regular monitoring of renal function in patients with HIV before initiating ART and during therapy. For most approved nucleoside reverse transcriptase inhibitors, dosage or dose interval adjustments are necessary in patients with impaired renal function; therefore a determination of creatinine clearance at baseline should be a routine measure before the initiation of ART.
1. Blaas S, Schneidewind A, Glück T, Salzberger B. Acute renal failure in HIV patients with liver cirrhosis receiving tenofovir: a report of two cases. AIDS 2006; 20:1786–1787.
2. Viread SmPC for the European Union. Martinsried, Germany: Gilead Sciences; February 2006.
3. Ray AS, Olson L, Fridland A. Role of purine nucleoside phosphorylase in interactions between 2′,3′-dideoxyinosine and allopurinol, ganciclovir, or tenofovir. Antimicrob Agents Chemother 2004; 48:1089–1095.
4. Cote HCF, Magil AB, Harris M, Scarth BJ, Gadawski I, Wang N, et al
. Exploring mitochondrial nephrotoxicity as a potential mechanism of kidney dysfunction among HIV-infected patients on highly active antiretroviral therapy. Antiviral Ther 2006; 11:79–86.
5. Nelson M, Cooper D, Schooley R, Katlama C, Montaner J, Curtis S, et al
. The safety of tenofovir DF for the treatment of HIV infection: the first 4 years
. Paper presented at: 13th Conference on Retroviruses and Opportunistic Infections
. Denver, CO, 5–9 February 2006 [Poster 781].
6. Gallant JE, Parish M, Keruly J, Moore R. Changes in renal function in patients treated with tenofovir DF (TDF) compared to nucleoside reverse transcriptase inhibitors (NRTIs)
. Paper presented at: 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment
. Rio de Janeiro, Brazil, 24–27 July 2005 [poster TuPe2.3C18].
7. Peyriere H, Reynes J, Rouanet I, Daniel N, Merle de Boever C, Mauboussin JM, et al
. Renal tubular dysfunction associated with tenofovir therapy. J Acquir Immune Defic Syndr 2004; 35:269–273.
8. Jones R, Stebbing J, Nelson M, Moyle G, Bower M, Mandalia S, et al
. Renal dysfunction with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy regimens is not observed more frequently. J Acquir Immune Defic Syndr 2004; 37:1489–1495.
9. Schmutz G, Nelson M, Lutz T, Sheldon J, Bruno R, von Boemmel F, et al
. Combination of tenofovir and lamivudine versus tenofovir after lamivudine failure for therapy of hepatitis B in HIV-coinfection. AIDS 2006; 20:1951–1954.
10. Nunez M, Ramos B, Diaz-Pollan B, Camino N, Martin-Carbonero L, Barreiro P, et al
. Virological outcome of chronic hepatitis B virus infection in HIV-coinfected patients receiving anti-HBV active antiretroviral therapy. AIDS Res Hum Retroviruses 2006; 22:842–848.
11. Van Bommel F, Zollner B, Sarrazin C, Spengler U, Huppe D, Moller B, et al
. Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy. Hepatology 2006; 44:318–325.
© 2007 Lippincott Williams & Wilkins, Inc.
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