Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana
Identifieur interne : 000104 ( Pmc/Corpus ); précédent : 000103; suivant : 000105Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana
Auteurs : David R. Chadwick ; Fred S. Sarfo ; Elaine S. M. Kirk ; Dorcas Owusu ; George Bedu-Addo ; Victoria Parris ; Ann Lorraine Owusu ; Richard PhillipsSource :
- BMC Nephrology [ 1471-2369 ] ; 2015.
Abstract
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.
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.
In 330 patients, of whom 101 were taking TDF (median 20 months), the prevalence of CrCl < 60ml/min/1.73m2, 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
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.
Url:
DOI: 10.1186/s12882-015-0192-4
PubMed: 26627687
PubMed Central: 4666076
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PMC:4666076Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana</title><author><name sortKey="Chadwick, David R" sort="Chadwick, David R" uniqKey="Chadwick D" first="David R." last="Chadwick">David R. Chadwick</name><affiliation><nlm:aff id="Aff1">Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW UK</nlm:aff></affiliation></author><author><name sortKey="Sarfo, Fred S" sort="Sarfo, Fred S" uniqKey="Sarfo F" first="Fred S." last="Sarfo">Fred S. Sarfo</name><affiliation><nlm:aff id="Aff2">Kwame Nkrumah University of Science & Technology, Kumasi, Ghana</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3">Komfo Anokye Teaching Hospital, Kumasi, Ghana</nlm:aff></affiliation></author><author><name sortKey="Kirk, Elaine S M" sort="Kirk, Elaine S M" uniqKey="Kirk E" first="Elaine S. M." last="Kirk">Elaine S. M. Kirk</name><affiliation><nlm:aff id="Aff1">Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW UK</nlm:aff></affiliation></author><author><name sortKey="Owusu, Dorcas" sort="Owusu, Dorcas" uniqKey="Owusu D" first="Dorcas" last="Owusu">Dorcas Owusu</name><affiliation><nlm:aff id="Aff2">Kwame Nkrumah University of Science & Technology, Kumasi, Ghana</nlm:aff></affiliation></author><author><name sortKey="Bedu Addo, George" sort="Bedu Addo, George" uniqKey="Bedu Addo G" first="George" last="Bedu-Addo">George Bedu-Addo</name><affiliation><nlm:aff id="Aff2">Kwame Nkrumah University of Science & Technology, Kumasi, Ghana</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3">Komfo Anokye Teaching Hospital, Kumasi, Ghana</nlm:aff></affiliation></author><author><name sortKey="Parris, Victoria" sort="Parris, Victoria" uniqKey="Parris V" first="Victoria" last="Parris">Victoria Parris</name><affiliation><nlm:aff id="Aff1">Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW UK</nlm:aff></affiliation></author><author><name sortKey="Owusu, Ann Lorraine" sort="Owusu, Ann Lorraine" uniqKey="Owusu A" first="Ann Lorraine" last="Owusu">Ann Lorraine Owusu</name><affiliation><nlm:aff id="Aff4">University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Phillips, Richard" sort="Phillips, Richard" uniqKey="Phillips R" first="Richard" last="Phillips">Richard Phillips</name><affiliation><nlm:aff id="Aff2">Kwame Nkrumah University of Science & Technology, Kumasi, Ghana</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3">Komfo Anokye Teaching Hospital, Kumasi, Ghana</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26627687</idno><idno type="pmc">4666076</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666076</idno><idno type="RBID">PMC:4666076</idno><idno type="doi">10.1186/s12882-015-0192-4</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000104</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000104</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana</title><author><name sortKey="Chadwick, David R" sort="Chadwick, David R" uniqKey="Chadwick D" first="David R." last="Chadwick">David R. Chadwick</name><affiliation><nlm:aff id="Aff1">Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW UK</nlm:aff></affiliation></author><author><name sortKey="Sarfo, Fred S" sort="Sarfo, Fred S" uniqKey="Sarfo F" first="Fred S." last="Sarfo">Fred S. Sarfo</name><affiliation><nlm:aff id="Aff2">Kwame Nkrumah University of Science & Technology, Kumasi, Ghana</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3">Komfo Anokye Teaching Hospital, Kumasi, Ghana</nlm:aff></affiliation></author><author><name sortKey="Kirk, Elaine S M" sort="Kirk, Elaine S M" uniqKey="Kirk E" first="Elaine S. M." last="Kirk">Elaine S. M. Kirk</name><affiliation><nlm:aff id="Aff1">Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW UK</nlm:aff></affiliation></author><author><name sortKey="Owusu, Dorcas" sort="Owusu, Dorcas" uniqKey="Owusu D" first="Dorcas" last="Owusu">Dorcas Owusu</name><affiliation><nlm:aff id="Aff2">Kwame Nkrumah University of Science & Technology, Kumasi, Ghana</nlm:aff></affiliation></author><author><name sortKey="Bedu Addo, George" sort="Bedu Addo, George" uniqKey="Bedu Addo G" first="George" last="Bedu-Addo">George Bedu-Addo</name><affiliation><nlm:aff id="Aff2">Kwame Nkrumah University of Science & Technology, Kumasi, Ghana</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3">Komfo Anokye Teaching Hospital, Kumasi, Ghana</nlm:aff></affiliation></author><author><name sortKey="Parris, Victoria" sort="Parris, Victoria" uniqKey="Parris V" first="Victoria" last="Parris">Victoria Parris</name><affiliation><nlm:aff id="Aff1">Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW UK</nlm:aff></affiliation></author><author><name sortKey="Owusu, Ann Lorraine" sort="Owusu, Ann Lorraine" uniqKey="Owusu A" first="Ann Lorraine" last="Owusu">Ann Lorraine Owusu</name><affiliation><nlm:aff id="Aff4">University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Phillips, Richard" sort="Phillips, Richard" uniqKey="Phillips R" first="Richard" last="Phillips">Richard Phillips</name><affiliation><nlm:aff id="Aff2">Kwame Nkrumah University of Science & Technology, Kumasi, Ghana</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3">Komfo Anokye Teaching Hospital, Kumasi, Ghana</nlm:aff></affiliation></author></analytic><series><title level="j">BMC Nephrology</title><idno type="eISSN">1471-2369</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>In 330 patients, of whom 101 were taking TDF (median 20 months), the prevalence of CrCl < 60ml/min/1.73m<sup>2</sup>, 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 <italic>vs.</italic> 5.7 mg/mmol, <italic>p</italic> < 0.001), and urinary albuin:protein ratios significantly lower (0.24 <italic>vs.</italic> 0.58, <italic>p</italic> < 0.001).</p></sec><sec><title>Conclusions</title><p>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.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Szczech, La" uniqKey="Szczech L">LA Szczech</name></author><author><name sortKey="Gange, Sj" uniqKey="Gange S">SJ Gange</name></author><author><name sortKey="Van Der Horst, C" uniqKey="Van Der Horst C">C van der Horst</name></author><author><name sortKey="Bartlett, Ja" uniqKey="Bartlett J">JA Bartlett</name></author><author><name sortKey="Young, M" uniqKey="Young M">M Young</name></author><author><name sortKey="Cohen, Mh" uniqKey="Cohen M">MH Cohen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mocroft, A" uniqKey="Mocroft A">A Mocroft</name></author><author><name sortKey="Kirk, O" uniqKey="Kirk O">O Kirk</name></author><author><name sortKey="Reiss, P" uniqKey="Reiss P">P Reiss</name></author><author><name sortKey="De Wit, S" uniqKey="De Wit S">S De Wit</name></author><author><name sortKey="Sedlacek, D" uniqKey="Sedlacek D">D Sedlacek</name></author><author><name sortKey="Beniowski, M" uniqKey="Beniowski M">M Beniowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Daar, Es" uniqKey="Daar E">ES Daar</name></author><author><name sortKey="Tierney, C" uniqKey="Tierney C">C Tierney</name></author><author><name sortKey="Fischl, Ma" uniqKey="Fischl M">MA Fischl</name></author><author><name sortKey="Sax, Pe" uniqKey="Sax P">PE Sax</name></author><author><name sortKey="Mollan, K" uniqKey="Mollan K">K Mollan</name></author><author><name sortKey="Budhathoki, C" uniqKey="Budhathoki C">C Budhathoki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Campbell, Lj" uniqKey="Campbell L">LJ Campbell</name></author><author><name sortKey="Ibrahim, F" uniqKey="Ibrahim F">F Ibrahim</name></author><author><name sortKey="Fisher, M" uniqKey="Fisher M">M Fisher</name></author><author><name sortKey="Holt, Sg" uniqKey="Holt S">SG Holt</name></author><author><name sortKey="Hendry, Bm" uniqKey="Hendry B">BM Hendry</name></author><author><name sortKey="Post, Fa" uniqKey="Post F">FA Post</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lucas, Gm" uniqKey="Lucas G">GM Lucas</name></author><author><name sortKey="Eustace, Ja" uniqKey="Eustace J">JA Eustace</name></author><author><name sortKey="Sozio, S" uniqKey="Sozio S">S Sozio</name></author><author><name sortKey="Mentari, Ek" uniqKey="Mentari E">EK Mentari</name></author><author><name sortKey="Appiah, Ka" uniqKey="Appiah K">KA Appiah</name></author><author><name sortKey="Moore, Rd" uniqKey="Moore R">RD Moore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Atta, Mg" uniqKey="Atta M">MG Atta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reid, A" uniqKey="Reid A">A Reid</name></author><author><name sortKey="Stohr, W" uniqKey="Stohr W">W Stöhr</name></author><author><name sortKey="Walker, As" uniqKey="Walker A">AS Walker</name></author><author><name sortKey="Williams, Ig" uniqKey="Williams I">IG Williams</name></author><author><name