title: Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana.
abstract: BACKGROUND
  HIV infection is associated with increased risk of renal dysfunction, including tubular dysfunction (TD) related to antiretroviral therapy (ART). Tenofovir disoproxil fumarate (TDF) is becoming available for ART in sub-Saharan Africa, although data on its long-term safety there is limited. We aimed to study the prevalence of HIV-associated renal dysfunction in Ghana and explore associations between proteinuria or TD and potential risk factors, including TDF use.
  
  
  METHODS
  A single-centre cross-sectional observational study of patients taking ART was undertaken. Creatinine clearance (CrCl) was calculated and proteinuria detected with dipsticks. Spot urinary albumin and protein:creatinine ratios (uACR/uPCR) were measured and further evidence of TD (defined as having two or more characteristic features) sought. Logistic regression analysis identified factors associated with proteinuria or TD.
  
  
  RESULTS
  In 330 patients, of whom 101 were taking TDF (median 20 months), the prevalence of CrCl < 60 ml/min/1.73 m(2), dipstick proteinuria and TD was 7 %, 37 % and 15 %. Factors associated with proteinuria were baseline CD4-count [aOR 0.86/100 cell increment (95 % CI, 0.74-0.99)] and TDF use [aOR 2.74 (95 % CI, 1.38-5.43)]. The only factor associated with TD was TDF use [aOR 3.43 (95 % CI, 1.10-10.69)]. In a subset with uPCR measurements, uPCRs were significantly higher in patients taking TDF than those on other drugs (10.8 vs. 5.7 mg/mmol, p < 0.001), and urinary albuin:protein ratios significantly lower (0.24 vs. 0.58, p < 0.001).
  
  
  CONCLUSIONS
  Both proteinuria and TD are common and associated with TDF use in Ghana. Further longitudinal studies to determine whether proteinuria, TD or TDF use are linked to progressive decline in renal function or other adverse outcomes are needed in Africa.
authors.affiliation: Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW, UK. davidr.chadwick@stees.nhs.uk.
authors.forename: David R
authors.initials: DR
authors.lastname: Chadwick
authors.affiliation: Kwame Nkrumah University of Science & Technology, Kumasi, Ghana. stephensarfo78@gmail.com.|Komfo Anokye Teaching Hospital, Kumasi, Ghana. stephensarfo78@gmail.com.
authors.forename: Fred S
authors.initials: FS
authors.lastname: Sarfo
authors.affiliation: Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW, UK. esmkirk@msn.com.
authors.forename: Elaine S M
authors.initials: ES
authors.lastname: Kirk
authors.affiliation: Kwame Nkrumah University of Science & Technology, Kumasi, Ghana. dokidinks@gmail.com.
authors.forename: Dorcas
authors.initials: D
authors.lastname: Owusu
authors.affiliation: Kwame Nkrumah University of Science & Technology, Kumasi, Ghana. gbeduaddo@gmail.com.|Komfo Anokye Teaching Hospital, Kumasi, Ghana. gbeduaddo@gmail.com.
authors.forename: George
authors.initials: G
authors.lastname: Bedu-Addo
authors.affiliation: Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW, UK. victoria.parris@stees.nhs.uk.
authors.forename: Victoria
authors.initials: V
authors.lastname: Parris
authors.affiliation: University of Leicester, Leicester, UK. l_owusu44@hotmail.com.
authors.forename: Ann Lorraine
authors.initials: AL
authors.lastname: Owusu
authors.affiliation: Kwame Nkrumah University of Science & Technology, Kumasi, Ghana. rodamephillips@gmail.com.|Komfo Anokye Teaching Hospital, Kumasi, Ghana. rodamephillips@gmail.com.
authors.forename: Richard
authors.initials: R
authors.lastname: Phillips
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D000998:Antiviral Agents; D015984:Causality; D015897:Comorbidity; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology; D005869:Ghana / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology; D015995:Prevalence; D011507:Proteinuria / Q000139:chemically induced / Q000453:epidemiology; D018570:Risk Assessment; D000068698:Tenofovir / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D000068698:Tenofovir