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Kidney tubular abnormalities in the absence of
impaired glomerular function in HIV patients
treated with tenofovir
Pablo Labarga
a
, Pablo Barreiro
a
, Luz Martin-Carbonero
a
, Sonia
Rodriguez-Novoa
b
, Carmen Solera
a
, Jose Medrano
a
, Pablo Rivas
a
,
Marta Albalater
c
, Francisco Blanco
a
, Victoria Moreno
a
,
Eugenia Vispo
a
and Vincent Soriano
a
Background: Tenofovir (TDF) is the most widely prescribed antiretroviral drug. Kidney
abnormalities are the main concern using the drug. As glomerular function is infre-
quently affected in patients treated with TDF, herein, we report the results of an
extensive examination of tubular function.
Methods: Cross-sectional study of plasma and 24 h urine markers of kidney tubulo-
pathy (glucosuria, hyperaminoaciduria, hyperphosphaturia, hyperuricosuria and
b2-microglobulinuria) could be allocated in three groups: patients under a TDF-
containing HAART; patients on HAART never exposed to TDF; and antiretroviral-
naive individuals. Significant tubular damage was defined when at least two of these
parameters were repeatedly present, being at least one part of the Fanconi syndrome
criteria (glucosuria, hyperaminoaciduria and hyperphosphaturia). Glomerular function
was assessed using creatinine clearance.
Results: A total of 284 consecutive HIV patients were examined, 154 on TDF, 49 on other
HAART regimens and 81 drug-naive. No significant differences in creatinine clearance
were observed when comparing distinct groups. The proportion of patients with tubular
damage in groups 1, 2 and 3 were 22, 6 and 12%, respectively. In a multivariate analysis
[odds ratio (OR) {95% confidence interval (CI)} P], the only independent predictors of
tubular dysfunction were TDF use (21.6, 4.1–113, <0.001) and older age (1.1 per year,
1.0–1.1, 0.01).
Conclusion: Exposure to TDF is associated with an increased risk over time of kidney
tubular abnormalities in the absence of significant impaired glomerular function.
Although long-term consequences of this tubulopathy are unknown, close monitoring
of accelerated bone mineral loss and renal insufficiency are warranted. Periodic screening
of tubular function parameters should be recommended to patients receiving TDF.
ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
AIDS 2009, 23:689–696
Keywords: bone, Fanconi syndrome, HIV, kidney, tenofovir
Introduction
Tenofovir disoproxil fumarate (TDF) (Viread; Gilead
Sciences, San Francisco, California, USA) is the first
nucleotide reverse transcriptase inhibitor licensed for
the treatment of HIV infection [1]. The drug is also
active against hepatitis B virus (HBV), and recently it has
granted approval for this indication [2]. Given its
a
Infectious Diseases Department,
b
Pharmacology Unit, Hospital Carlos III, Madrid, and
c
Nephrology Department, Fundacio ´n
Jimenez Diaz, Madrid, Spain.
Correspondence to Dr Vincent Soriano, Department of Infectious Diseases, Hospital Carlos III, Calle Sinesio Delgado 10, Madrid
28029, Spain.
Tel: +34 91 4532500; fax: + 34 91 7336614; e-mail: vsoriano@dragonet.es
Received: 12 September 2008; revised: 15 November 2008; accepted: 11 December 2008.
DOI:10.1097/QAD.0b013e3283262a64
ISSN 0269-9370 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
689