sortKey="Kityo, C" uniqKey="Kityo C">C Kityo</name></author><author><name sortKey="Hughes, P" uniqKey="Hughes P">P Hughes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gupta, Sk" uniqKey="Gupta S">SK Gupta</name></author><author><name sortKey="Parker, Ra" uniqKey="Parker R">RA Parker</name></author><author><name sortKey="Robbins, Gk" uniqKey="Robbins G">GK Robbins</name></author><author><name sortKey="Dube, Mp" uniqKey="Dube M">MP Dubé</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kopp, Jb" uniqKey="Kopp J">JB Kopp</name></author><author><name sortKey="Winkler, C" uniqKey="Winkler C">C Winkler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rostand, Sg" uniqKey="Rostand S">SG Rostand</name></author><author><name sortKey="Kirk, Ka" uniqKey="Kirk K">KA Kirk</name></author><author><name sortKey="Rutsky, Ea" uniqKey="Rutsky E">EA Rutsky</name></author><author><name sortKey="Pate, Ba" uniqKey="Pate B">BA Pate</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klag, Mj" uniqKey="Klag M">MJ Klag</name></author><author><name sortKey="Whelton, Pk" uniqKey="Whelton P">PK Whelton</name></author><author><name sortKey="Randall, Bl" uniqKey="Randall B">BL Randall</name></author><author><name sortKey="Neaton, Jd" uniqKey="Neaton J">JD Neaton</name></author><author><name sortKey="Brancati, Fl" uniqKey="Brancati F">FL Brancati</name></author><author><name sortKey="Stamler, J" uniqKey="Stamler J">J Stamler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Padulles, A" uniqKey="Padulles A">A Padullés</name></author><author><name sortKey="Rama, I" uniqKey="Rama I">I Rama</name></author><author><name sortKey="Llaudo, I" uniqKey="Llaudo I">I Llaudo</name></author><author><name sortKey="Lloberas, N" uniqKey="Lloberas N">N Lloberas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okafor, Uh" uniqKey="Okafor U">UH Okafor</name></author><author><name sortKey="Unuigbe, Ei" uniqKey="Unuigbe E">EI Unuigbe</name></author><author><name sortKey="Ojogwu, Li" uniqKey="Ojogwu L">LI Ojogwu</name></author><author><name sortKey="Oviasu, E" uniqKey="Oviasu E">E Oviasu</name></author><author><name sortKey="Wokoma, Fs" uniqKey="Wokoma F">FS Wokoma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fabian, J" uniqKey="Fabian J">J Fabian</name></author><author><name sortKey="Naicker, S" uniqKey="Naicker S">S Naicker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wools Kaloustian, K" uniqKey="Wools Kaloustian K">K Wools-Kaloustian</name></author><author><name sortKey="Gupta, Sk" uniqKey="Gupta S">SK Gupta</name></author><author><name sortKey="Muloma, E" uniqKey="Muloma E">E Muloma</name></author><author><name sortKey="Owino Ong Or, W" uniqKey="Owino Ong Or W">W Owino-Ong'or</name></author><author><name sortKey="Sidle, J" uniqKey="Sidle J">J Sidle</name></author><author><name sortKey="Aubrey, Rw" uniqKey="Aubrey R">RW Aubrey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sarfo, Fs" uniqKey="Sarfo F">FS Sarfo</name></author><author><name sortKey="Keegan, R" uniqKey="Keegan R">R Keegan</name></author><author><name sortKey="Appiah, L" uniqKey="Appiah L">L Appiah</name></author><author><name sortKey="Shakoor, S" uniqKey="Shakoor S">S Shakoor</name></author><author><name sortKey="Phillips, R" uniqKey="Phillips R">R Phillips</name></author><author><name sortKey="Norman, B" uniqKey="Norman B">B Norman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Han, Tm" uniqKey="Han T">TM Han</name></author><author><name sortKey="Naicker, S" uniqKey="Naicker S">S Naicker</name></author><author><name sortKey="Ramdial, Pk" uniqKey="Ramdial P">PK Ramdial</name></author><author><name sortKey="Assounga, Ag" uniqKey="Assounga A">AG Assounga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mulenga, Lb" uniqKey="Mulenga L">LB Mulenga</name></author><author><name sortKey="Kruse, G" uniqKey="Kruse G">G Kruse</name></author><author><name sortKey="Lakhi, S" uniqKey="Lakhi S">S Lakhi</name></author><author><name sortKey="Cantrell, Ra" uniqKey="Cantrell R">RA Cantrell</name></author><author><name sortKey="Reid, Se" uniqKey="Reid S">SE Reid</name></author><author><name sortKey="Zulu, I" uniqKey="Zulu I">I Zulu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jao, J" uniqKey="Jao J">J Jao</name></author><author><name sortKey="Lo, W" uniqKey="Lo W">W Lo</name></author><author><name sortKey="Toro, Pl" uniqKey="Toro P">PL Toro</name></author><author><name sortKey="Wyatt, C" uniqKey="Wyatt C">C Wyatt</name></author><author><name sortKey="Palmer, D" uniqKey="Palmer D">D Palmer</name></author><author><name sortKey="Abrams, Ej" uniqKey="Abrams E">EJ Abrams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodriguez N Voa, S" uniqKey="Rodriguez N Voa S">S Rodriguez-Nóvoa</name></author><author><name sortKey="Labarga, P" uniqKey="Labarga P">P Labarga</name></author><author><name sortKey="Soriano, V" uniqKey="Soriano V">V Soriano</name></author><author><name sortKey="Egan, D" uniqKey="Egan D">D Egan</name></author><author><name sortKey="Albalater, M" uniqKey="Albalater M">M Albalater</name></author><author><name sortKey="Morello, J" uniqKey="Morello J">J Morello</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Squires, K" uniqKey="Squires K">K Squires</name></author><author><name sortKey="Pozniak, Al" uniqKey="Pozniak A">AL Pozniak</name></author><author><name sortKey="Pierone, G" uniqKey="Pierone G">G Pierone</name></author><author><name sortKey="Steinhart, Cr" uniqKey="Steinhart C">CR Steinhart</name></author><author><name sortKey="Berger, D" uniqKey="Berger D">D Berger</name></author><author><name sortKey="Bellos, Nc" uniqKey="Bellos N">NC Bellos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gallant, Je" uniqKey="Gallant J">JE Gallant</name></author><author><name sortKey="Staszewski, S" uniqKey="Staszewski S">S Staszewski</name></author><author><name sortKey="Pozniak, Al" uniqKey="Pozniak A">AL Pozniak</name></author><author><name sortKey="Dejesus, E" uniqKey="Dejesus E">E DeJesus</name></author><author><name sortKey="Suleiman, Jm" uniqKey="Suleiman J">JM Suleiman</name></author><author><name sortKey="Miller, Md" uniqKey="Miller M">MD Miller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quimby, D" uniqKey="Quimby D">D Quimby</name></author><author><name sortKey="Brito, Mo" uniqKey="Brito M">MO Brito</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malik, A" uniqKey="Malik A">A Malik</name></author><author><name sortKey="Abraham, P" uniqKey="Abraham P">P Abraham</name></author><author><name sortKey="Malik, N" uniqKey="Malik N">N Malik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Young, B" uniqKey="Young B">B Young</name></author><author><name sortKey="Buchacz, K" uniqKey="Buchacz K">K Buchacz</name></author><author><name sortKey="Baker, Rk" uniqKey="Baker R">RK Baker</name></author><author><name sortKey="Moorman, Ac" uniqKey="Moorman A">AC Moorman</name></author><author><name sortKey="Wood, Kc" uniqKey="Wood K">KC Wood</name></author><author><name sortKey="Chmiel, J" uniqKey="Chmiel J">J Chmiel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Solomon, Mm" uniqKey="Solomon M">MM Solomon</name></author><author><name sortKey="Lama, Jr" uniqKey="Lama J">JR Lama</name></author><author><name sortKey="Glidden, Dv" uniqKey="Glidden D">DV Glidden</name></author><author><name sortKey="Mulligan, K" uniqKey="Mulligan K">K Mulligan</name></author><author><name sortKey="Mcmahan, V" uniqKey="Mcmahan V">V McMahan</name></author><author><name sortKey="Liu, Ay" uniqKey="Liu A">AY Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Purswani, M" uniqKey="Purswani M">M Purswani</name></author><author><name sortKey="Patel, K" uniqKey="Patel K">K Patel</name></author><author><name sortKey="Kopp, Jb" uniqKey="Kopp J">JB Kopp</name></author><author><name sortKey="Seage, Gr" uniqKey="Seage G">GR Seage</name></author><author><name sortKey="Chernoff, Mc" uniqKey="Chernoff M">MC Chernoff</name></author><author><name sortKey="Hazra, R" uniqKey="Hazra R">R Hazra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reynes, J" uniqKey="Reynes J">J Reynes</name></author><author><name sortKey="Cournil, A" uniqKey="Cournil A">A Cournil</name></author><author><name sortKey="Peyriere, H" uniqKey="Peyriere H">H Peyriere</name></author><author><name sortKey="Psomas, C" uniqKey="Psomas C">C Psomas</name></author><author><name sortKey="Guiller, E" uniqKey="Guiller E">E Guiller</name></author><author><name sortKey="Chatron, M" uniqKey="Chatron M">M Chatron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dauchy, Fa" uniqKey="Dauchy F">FA Dauchy</name></author><author><name sortKey="Lawson Ayayi, S" uniqKey="Lawson Ayayi S">S Lawson-Ayayi</name></author><author><name sortKey="De La Faille, R" uniqKey="De La Faille R">R de La Faille</name></author><author><name sortKey="Bonnet, F" uniqKey="Bonnet F">F Bonnet</name></author><author><name sortKey="Rigothier, C" uniqKey="Rigothier C">C Rigothier</name></author><author><name sortKey="Mehsen, N" uniqKey="Mehsen N">N Mehsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Labarga, P" uniqKey="Labarga P">P Labarga</name></author><author><name sortKey="Barreiro, P" uniqKey="Barreiro P">P Barreiro</name></author><author><name sortKey="Martin Carbonero, L" uniqKey="Martin Carbonero L">L Martin-Carbonero</name></author><author><name sortKey="Rodriguez Novoa, S" uniqKey="Rodriguez Novoa S">S Rodriguez-Novoa</name></author><author><name sortKey="Solera, C" uniqKey="Solera C">C Solera</name></author><author><name sortKey="Medrano, J" uniqKey="Medrano J">J Medrano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stohr, W" uniqKey="Stohr W">W Stöhr</name></author><author><name sortKey="Reid, A" uniqKey="Reid A">A Reid</name></author><author><name sortKey="Walker, As" uniqKey="Walker A">AS Walker</name></author><author><name sortKey="Ssali, F" uniqKey="Ssali F">F Ssali</name></author><author><name sortKey="Munderi, P" uniqKey="Munderi P">P Munderi</name></author><author><name sortKey="Mambule, I" uniqKey="Mambule I">I Mambule</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mulenga, L" uniqKey="Mulenga L">L Mulenga</name></author><author><name sortKey="Musonda, P" uniqKey="Musonda P">P Musonda</name></author><author><name sortKey="Mwango, A" uniqKey="Mwango A">A Mwango</name></author><author><name sortKey="Vinikoor, Mj" uniqKey="Vinikoor M">MJ Vinikoor</name></author><author><name sortKey="Davies, Ma" uniqKey="Davies M">MA Davies</name></author><author><name sortKey="Mweemba, A" uniqKey="Mweemba A">A Mweemba</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Geretti, Am" uniqKey="Geretti A">AM Geretti</name></author><author><name sortKey="Patel, M" uniqKey="Patel M">M Patel</name></author><author><name sortKey="Sarfo, Fs" uniqKey="Sarfo F">FS Sarfo</name></author><author><name sortKey="Chadwick, D" uniqKey="Chadwick D">D Chadwick</name></author><author><name sortKey="Verheyen, J" uniqKey="Verheyen J">J Verheyen</name></author><author><name sortKey="Fraune, M" uniqKey="Fraune M">M Fraune</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mocroft, A" uniqKey="Mocroft A">A Mocroft</name></author><author><name sortKey="Neuhaus, J" uniqKey="Neuhaus J">J Neuhaus</name></author><author><name sortKey="Peters, L" uniqKey="Peters L">L Peters</name></author><author><name sortKey="Ryom, L" uniqKey="Ryom L">L Ryom</name></author><author><name sortKey="Bickel, M" uniqKey="Bickel M">M Bickel</name></author><author><name sortKey="Grint, D" uniqKey="Grint D">D Grint</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Del Palacio, M" uniqKey="Del Palacio M">M Del Palacio</name></author><author><name sortKey="Romero, S" uniqKey="Romero S">S Romero</name></author><author><name sortKey="Casado, Jl" uniqKey="Casado J">JL Casado</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Msango, L" uniqKey="Msango L">L Msango</name></author><author><name sortKey="Downs, Ja" uniqKey="Downs J">JA Downs</name></author><author><name sortKey="Kalluvva, Se" uniqKey="Kalluvva S">SE Kalluvva</name></author><author><name sortKey="Kidenya, Br" uniqKey="Kidenya B">BR Kidenya</name></author><author><name sortKey="Kabangila, R" uniqKey="Kabangila R">R Kabangila</name></author><author><name sortKey="Johnson, Wd" uniqKey="Johnson W">WD Johnson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sise, Me" uniqKey="Sise M">ME Sise</name></author><author><name sortKey="Hirsch, Js" uniqKey="Hirsch J">JS Hirsch</name></author><author><name sortKey="Canetta, Pa" uniqKey="Canetta P">PA Canetta</name></author><author><name sortKey="Herlitz, L" uniqKey="Herlitz L">L Herlitz</name></author><author><name sortKey="Mohan, S" uniqKey="Mohan S">S Mohan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mills, A" uniqKey="Mills A">A Mills</name></author><author><name sortKey="Crofoot, G" uniqKey="Crofoot G">G Crofoot</name></author><author><name sortKey="Mcdonald, C" uniqKey="Mcdonald C">C McDonald</name></author><author><name sortKey="Shalit, P" uniqKey="Shalit P">P Shalit</name></author><author><name sortKey="Flamm, Ja" uniqKey="Flamm J">JA Flamm</name></author><author><name sortKey="Gathe, J" uniqKey="Gathe J">J Gathe</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Nephrol</journal-id><journal-id journal-id-type="iso-abbrev">BMC Nephrol</journal-id><journal-title-group><journal-title>BMC Nephrology</journal-title></journal-title-group><issn pub-type="epub">1471-2369</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26627687</article-id><article-id pub-id-type="pmc">4666076</article-id><article-id pub-id-type="publisher-id">192</article-id><article-id pub-id-type="doi">10.1186/s12882-015-0192-4</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Chadwick</surname><given-names>David R.</given-names></name><address><phone>44 1642 854429</phone><email>davidr.chadwick@stees.nhs.uk</email></address><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Sarfo</surname><given-names>Fred S.</given-names></name><address><email>stephensarfo78@gmail.com</email></address><xref ref-type="aff" rid="Aff2"></xref><xref ref-type="aff" rid="Aff3"></xref></contrib><contrib contrib-type="author"><name><surname>Kirk</surname><given-names>Elaine S. M.</given-names></name><address><email>esmkirk@msn.com</email></address><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Owusu</surname><given-names>Dorcas</given-names></name><address><email>dokidinks@gmail.com</email></address><xref ref-type="aff" rid="Aff2"></xref></contrib><contrib contrib-type="author"><name><surname>Bedu-Addo</surname><given-names>George</given-names></name><address><email>gbeduaddo@gmail.com</email></address><xref ref-type="aff" rid="Aff2"></xref><xref ref-type="aff" rid="Aff3"></xref></contrib><contrib contrib-type="author"><name><surname>Parris</surname><given-names>Victoria</given-names></name><address><email>victoria.parris@stees.nhs.uk</email></address><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Owusu</surname><given-names>Ann Lorraine</given-names></name><address><email>l_owusu44@hotmail.com</email></address><xref ref-type="aff" rid="Aff4"></xref></contrib><contrib contrib-type="author"><name><surname>Phillips</surname><given-names>Richard</given-names></name><address><email>rodamephillips@gmail.com</email></address><xref ref-type="aff" rid="Aff2"></xref><xref ref-type="aff" rid="Aff3"></xref></contrib><aff id="Aff1"><label></label>Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, TS4 3BW UK</aff><aff id="Aff2"><label></label>Kwame Nkrumah University of Science & Technology, Kumasi, Ghana</aff><aff id="Aff3"><label></label>Komfo Anokye Teaching Hospital, Kumasi, Ghana</aff><aff id="Aff4"><label></label>University of Leicester, Leicester, UK</aff></contrib-group><pub-date pub-type="epub"><day>1</day><month>12</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>12</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2015</year></pub-date><volume>16</volume><elocation-id>195</elocation-id><history><date date-type="received"><day>24</day><month>6</month><year>2015</year></date><date date-type="accepted"><day>24</day><month>11</month><year>2015</year></date></history><permissions><copyright-statement>© Chadwick et al. 2015</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>In 330 patients, of whom 101 were taking TDF (median 20 months), the prevalence of CrCl < 60ml/min/1.73m<sup>2</sup>, 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 <italic>vs.</italic> 5.7 mg/mmol, <italic>p</italic> < 0.001), and urinary albuin:protein ratios significantly lower (0.24 <italic>vs.</italic> 0.58, <italic>p</italic> < 0.001).</p></sec><sec><title>Conclusions</title><p>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.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>HIV</kwd><kwd>Kidney</kwd><kwd>Renal</kwd><kwd>TDF</kwd><kwd>Tubular</kwd><kwd>Africa</kwd><kwd>Antiretroviral therapy</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2015</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="Sec1" sec-type="introduction"><title>Background</title><p>HIV-infected individuals are at increased risk of renal dysfunction due to a number of causes including HIV-associated nephropathy (HIVAN), HIV immune complex glomerulonephritis and antiretroviral therapy (ART) [<xref ref-type="bibr" rid="CR1">1</xref>–<xref ref-type="bibr" rid="CR4">4</xref>]. The use of ART has decreased HIV-associated renal dysfunction and progression to end stage renal disease (ESRD) [<xref ref-type="bibr" rid="CR5">5</xref>–<xref ref-type="bibr" rid="CR8">8</xref>], but renal dysfunction remains common amongst HIV-infected patients. There is a higher prevalence of renal dysfunction and ESRD among the African-American population (largely of West African descent) compared to Caucasians [<xref ref-type="bibr" rid="CR9">9</xref>–<xref ref-type="bibr" rid="CR11">11</xref>]. Genetic polymorphisms [<xref ref-type="bibr" rid="CR12">12</xref>], higher prevalence of diabetes mellitus and hypertension, and other co-morbidities including hepatitis B virus (HBV), schistosomiasis and malaria infections ensure that renal dysfunction is common in West Africans regardless of HIV status. HIVAN is the most common HIV-related renal pathology in sub Saharan Africa [<xref ref-type="bibr" rid="CR13">13</xref>, <xref ref-type="bibr" rid="CR14">14</xref>]. It appears that the prevalence of HIV-related renal dysfunction, defined by estimated glomerular filtration rate (eGFR) <60 ml/min, may be higher among ART-naïve West Africans compared with those from East and Southern Africa [<xref ref-type="bibr" rid="CR7">7</xref>, <xref ref-type="bibr" rid="CR13">13</xref>, <xref ref-type="bibr" rid="CR15">15</xref>–<xref ref-type="bibr" rid="CR19">19</xref>].</p><p>The nucleotide reverse transcriptase inhibitor tenofovir disoproxil fumarate (TDF), which is active against HBV in addition to HIV, is now widely used in Africa. TDF is excreted through a combination of glomerular filtration and active tubular secretion, with uptake in the proximal tubule and secretion into the tubular space [<xref ref-type="bibr" rid="CR20">20</xref>]. Initial clinical trials described a favourable renal safety profile [<xref ref-type="bibr" rid="CR21">21</xref>, <xref ref-type="bibr" rid="CR22">22</xref>], however there were rare post-marketing reports of Fanconi’s syndrome (proximal tubulopathy) leading to glucosuria, phosphaturia, aminoaciduria and bicarbonate wasting [<xref ref-type="bibr" rid="CR23">23</xref>, <xref ref-type="bibr" rid="CR24">24</xref>]. Subsequent studies have found that TDF use causes a small but significant decrease in creatinine clearance (a surrogate for glomerular filtration) in both HIV positive and negative populations [<xref ref-type="bibr" rid="CR25">25</xref>, <xref ref-type="bibr" rid="CR26">26</xref>]. There has been increasing interest in TDF-associated tubular dysfunction (TD), the duration of TDF exposure appearing to play a part, with cumulative TDF exposure associated with increased risk of proximal TD in adults [<xref ref-type="bibr" rid="CR27">27</xref>–<xref ref-type="bibr" rid="CR30">30</xref>]. Genetic polymorphisms may cause a predisposition for TDF associated TD [<xref ref-type="bibr" rid="CR20">20</xref>]. Little is known about the prevalence of TD in Africa as it is difficult to screen for this complication in resource-poor areas, and few African studies have investigated markers of TD. We therefore undertook this study to determine the prevalence of renal dysfunction including TD in HIV-infected individuals taking ART in Ghana and examine potential associated risk factors including TDF exposure.</p></sec><sec id="Sec2" sec-type="materials|methods"><title>Methods</title><p>This was an observational cross-sectional single-centre study involving HIV-infected patients taking ART. This study was conducted at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. The Committee on Human Research Publications and Ethics at KATH approved the study. Patients were initiated on either zidovudine or stavudine with lamivudine, plus either nevirapine or efavirenz prior to 2010 when TDF became available. After this a small proportion of patients, included those identified with hepatitis B co-infection, were initiated on (or switched to) TDF. All patients ≥18 years old attending the HIV clinic who had been taking ART for at least 6 months and who gave informed consent during the study period were screened for renal dysfunction by urine dipsticks and serum creatinine. Demographic, medical and laboratory data was collected from case notes. Individuals with known causes of renal impairment or urinary tract infections (positive dipstick for leukocytes and nitrites), were excluded. Patients with ‘one plus’ or more of protein or glucose on dipsticks were considered positive for proteinuria or glycosuria, the latter only if a blood glucose was <9 mmol/L. To further define the level and characteristics of proteinuria in a (randomly-selected) subset of individuals with proteinuria, spot urine protein:creatinine (uPCR), urine albumin:creatinine (uACR) and urinary albumin:protein (uAPR) ratios were calculated. Creatinine clearance (CrCl) was calculated using the Cockroft-Gault equation, based on local practice patterns.</p><p>In a subset of patients – all those who had sufficient volumes of urine and blood specimens - fractional phosphate and urate excretion was measured, in addition to glycosuria and uAPR, to identify TD. TD was defined as having two or more of the following: fractional phosphate excretion >18 %, fractional urate excretion >15 %, normo-glycaemic glycosuria, proteinuria (uPCR > 20 mg/mmol) with uAPR < 0.4. Descriptive results of continuous variables were expressed as medians and interquartile ranges. Continuous variables were compared using Student’s <italic>t</italic> test or Wilcoxon rank sum test, as required. For the comparison of proportions, the Chi-squared test was used, with Fisher’s corrections applied when needed. Univariate and multivariate logistic regression analyses were performed to identify factors associated with proteinuria or TD. Parameters with <italic>p</italic> < 0.1 in the univariate analysis were entered into a stepwise multivariate analysis. All statistics were conducted using SAS, version 9.3.</p></sec><sec id="Sec3" sec-type="results"><title>Results</title><p>In total, 367 patients were screened for evidence of renal dysfunction with urine dipsticks and blood creatinine measurement, and 37 excluded due to evidence of urinary tract infection or other causes of renal impairment, including diabetes and hypertension. Of the 330 remaining, who had been taking ART for a median of 24 (IQR 15–48) months, 101 were taking TDF for a median of 20 (12–14) months, with the remainder taking either stavudine or zidovudine with lamivudine. The characteristics of this population are shown in Table <xref rid="Tab1" ref-type="table">1</xref>. Demographic characteristics were similar amongst patient taking or not taking TDF. Proteinuria was common, found in 37 % of the entire cohort, and confirmed in 20/167 (12 %) patients with uPCRs >20 mg/mmol. 7 % of patients had CrCl <60 ml/min/1.73m<sup>2</sup>. TD was found in 12 of 82 (15 %) patients who were evaluated. Patients on TDF were more likely to be HBV co-infected (HBsAg+), have glycosuria and proteinuria on dipsticks, had significantly higher uPCRs (10.8 vs 5.7 mg/mmol, <italic>p</italic> < 0.001) and lower uAPRs (0.24 vs 0.58, <italic>p</italic> < 0.001), with 35 % of those on TDF (<italic>vs.</italic> 6 % not on TDF) satisfying the criteria for TD.<table-wrap id="Tab1"><label>Table 1</label><caption><p>Characteristics of the study population</p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="2"></th><th>Taking TDF</th><th>Not taking TDF</th><th>All patients</th><th rowspan="2"><italic>p</italic></th></tr><tr><th>(<italic>n</italic> = 101)</th><th>(<italic>n</italic> = 229)</th><th>(<italic>n</italic> = 330)</th></tr></thead><tbody><tr><td>Female, No. (%)</td><td>82 (81)</td><td>165 (72)</td><td>247 (75)</td><td>0.08</td></tr><tr><td>Age, Median (IQR), years</td><td>38 (34–46)</td><td>40 (36–46)</td><td>39 (35–46)</td><td>0.09</td></tr><tr><td>BMI, Median (IQR), kg/m<sup>2</sup></td><td>22.8 (21.5–25.3)</td><td>22.9 (20.3–27.1)</td><td>22.9 (20.5-26.6)</td><td>0.11</td></tr><tr><td>Nadir CD4 Median (IQR), cells/μl</td><td>164 (94–265)</td><td>186 (76–297)</td><td>185 (79–297)</td><td>0.79</td></tr><tr><td>Current CD4 Median (IQR), cells/μl</td><td>545 (337–679)</td><td>456 (335–630)</td><td>463 (329–640)</td><td>0.22</td></tr><tr><td>CrCl<sup>d</sup>, Median (IQR), ml/min/1.73m<sup>2</sup></td><td>99 (78–118)</td><td>96 (77–126)</td><td>95 (77–118)</td><td>0.21</td></tr><tr><td>CrCl < 60 ml/min/1.73 m<sup>2</sup>, No (%)</td><td>5 (5)</td><td>19 (8)</td><td>24 (7)</td><td>0.28</td></tr><tr><td>Efavirenz-based ART, No. (%)<sup>b</sup></td><td>71 (70)</td><td>147 (64)</td><td>218 (66)</td><td>0.28</td></tr><tr><td>Duration on tenofovir, Median (IQR), months</td><td>20 (12–24)</td><td></td><td></td><td></td></tr><tr><td>HBsAg positive<sup>a</sup>, No. (%)</td><td>20/56 (36)</td><td>8/101 (8)</td><td>28/157 (18)</td><td>0.0004</td></tr><tr><td>Proteinuria (dipstick), No. (%)</td><td>62 (61)</td><td>73 (32)</td><td>123 (37)</td><td><0.0001</td></tr><tr><td>uPCR<sup>b</sup>, Median (IQR), mg/mmol</td><td>10.8 (6.8–15.1)</td><td>5.7 (3.3–10.4)</td><td>7.7 (5.2–12.9)</td><td><0.0001</td></tr><tr><td>uACR<sup>b</sup>, Median (IQR), mg/mmol</td><td>2 (0.58–2.4)</td><td>2.1 (1.0–4.6)</td><td>2 (0.7–3.4)</td><td>0</td></tr><tr><td>uAPR<sup>e</sup>, Median (IQR), mg</td><td>0.24 (0.1–0.4)</td><td>0.58 (0.4–0.6)</td><td>0.43 (0.2–0.6)</td><td>0.0006</td></tr><tr><td>Fractional phosphate excretion > 18 %<sup>d</sup>, No. (%)</td><td>2/28 (7)</td><td>6/54 (11)</td><td>8/82 (10)</td><td>0.57</td></tr><tr><td>Fractional urate excretion > 15 %<sup>d</sup>, No. (%)</td><td>1/28 (4)</td><td>4/54 (7)</td><td>5/82 (6)</td><td>0.49</td></tr><tr><td>Glycosuria (dipstick), No. (%)</td><td>24 (24)</td><td>5 (2)</td><td>29 (9)</td><td><0.0001</td></tr></tbody></table><table-wrap-foot><p><italic>TDF</italic> tenofovir disoproxil fumarate, <italic>BMI</italic> body mass index, <italic>CrCl</italic> estimated creatinine clearance (by Cockcroft Gault formula), <italic>uPCR</italic> urinary protein:creatinine ratio, <italic>uACR</italic> urinary albumin:creatinine ratio, <italic>uAPR</italic> urinary albumin:protein ratio. <sup>a</sup><italic>HBsAg</italic> hepatitis B surface antigen (based on a subset of 157 patients)</p><p><sup>b</sup>Based on subset of 161 patients. <sup>c</sup>Most other patient were taking nevirapine. <sup>d</sup> Based on subset of 82 patients</p><p><sup>e</sup>Where uPCR > 20 mg/mmol</p></table-wrap-foot></table-wrap></p><p>Univariate and multivariate analyses of factors associated with dipstick proteinuria (in the entire population) and TD (in a subset of 82 patients) are shown in Table <xref rid="Tab2" ref-type="table">2</xref>. Younger age and lower baseline CD4 count were marginally associated with proteinuria, odds ratio (OR) 0.77 (95 % CI, 0.59–1.00) and 0.88 (0.77–1.01) respectively, as was TDF use, OR 1.82 (1.12–2.95). Factors independently associated with proteinuria were lower baseline CD4 count, adjusted odds ratio (aOR) 0.86 per 100 cell increment (0.74–0.99), and TDF use, aOR 2.74 (1.38–5.43). In a sensitivity analysis, use of TDF was significantly associated with proteinuria, unadjusted OR of 3.56 (1.21-10.50), <italic>p</italic> = 0.02, where only patients with confirmed uPCR > 20 (not dipstick-only proteinuria) were included. Similar results were also found where only patients with dipstick proteinuria >1+ were included. Although lower age was associated with TD in univariate analysis, the only factor associated with TD in both univariate and multivariate analyses was TDF use, aOR 3.43 (1.10–10.69). Of note, duration of TDF therapy was not significantly associated with odds of proteinuria, uPCR, or TD.<table-wrap id="Tab2"><label>Table 2</label><caption><p>Predictors of proteinuria and tubular dysfunction in HIV-infected Ghanaians</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Variable</th><th colspan="4">Proteinuria</th><th colspan="4">Tubular dysfunction</th></tr><tr><th></th><th>OR (95 % CI)</th><th><italic>p</italic></th><th>aOR (95 % CI)</th><th><italic>p</italic></th><th>OR (95 % CI)</th><th><italic>p</italic></th><th>aOR (95 % CI)</th><th><italic>p</italic></th></tr></thead><tbody><tr><td>Age/10 years</td><td>0.77 (0.59–1.00)</td><td>0.05</td><td>0.74 (0.54–1.01)</td><td>0.06</td><td>0.58 (0.35–0.98)</td><td>0.04</td><td>0.62 (0.36–1.06)</td><td>0.08</td></tr><tr><td>Baseline CD4/100 cells/mm<sup>3</sup></td><td>0.88 (0.77–1.01)</td><td>0.07</td><td>0.86 (0.74–0.99)</td><td>0.04</td><td>1.11 (0.88–1.40)</td><td>0.38</td><td></td><td></td></tr><tr><td>Gender</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Female</td><td>1.05 (0.63–1.78)</td><td>0.84</td><td></td><td></td><td>0.96 (0.35–2.61)</td><td>0.93</td><td></td><td></td></tr><tr><td>Male</td><td>1</td><td></td><td></td><td></td><td>1</td><td></td><td></td><td></td></tr><tr><td>BMI /5 kg/m<sup>2</sup></td><td>0.88 (0.69–1.12)</td><td>0.29</td><td></td><td></td><td>0.83 (0.50–1.38)</td><td>0.47</td><td></td><td></td></tr><tr><td>Each year on ART</td><td>0.95 (0.84–1.07)</td><td>0.38</td><td></td><td></td><td>0.92 (0.69–1.21)</td><td>0.53</td><td></td><td></td></tr><tr><td>Use of TDF</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Yes</td><td>1.82 (1.12–2.95)</td><td>0.01</td><td>2.74 (1.38–5.43)</td><td>0.004</td><td>3.83 (1.24–11.77)</td><td>0.02</td><td>3.43 (1.10–10.69)</td><td>0.03</td></tr><tr><td>No</td><td>1</td><td></td><td>1</td><td></td><td>1</td><td></td><td>1</td><td></td></tr><tr><td>Current CD4/100 cells/mm<sup>3</sup></td><td>0.98 (0.89–1.08)</td><td>0.65</td><td></td><td></td><td>1.09 (0.93–1.29)</td><td>0.29</td><td></td><td></td></tr><tr><td>Duration on TDF/1yr</td><td>1.00 (0.97–1.03)</td><td>0.86</td><td></td><td></td><td>1.13 (0.73–1.76)</td><td>0.57</td><td></td><td></td></tr><tr><td>HBV Serology</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HBsAg +</td><td>0.81 (0.36–1.85)</td><td>0.62</td><td></td><td></td><td>1.93 (0.49–7.56)</td><td>0.34</td><td></td><td></td></tr><tr><td>HBsAg -</td><td>1</td><td></td><td></td><td></td><td>1</td><td></td><td></td><td></td></tr></tbody></table><table-wrap-foot><p><italic>OR</italic> odds ratio, <italic>aOR</italic> adjusted odds ratio, <italic>TDF</italic> tenofovir disoproxil fumarate, <italic>BMI</italic> body mass index, <italic>ART</italic> antiretroviral therapy, <italic>HBV</italic> hepatitis B virus</p></table-wrap-foot></table-wrap></p></sec><sec id="Sec4" sec-type="discussion"><title>Discussion</title><p>Previous studies of populations taking TDF, including some in Africa, have shown that significant declines in renal function are rare [<xref ref-type="bibr" rid="CR7">7</xref>, <xref ref-type="bibr" rid="CR31">31</xref>, <xref ref-type="bibr" rid="CR32">32</xref>]. However only the DART study, based in East and Southern Africa, has followed patients beyond 2 years [<xref ref-type="bibr" rid="CR29">29</xref>], and to our knowledge no studies have assessed TD in addition to declines in estimated glomerular filtration rates (eGFR)/CrCl or proteinuria in Africa. We postulated that proteinuria may be more frequent in West Africans taking ART due to a genetic predisposition and other factors such as HBV co-infection, which is common in Ghana [<xref ref-type="bibr" rid="CR33">33</xref>] and has been associated with renal dysfunction in HIV-infected patients [<xref ref-type="bibr" rid="CR34">34</xref>]. We also postulated that the phasing out of stavudine and zidovudine in the Ghana ART programme, and their gradual replacement with TDF from 2010, might lead to an increase in TD in patients on TDF-based ART. Our study has shown strong evidence of both TD and proteinuria being associated with TDF use. It has also demonstrated that whilst CrCl < 60mls/min is relatively rare in this population, TD is common (found in 15 % of all patients and 35 % of those on TDF) as is proteinuria, which was found in over one third of the population studied. Cross-sectional studies in European populations have identified between 7–22 % of patients on ART having evidence of TD [<xref ref-type="bibr" rid="CR20">20</xref>, <xref ref-type="bibr" rid="CR28">28</xref>–<xref ref-type="bibr" rid="CR30">30</xref>], using different definitions of TD, which is similar to the overall rate found in Ghana however lower than that found in patients taking TDF. Given that use of protease inhibitors has also been associated with TD, since no patients receiving protease inhibitors had features of TD, it is likely most ART-related TD was due to TDF alone [<xref ref-type="bibr" rid="CR29">29</xref>, <xref ref-type="bibr" rid="CR35">35</xref>]. As in other studies, very few of the patients meeting our definition of TD had evidence of clinically-significant TD or Fanconi syndrome, and the long-term significance of this finding is uncertain.</p><p>Hardly any studies outside Africa have identified such a high proportion of ART-treated patients having proteinuria as ours. High rates of proteinuria have been noted in two other studies in Africa, however neither study distinguished the type of proteinuria in terms of albumin and total protein [<xref ref-type="bibr" rid="CR12">12</xref>, <xref ref-type="bibr" rid="CR36">36</xref>]. This study demonstrated that in patients with significant proteinuria, those taking TDF had a lower albumin:protein ratios which is characteristic of tubular rather than glomerular dysfunction [<xref ref-type="bibr" rid="CR37">37</xref>], indicating that HIVAN was probably not the predominant pathology causing renal dysfunction. Interestingly, lower age was associated with proteinuria in our study, in contrast to older age being more often associated with proteinuria, although this might be explained by orthostatic proteinuria which is common in young adults. Given increasing evidence that an alternative form of tenofovir, tenofovir alafenamide (TAF), is less nephrotoxic than TDF [<xref ref-type="bibr" rid="CR38">38</xref>], and is likely to replace TDF over the next decade, it is perhaps less likely that significant numbers of patients will develop TDF-associated renal dysfunction or chronic kidney disease (CKD).</p><p>Limitations of this study include the relatively small sample of patients who were tested for features of TD and numbers who had available HBV serology, limiting the power of the analyses to demonstrate correlations of postulated risk factors with TD. Given the strong association between TDF use and HBsAg + status, this may also have introduced confounding by indication. Furthermore, the prevalence of proteinuria and TD may have been over-estimated given that this was a cross-sectional study without repeated measurement, and in just over half of patients proteinuria was not confirmed or quantified by measuring uPCR.</p></sec><sec id="Sec5" sec-type="conclusion"><title>Conclusions</title><p>In summary this study has shown that both TD and proteinuria are common amongst Ghanaians taking ART, and TDF use is independently associated with both of these outcomes. Further studies are needed assessing clinical outcomes including decline in eGRF/CrCl and mortality in this population to evaluate the clinical significance of these findings.</p></sec></body><back><glossary><title>Abbreviations</title><def-list><def-item><term>HIV</term><def><p>Human immunodeficiency virus</p></def></def-item><def-item><term>HIVAN</term><def><p>HIV-associated nephropathy</p></def></def-item><def-item><term>ART</term><def><p>Antiretroviral therapy</p></def></def-item><def-item><term>ESRD</term><def><p>End stage renal disease</p></def></def-item><def-item><term>HBV</term><def><p>Hepatitis B virus</p></def></def-item><def-item><term>TD</term><def><p>Tubular dysfunction</p></def></def-item></def-list></glossary><fn-group><fn><p><bold>Competing interests</bold></p><p>DRC has received reimbursements from Gilead and ViiV for attending conferences. None of the remaining authors have any relevant interests to declare.</p></fn><fn><p><bold>Authors’ contributions</bold></p><p>DRC designed the study and assisted with analysis and manuscript preparation. FSS, assisted with study design, analysed the data and critically evaluated the manuscript. EK, VP, DO and ALO assisted with sample analysis, data collection and critically evaluated the manuscript. RP and GBA assisted with study design and critically evaluated the manuscript. All authors read and approved the final manuscript.</p></fn></fn-group><ack><title>Acknowledgements</title><p>We are grateful to the nurses and patients at KATH HIV clinic for assistance with this study. We would also like to acknowledge Daniel Chadwick, Edwin Eshun, Edward Allen and Rosie Keegan’s assistance with data and sample collection. This study received financial support from the South Tees Infectious Diseases Research Fund.</p></ack><ref-list id="Bib1"><title>References</title><ref id="CR1"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Szczech</surname><given-names>LA</given-names></name><name><surname>Gange</surname><given-names>SJ</given-names></name><name><surname>van der Horst</surname><given-names>C</given-names></name><name><surname>Bartlett</surname><given-names>JA</given-names></name><name><surname>Young</surname><given-names>M</given-names></name><name><surname>Cohen</surname><given-names>MH</given-names></name><etal></etal></person-group><article-title>Predictors of proteinuria and renal failure among women with HIV infection</article-title><source>Kidney Int.</source><year>2002</year><volume>61</volume><fpage>195</fpage><lpage>202</lpage><pub-id pub-id-type="doi">10.1046/j.1523-1755.2002.00094.x</pub-id><pub-id pub-id-type="pmid">11786101</pub-id></element-citation></ref><ref id="CR2"><label>2.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mocroft</surname><given-names>A</given-names></name><name><surname>Kirk</surname><given-names>O</given-names></name><name><surname>Reiss</surname><given-names>P</given-names></name><name><surname>De Wit</surname><given-names>S</given-names></name><name><surname>Sedlacek</surname><given-names>D</given-names></name><name><surname>Beniowski</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients</article-title><source>AIDS.</source><year>2010</year><volume>24</volume><fpage>1667</fpage><lpage>78</lpage><pub-id pub-id-type="doi">10.1097/QAD.0b013e328339fe53</pub-id><pub-id pub-id-type="pmid">20523203</pub-id></element-citation></ref><ref id="CR3"><label>3.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Daar</surname><given-names>ES</given-names></name><name><surname>Tierney</surname><given-names>C</given-names></name><name><surname>Fischl</surname><given-names>MA</given-names></name><name><surname>Sax</surname><given-names>PE</given-names></name><name><surname>Mollan</surname><given-names>K</given-names></name><name><surname>Budhathoki</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1</article-title><source>Ann Intern Med.</source><year>2011</year><volume>154</volume><fpage>445</fpage><lpage>56</lpage><pub-id pub-id-type="doi">10.7326/0003-4819-154-7-201104050-00316</pub-id><pub-id pub-id-type="pmid">21320923</pub-id></element-citation></ref><ref id="CR4"><label>4.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Campbell</surname><given-names>LJ</given-names></name><name><surname>Ibrahim</surname><given-names>F</given-names></name><name><surname>Fisher</surname><given-names>M</given-names></name><name><surname>Holt</surname><given-names>SG</given-names></name><name><surname>Hendry</surname><given-names>BM</given-names></name><name><surname>Post</surname><given-names>FA</given-names></name></person-group><article-title>Spectrum of chronic kidney disease in HIV-infected patients</article-title><source>HIV Med.</source><year>2009</year><volume>10</volume><fpage>329</fpage><lpage>36</lpage><pub-id pub-id-type="doi">10.1111/j.1468-1293.2008.00691.x</pub-id><pub-id pub-id-type="pmid">19226409</pub-id></element-citation></ref><ref id="CR5"><label>5.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lucas</surname><given-names>GM</given-names></name><name><surname>Eustace</surname><given-names>JA</given-names></name><name><surname>Sozio</surname><given-names>S</given-names></name><name><surname>Mentari</surname><given-names>EK</given-names></name><name><surname>Appiah</surname><given-names>KA</given-names></name><name><surname>Moore</surname><given-names>RD</given-names></name></person-group><article-title>Highly active antiretroviral therapy and the incidence of HIV-1-associated nephropathy: a 12-year cohort study</article-title><source>AIDS.</source><year>2004</year><volume>18</volume><fpage>541</fpage><lpage>6</lpage><pub-id pub-id-type="doi">10.1097/00002030-200402200-00022</pub-id><pub-id pub-id-type="pmid">15090808</pub-id></element-citation></ref><ref id="CR6"><label>6.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Atta</surname><given-names>MG</given-names></name></person-group><article-title>Diagnosis and natural history of HIV-associated nephropathy</article-title><source>Adv Chronic Kidney Dis</source><year>2010</year><volume>17</volume><fpage>52</fpage><lpage>8</lpage><pub-id pub-id-type="doi">10.1053/j.ackd.2009.08.005</pub-id><pub-id pub-id-type="pmid">20005489</pub-id></element-citation></ref><ref id="CR7"><label>7.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reid</surname><given-names>A</given-names></name><name><surname>Stöhr</surname><given-names>W</given-names></name><name><surname>Walker</surname><given-names>AS</given-names></name><name><surname>Williams</surname><given-names>IG</given-names></name><name><surname>Kityo</surname><given-names>C</given-names></name><name><surname>Hughes</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Severe renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapy</article-title><source>Clin Infect Dis.</source><year>2008</year><volume>46</volume><fpage>1271</fpage><lpage>81</lpage><pub-id pub-id-type="doi">10.1086/533468</pub-id><pub-id pub-id-type="pmid">18444867</pub-id></element-citation></ref><ref id="CR8"><label>8.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gupta</surname><given-names>SK</given-names></name><name><surname>Parker</surname><given-names>RA</given-names></name><name><surname>Robbins</surname><given-names>GK</given-names></name><name><surname>Dubé</surname><given-names>MP</given-names></name></person-group><article-title>The effects of highly active antiretroviral therapy on albuminuria in HIV-infected persons: results from a randomized trial</article-title><source>Nephrol Dial Transplant.</source><year>2005</year><volume>20</volume><fpage>2237</fpage><lpage>42</lpage><pub-id pub-id-type="doi">10.1093/ndt/gfi053</pub-id><pub-id pub-id-type="pmid">16105869</pub-id></element-citation></ref><ref id="CR9"><label>9.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kopp</surname><given-names>JB</given-names></name><name><surname>Winkler</surname><given-names>C</given-names></name></person-group><article-title>HIV-associated nephropathy in African Americans</article-title><source>Kidney international</source><year>2003</year><volume>83</volume><fpage>43</fpage><lpage>9</lpage><pub-id pub-id-type="doi">10.1046/j.1523-1755.63.s83.10.x</pub-id></element-citation></ref><ref id="CR10"><label>10.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rostand</surname><given-names>SG</given-names></name><name><surname>Kirk</surname><given-names>KA</given-names></name><name><surname>Rutsky</surname><given-names>EA</given-names></name><name><surname>Pate</surname><given-names>BA</given-names></name></person-group><article-title>Racial differences in the incidence of treatment for end-stage renal disease</article-title><source>N Engl J Med.</source><year>1982</year><volume>306</volume><fpage>1276</fpage><lpage>9</lpage><pub-id pub-id-type="doi">10.1056/NEJM198205273062106</pub-id><pub-id pub-id-type="pmid">7040967</pub-id></element-citation></ref><ref id="CR11"><label>11.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Klag</surname><given-names>MJ</given-names></name><name><surname>Whelton</surname><given-names>PK</given-names></name><name><surname>Randall</surname><given-names>BL</given-names></name><name><surname>Neaton</surname><given-names>JD</given-names></name><name><surname>Brancati</surname><given-names>FL</given-names></name><name><surname>Stamler</surname><given-names>J</given-names></name></person-group><article-title>End-stage renal disease in African-American and white men. 16-year MRFIT findings</article-title><source>JAMA</source><year>1997</year><volume>277</volume><fpage>1293</fpage><lpage>8</lpage><pub-id pub-id-type="doi">10.1001/jama.1997.03540400043029</pub-id><pub-id pub-id-type="pmid">9109467</pub-id></element-citation></ref><ref id="CR12"><label>12.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Padullés</surname><given-names>A</given-names></name><name><surname>Rama</surname><given-names>I</given-names></name><name><surname>Llaudo</surname><given-names>I</given-names></name><name><surname>Lloberas</surname><given-names>N</given-names></name></person-group><article-title>Developments in renal pharmacogenomics and applications in chronic kidney disease</article-title><source>Pharmgenomics Pers Med.</source><year>2014</year><volume>7</volume><fpage>251</fpage><lpage>66</lpage><pub-id pub-id-type="pmid">25206311</pub-id></element-citation></ref><ref id="CR13"><label>13.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Okafor</surname><given-names>UH</given-names></name><name><surname>Unuigbe</surname><given-names>EI</given-names></name><name><surname>Ojogwu</surname><given-names>LI</given-names></name><name><surname>Oviasu</surname><given-names>E</given-names></name><name><surname>Wokoma</surname><given-names>FS</given-names></name></person-group><article-title>Renal disease in HIV infected patients at University of Benin Teaching Hospital in Nigeria</article-title><source>Afr Health Sci.</source><year>2011</year><volume>11</volume><issue>Suppl 1</issue><fpage>S28</fpage><lpage>33</lpage><pub-id pub-id-type="pmid">22135641</pub-id></element-citation></ref><ref id="CR14"><label>14.