Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir

被引:249
作者
Labarga, Pablo [1 ]
Barreiro, Pablo [1 ]
Martin-Carbonero, Luz [1 ]
Rodriguez-Novoa, Sonia [2 ]
Solera, Carmen [1 ]
Medrano, Jose [1 ]
Rivas, Pablo [1 ]
Albalater, Marta [3 ]
Blanco, Francisco [1 ]
Moreno, Victoria [1 ]
Vispo, Eugenia [1 ]
Soriano, Vincent [1 ]
机构
[1] Hosp Carlos III, Dept Infect Dis, Madrid 28029, Spain
[2] Hosp Carlos III, Pharmacol Unit, Madrid 28029, Spain
[3] Fdn Jimenez Diaz, Dept Nephrol, E-28040 Madrid, Spain
关键词
bone; Fanconi syndrome; HIV; kidney; tenofovir; SINGLE NUCLEOTIDE POLYMORPHISMS; VIRUS-INFECTED PATIENTS; DISOPROXIL FUMARATE; FANCONI-SYNDROME; RENAL-FAILURE; EXPERIENCED PATIENTS; NEPHROTOXICITY; THERAPY; MANAGEMENT; SAFETY;
D O I
10.1097/QAD.0b013e3283262a64
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
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 beta 2-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 (CM 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. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
引用
收藏
页码:689 / 696
页数:8
相关论文
共 46 条
[1]
Tenofovir disoproxil fumarate, emtricitabine, and efavirenz compared with zidovudine/lamivudine and efavirenz in treatment-naive patients - 144-week analysis [J].
Arribas, Jose R. ;
Pozniak, Anton L. ;
Gallant, Joel E. ;
DeJesus, Edwin ;
Gazzard, Brian ;
Campo, Rafael E. ;
Chen, Shan-Shan ;
McColl, Damian ;
Holmes, Charles B. ;
Enejosa, Jeffrey ;
Toole, John J. ;
Cheng, Andrew K. .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2008, 47 (01) :74-78
[2]
HIV-associated nephropathy: epidemiology, pathogenesis, diagnosis and management [J].
Atta, Mohamed G. ;
Lucas, Gregory M. ;
Fine, Derek M. .
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, 2008, 6 (03) :365-371
[3]
Suboptimal CD4 gains in HIV-infected patients receiving didanosine plus tenofovir [J].
Barreiro, P ;
Soriano, V .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 57 (05) :806-809
[4]
Tenofovir-related nephrotoxicity in HIV-infected patients [J].
Barrios, A ;
García-Benayas, T ;
González-Lahoz, J ;
Soriano, V .
AIDS, 2004, 18 (06) :960-963
[5]
BELONGIA E, NIH CONSENS IN PRESS
[6]
Management of cardiovascular disease in patients with diabetes: the 2008 Canadian Diabetes Association guidelines [J].
Bhattacharyya, Onil K. ;
Shah, Baiju R. ;
Booth, Gillian L. .
CANADIAN MEDICAL ASSOCIATION JOURNAL, 2008, 179 (09) :920-926
[7]
Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6) [J].
Bleasby, K ;
Hall, LA ;
Perry, JL ;
Mohrenweiser, HW ;
Pritchard, JB .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 314 (02) :923-931
[8]
Tubulopathy consecutive to tenofovir-containing antiretroviral therapy in two patients infected with human immunodeficiency virus-1 [J].
Breton, G ;
Alexandre, M ;
Duval, X ;
Prie, D ;
Peytavin, G ;
Leport, C ;
Vildé, JL .
SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, 2004, 36 (6-7) :527-528
[9]
The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1 [J].
Cihlar, T ;
Lin, DC ;
Pritchard, JB ;
Fuller, MD ;
Mendel, DB ;
Sweet, DH .
MOLECULAR PHARMACOLOGY, 1999, 56 (03) :570-580
[10]
Fanconi's syndrome in HIV+ adults:: Report of three cases and literature review [J].
Earle, KE ;
Seneviratne, T ;
Shaker, J ;
Shoback, D .
JOURNAL OF BONE AND MINERAL RESEARCH, 2004, 19 (05) :714-721