Clinical and genetic factors associated with kidney tubular dysfunction in a
real-life single centre cohort of HIV-positive patients
#MMPMID28583112
Salvaggio SE
; Giacomelli A
; Falvella FS
; Oreni ML
; Meraviglia P
; Atzori C
; Clementi EGI
; Galli M
; Rusconi S
BMC Infect Dis
2017[Jun]; 17
(1
): 396
PMID28583112
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BACKGROUND: Tenofovir (TDF) is one of the most widely used antiretroviral drug.
Despite the high degree of tolerability a small percentage of patients
experienced alteration in tubular function during TDF use. Intracellular TDF
disposition is regulated by ATP-binding cassette (ABC) drug efflux transporters
and, a reduced transport activity may be implicated in accumulation of TDF into
the cells. The aim of our study was to assess the major determinants of TDF
associated tubular dysfunction (KTD) in a real-life setting including the
usefulness of single-nucleotide polymorphisms (SNPs) mapping into ABCC2, ABCC4
and ABCC10 genes. METHODS: We retrospectively analyzed all HIV positive patients
who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University
of Milan from April 2013 to June 2016. All patients treated with TDF who
underwent a genotypization for the functional variants mapping in ABCC2 rs717620
(-24 C > T), ABCC4 rs1751034 (3463 A > G) and ABCC10 rs2125739 (T > C) were
evaluated. KTD was defined as the presence of urine phosphate wasting and/or
proteinuria at 24 h urine analysis. RESULTS: One hundred fifty-eight patients
were genotyped, of which 42 (26.6%) experienced signs of KTD. No statistical
significant differences were observed among patients with or without KTD
regarding age, gender, ethnicity and comorbidities (hypertension and diabetes).
The percentage of patients with KTD was higher among those with "GG" genotype at
rs1751034 of ABCC4 compared to patients without KTD [6 (14.3%) vs 4 (3.5%),
p = 0.01]. No statistical significant differences were observed regarding the
distribution of ABCC2 and ABCC10 SNPs. Carriers of "G" allele in homozygous
status at rs1751034 of ABCC4 showed a significant association with KTD (Odds
Ratio 4.67, 95% CI 1.25-17.46, p = 0.02) in bivariate analysis, but this
association was lost in multivariable analysis. A significant association between
bone diseases and KTD was observed (Odds Ratio 3.178, 95%CI 1.529-6.603,
p = 0.002). CONCLUSIONS: According to our results ABCC4 rs1751034 could be a
genetic determinant of KTD; however validation studies are needed for therapy
personalization. Noteworthy, a strong association between bone disease and KTD
was also observed.
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