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fabian</surname><given-names>J</given-names></name><name><surname>Naicker</surname><given-names>S</given-names></name></person-group><article-title>HIV and kidney disease in sub-Saharan Africa</article-title><source>Nat Rev Nephrol</source><year>2009</year><volume>5</volume><fpage>591</fpage><lpage>8</lpage><pub-id pub-id-type="doi">10.1038/nrneph.2009.141</pub-id><pub-id pub-id-type="pmid">19776781</pub-id></element-citation></ref><ref id="CR15"><label>15.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wools-Kaloustian</surname><given-names>K</given-names></name><name><surname>Gupta</surname><given-names>SK</given-names></name><name><surname>Muloma</surname><given-names>E</given-names></name><name><surname>Owino-Ong'or</surname><given-names>W</given-names></name><name><surname>Sidle</surname><given-names>J</given-names></name><name><surname>Aubrey</surname><given-names>RW</given-names></name></person-group><article-title>Renal disease in an antiretroviral-naïve HIV infected outpatient population in Western Kenya</article-title><source>Nephrol Dial Transplant.</source><year>2007</year><volume>22</volume><fpage>2208</fpage><lpage>12</lpage><pub-id pub-id-type="doi">10.1093/ndt/gfm223</pub-id><pub-id pub-id-type="pmid">17652119</pub-id></element-citation></ref><ref id="CR16"><label>16.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sarfo</surname><given-names>FS</given-names></name><name><surname>Keegan</surname><given-names>R</given-names></name><name><surname>Appiah</surname><given-names>L</given-names></name><name><surname>Shakoor</surname><given-names>S</given-names></name><name><surname>Phillips</surname><given-names>R</given-names></name><name><surname>Norman</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>High prevalence of renal dysfunction and association with risk of death amongst HIV-infected Ghanaians</article-title><source>J Infect.</source><year>2013</year><volume>67</volume><fpage>43</fpage><lpage>50</lpage><pub-id pub-id-type="doi">10.1016/j.jinf.2013.03.008</pub-id><pub-id pub-id-type="pmid">23542785</pub-id></element-citation></ref><ref id="CR17"><label>17.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Han</surname><given-names>TM</given-names></name><name><surname>Naicker</surname><given-names>S</given-names></name><name><surname>Ramdial</surname><given-names>PK</given-names></name><name><surname>Assounga</surname><given-names>AG</given-names></name></person-group><article-title>A cross-sectional study of HIV-seropositive patients with varying degrees of proteinuria in South Africa</article-title><source>Kidney Int.</source><year>2006</year><volume>69</volume><fpage>2243</fpage><lpage>50</lpage><pub-id pub-id-type="doi">10.1038/sj.ki.5000339</pub-id><pub-id pub-id-type="pmid">16672914</pub-id></element-citation></ref><ref id="CR18"><label>18.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mulenga</surname><given-names>LB</given-names></name><name><surname>Kruse</surname><given-names>G</given-names></name><name><surname>Lakhi</surname><given-names>S</given-names></name><name><surname>Cantrell</surname><given-names>RA</given-names></name><name><surname>Reid</surname><given-names>SE</given-names></name><name><surname>Zulu</surname><given-names>I</given-names></name><etal></etal></person-group><article-title>Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka</article-title><source>Zambia AIDS</source><year>2008</year><volume>22</volume><issue>14</issue><fpage>1821</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">18753939</pub-id></element-citation></ref><ref id="CR19"><label>19.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jao</surname><given-names>J</given-names></name><name><surname>Lo</surname><given-names>W</given-names></name><name><surname>Toro</surname><given-names>PL</given-names></name><name><surname>Wyatt</surname><given-names>C</given-names></name><name><surname>Palmer</surname><given-names>D</given-names></name><name><surname>Abrams</surname><given-names>EJ</given-names></name><etal></etal></person-group><article-title>Factors associated with decreased kidney function in HIV-infected adults enrolled in the MTCT-Plus Initiative in sub-Saharan Africa</article-title><source>J Acquir Immune Defic Syndr</source><year>2011</year><volume>57</volume><issue>1</issue><fpage>40</fpage><lpage>5</lpage><pub-id pub-id-type="doi">10.1097/QAI.0b013e31821008eb</pub-id><pub-id pub-id-type="pmid">21266908</pub-id></element-citation></ref><ref id="CR20"><label>20.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rodriguez-Nóvoa</surname><given-names>S</given-names></name><name><surname>Labarga</surname><given-names>P</given-names></name><name><surname>Soriano</surname><given-names>V</given-names></name><name><surname>Egan</surname><given-names>D</given-names></name><name><surname>Albalater</surname><given-names>M</given-names></name><name><surname>Morello</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Predictors of kidney tubular dysfunction in HIV-infected patients treated with Tenofovir: a pharmacogenetic study</article-title><source>Clin Infect Dis.</source><year>2009</year><volume>48</volume><fpage>108</fpage><lpage>16</lpage><pub-id pub-id-type="doi">10.1086/598507</pub-id><pub-id pub-id-type="pmid">19049436</pub-id></element-citation></ref><ref id="CR21"><label>21.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Squires</surname><given-names>K</given-names></name><name><surname>Pozniak</surname><given-names>AL</given-names></name><name><surname>Pierone</surname><given-names>G</given-names><suffix>Jr</suffix></name><name><surname>Steinhart</surname><given-names>CR</given-names></name><name><surname>Berger</surname><given-names>D</given-names></name><name><surname>Bellos</surname><given-names>NC</given-names></name><etal></etal></person-group><article-title>Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial</article-title><source>Ann Intern Med.</source><year>2003</year><volume>139</volume><fpage>313</fpage><lpage>20</lpage><pub-id pub-id-type="doi">10.7326/0003-4819-139-5_Part_1-200309020-00006</pub-id><pub-id pub-id-type="pmid">12965939</pub-id></element-citation></ref><ref id="CR22"><label>22.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gallant</surname><given-names>JE</given-names></name><name><surname>Staszewski</surname><given-names>S</given-names></name><name><surname>Pozniak</surname><given-names>AL</given-names></name><name><surname>DeJesus</surname><given-names>E</given-names></name><name><surname>Suleiman</surname><given-names>JM</given-names></name><name><surname>Miller</surname><given-names>MD</given-names></name><etal></etal></person-group><article-title>Efficacy and safety of Tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial</article-title><source>JAMA.</source><year>2004</year><volume>292</volume><fpage>191</fpage><lpage>201</lpage><pub-id pub-id-type="doi">10.1001/jama.292.2.191</pub-id><pub-id pub-id-type="pmid">15249568</pub-id></element-citation></ref><ref id="CR23"><label>23.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Quimby</surname><given-names>D</given-names></name><name><surname>Brito</surname><given-names>MO</given-names></name></person-group><article-title>Fanconi syndrome associated with use of tenofovir in HIV-infected patients: a case report and review of the literature</article-title><source>AIDS Read.</source><year>2005</year><volume>15</volume><fpage>357</fpage><lpage>64</lpage><pub-id pub-id-type="pmid">16044577</pub-id></element-citation></ref><ref id="CR24"><label>24.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Malik</surname><given-names>A</given-names></name><name><surname>Abraham</surname><given-names>P</given-names></name><name><surname>Malik</surname><given-names>N</given-names></name></person-group><article-title>Acute renal failure and Fanconi syndrome in an AIDS patient on Tenofovir treatment--case report and review of literature</article-title><source>J Infect.</source><year>2005</year><volume>51</volume><fpage>61</fpage><lpage>5</lpage><pub-id pub-id-type="doi">10.1016/j.jinf.2004.08.031</pub-id></element-citation></ref><ref id="CR25"><label>25.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Young</surname><given-names>B</given-names></name><name><surname>Buchacz</surname><given-names>K</given-names></name><name><surname>Baker</surname><given-names>RK</given-names></name><name><surname>Moorman</surname><given-names>AC</given-names></name><name><surname>Wood</surname><given-names>KC</given-names></name><name><surname>Chmiel</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Renal function in Tenofovir -exposed and Tenofovir -unexposed patients receiving highly active antiretroviral therapy in the HIV Outpatient Study</article-title><source>J Int Assoc Physicians AIDS Care (Chic)</source><year>2007</year><volume>6</volume><fpage>178</fpage><lpage>87</lpage><pub-id pub-id-type="doi">10.1177/1545109707300676</pub-id><pub-id pub-id-type="pmid">17579126</pub-id></element-citation></ref><ref id="CR26"><label>26.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Solomon</surname><given-names>MM</given-names></name><name><surname>Lama</surname><given-names>JR</given-names></name><name><surname>Glidden</surname><given-names>DV</given-names></name><name><surname>Mulligan</surname><given-names>K</given-names></name><name><surname>McMahan</surname><given-names>V</given-names></name><name><surname>Liu</surname><given-names>AY</given-names></name><etal></etal></person-group><article-title>Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis</article-title><source>AIDS.</source><year>2014</year><volume>28</volume><fpage>851</fpage><lpage>9</lpage><pub-id pub-id-type="doi">10.1097/QAD.0000000000000156</pub-id><pub-id pub-id-type="pmid">24499951</pub-id></element-citation></ref><ref id="CR27"><label>27.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Purswani</surname><given-names>M</given-names></name><name><surname>Patel</surname><given-names>K</given-names></name><name><surname>Kopp</surname><given-names>JB</given-names></name><name><surname>Seage</surname><given-names>GR</given-names><suffix>3rd</suffix></name><name><surname>Chernoff</surname><given-names>MC</given-names></name><name><surname>Hazra</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection</article-title><source>Pediatr Infect Dis J.</source><year>2013</year><volume>32</volume><fpage>495</fpage><lpage>500</lpage><pub-id pub-id-type="doi">10.1097/INF.0b013e31827f4eff</pub-id><pub-id pub-id-type="pmid">23249917</pub-id></element-citation></ref><ref id="CR28"><label>28.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reynes</surname><given-names>J</given-names></name><name><surname>Cournil</surname><given-names>A</given-names></name><name><surname>Peyriere</surname><given-names>H</given-names></name><name><surname>Psomas</surname><given-names>C</given-names></name><name><surname>Guiller</surname><given-names>E</given-names></name><name><surname>Chatron</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Tubular and glomerular proteinuria in HIV- infected adults with estimated glomerular filtration rate ≥ 60ml/min per 1.73m<sup>2</sup></article-title><source>AIDS</source><year>2013</year><volume>27</volume><fpage>1295</fpage><lpage>302</lpage><pub-id pub-id-type="doi">10.1097/QAD.0b013e32835fac51</pub-id><pub-id pub-id-type="pmid">23925378</pub-id></element-citation></ref><ref id="CR29"><label>29.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dauchy</surname><given-names>FA</given-names></name><name><surname>Lawson-Ayayi</surname><given-names>S</given-names></name><name><surname>de La Faille</surname><given-names>R</given-names></name><name><surname>Bonnet</surname><given-names>F</given-names></name><name><surname>Rigothier</surname><given-names>C</given-names></name><name><surname>Mehsen</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy</article-title><source>Kidney Int.</source><year>2011</year><volume>80</volume><fpage>302</fpage><lpage>9</lpage><pub-id pub-id-type="doi">10.1038/ki.2011.124</pub-id><pub-id pub-id-type="pmid">21544066</pub-id></element-citation></ref><ref id="CR30"><label>30.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Labarga</surname><given-names>P</given-names></name><name><surname>Barreiro</surname><given-names>P</given-names></name><name><surname>Martin-Carbonero</surname><given-names>L</given-names></name><name><surname>Rodriguez-Novoa</surname><given-names>S</given-names></name><name><surname>Solera</surname><given-names>C</given-names></name><name><surname>Medrano</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with Tenofovir</article-title><source>AIDS.</source><year>2009</year><volume>23</volume><fpage>689</fpage><lpage>96</lpage><pub-id pub-id-type="doi">10.1097/QAD.0b013e3283262a64</pub-id><pub-id pub-id-type="pmid">19262355</pub-id></element-citation></ref><ref id="CR31"><label>31.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stöhr</surname><given-names>W</given-names></name><name><surname>Reid</surname><given-names>A</given-names></name><name><surname>Walker</surname><given-names>AS</given-names></name><name><surname>Ssali</surname><given-names>F</given-names></name><name><surname>Munderi</surname><given-names>P</given-names></name><name><surname>Mambule</surname><given-names>I</given-names></name><etal></etal></person-group><article-title>Glomerular dysfunction and associated risk factors over 4–5 years following antiretroviral therapy initiation in Africa</article-title><source>Antivir Ther.</source><year>2011</year><volume>16</volume><fpage>1011</fpage><lpage>20</lpage><pub-id pub-id-type="doi">10.3851/IMP1832</pub-id><pub-id pub-id-type="pmid">22024517</pub-id></element-citation></ref><ref id="CR32"><label>32.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mulenga</surname><given-names>L</given-names></name><name><surname>Musonda</surname><given-names>P</given-names></name><name><surname>Mwango</surname><given-names>A</given-names></name><name><surname>Vinikoor</surname><given-names>MJ</given-names></name><name><surname>Davies</surname><given-names>MA</given-names></name><name><surname>Mweemba</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Effect of Baseline Renal Function on Tenofovir -Containing Antiretroviral Therapy Outcomes in Zambia</article-title><source>Clin Infect Dis.</source><year>2014</year><volume>58</volume><fpage>1473</fpage><lpage>80</lpage><pub-id pub-id-type="doi">10.1093/cid/ciu117</pub-id><pub-id pub-id-type="pmid">24585558</pub-id></element-citation></ref><ref id="CR33"><label>33.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Geretti</surname><given-names>AM</given-names></name><name><surname>Patel</surname><given-names>M</given-names></name><name><surname>Sarfo</surname><given-names>FS</given-names></name><name><surname>Chadwick</surname><given-names>D</given-names></name><name><surname>Verheyen</surname><given-names>J</given-names></name><name><surname>Fraune</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Detection of highly prevalent hepatitis B virus coinfection among HIV-seropositive persons in Ghana</article-title><source>J Clin Microbiol.</source><year>2010</year><volume>48</volume><fpage>3223</fpage><lpage>30</lpage><pub-id pub-id-type="doi">10.1128/JCM.02231-09</pub-id><pub-id pub-id-type="pmid">20631103</pub-id></element-citation></ref><ref id="CR34"><label>34.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mocroft</surname><given-names>A</given-names></name><name><surname>Neuhaus</surname><given-names>J</given-names></name><name><surname>Peters</surname><given-names>L</given-names></name><name><surname>Ryom</surname><given-names>L</given-names></name><name><surname>Bickel</surname><given-names>M</given-names></name><name><surname>Grint</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>Hepatitis B and C co-infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults</article-title><source>PLoS One.</source><year>2012</year><volume>7</volume><pub-id pub-id-type="doi">10.1371/journal.pone.0040245</pub-id><pub-id pub-id-type="pmid">22911697</pub-id></element-citation></ref><ref id="CR35"><label>35.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Del Palacio</surname><given-names>M</given-names></name><name><surname>Romero</surname><given-names>S</given-names></name><name><surname>Casado</surname><given-names>JL</given-names></name></person-group><article-title>Proximal tubular renal dysfunction or damage in HIV-infected patients</article-title><source>AIDS Rev</source><year>2012</year><volume>14</volume><fpage>179</fpage><lpage>87</lpage><pub-id pub-id-type="pmid">22833061</pub-id></element-citation></ref><ref id="CR36"><label>36.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Msango</surname><given-names>L</given-names></name><name><surname>Downs</surname><given-names>JA</given-names></name><name><surname>Kalluvva</surname><given-names>SE</given-names></name><name><surname>Kidenya</surname><given-names>BR</given-names></name><name><surname>Kabangila</surname><given-names>R</given-names></name><name><surname>Johnson</surname><given-names>WD</given-names><suffix>Jr</suffix></name><etal></etal></person-group><article-title>Renal dysfunction among HIV-infected patients starting antiretroviral therapy</article-title><source>AIDS.</source><year>2011</year><volume>25</volume><fpage>1421</fpage><lpage>5</lpage><pub-id pub-id-type="doi">10.1097/QAD.0b013e328348a4b1</pub-id><pub-id pub-id-type="pmid">21572304</pub-id></element-citation></ref><ref id="CR37"><label>37.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sise</surname><given-names>ME</given-names></name><name><surname>Hirsch</surname><given-names>JS</given-names></name><name><surname>Canetta</surname><given-names>PA</given-names></name><name><surname>Herlitz</surname><given-names>L</given-names></name><name><surname>Mohan</surname><given-names>S</given-names></name></person-group><article-title>Nonalbumin proteinuria predominates in biopsy-proven Tenofovir nephrotoxicity</article-title><source>AIDS</source><year>2015</year><volume>29</volume><issue>8</issue><fpage>941</fpage><lpage>6</lpage><pub-id pub-id-type="doi">10.1097/QAD.0000000000000628</pub-id><pub-id pub-id-type="pmid">25784440</pub-id></element-citation></ref><ref id="CR38"><label>38.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mills</surname><given-names>A</given-names></name><name><surname>Crofoot</surname><given-names>G</given-names><suffix>Jr</suffix></name><name><surname>McDonald</surname><given-names>C</given-names></name><name><surname>Shalit</surname><given-names>P</given-names></name><name><surname>Flamm</surname><given-names>JA</given-names></name><name><surname>Gathe</surname><given-names>J</given-names><suffix>Jr</suffix></name><etal></etal></person-group><article-title>Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study</article-title><source>J Acquir Immune Defic Syndr</source><year>2015</year><volume>69</volume><issue>4</issue><fpage>439</fpage><lpage>45</lpage><pub-id pub-id-type="pmid">25867913</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:26627687" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a SidaGhanaV1
| This area was generated with Dilib version V0.6.31. |  |