Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir.
BACKGROUND
Tenofovir (TDF) is the most widely prescribed antiretroviral drug. Kidney abnormalities are the main concern using the drug. As glomerular function is infrequently 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 tubulopathy (glucosuria, hyperaminoaciduria, hyperphosphaturia, hyperuricosuria and beta2-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).


CONCLUSIONS
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.
Labarga
Pablo
P
Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
Barreiro
Pablo
P
Martin-Carbonero
Luz
L
Rodriguez-Novoa
Sonia
S
Solera
Carmen
C
Medrano
Jose
J
Rivas
Pablo
P
Albalater
Marta
M
Blanco
Francisco
F
Moreno
Victoria
V
Vispo
Eugenia
E
Soriano
Vincent
V
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D003404:Creatinine / Q000097:blood / Q000652:urine; D004812:Epidemiologic Methods; D005198:Fanconi Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007677:Kidney Function Tests / Q000379:methods; D007678:Kidney Glomerulus / Q000503:physiopathology*; D007684:Kidney Tubules / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine