TY - JOUR
T1 - Association of urinary biomarkers of kidney injury with estimated GFR decline in HIV-infected individuals following tenofovir disoproxil fumarate initiation
AU - Ascher, Simon B.
AU - Scherzer, Rebecca
AU - Estrella, Michelle M.
AU - Zhang, William R.
AU - Muiru, Anthony N.
AU - Jotwani, Vasantha
AU - Grunfeld, Carl
AU - Parikh, Chirag R.
AU - Gustafson, Deborah
AU - Young, Mary
AU - Sharma, Anjali
AU - Cohen, Mardge H.
AU - Ng, Derek K.
AU - Palella, Frank J.
AU - Witt, Mallory D.
AU - Ho, Ken
AU - Shlipak, Michael G.
N1 - Funding Information:
The MACSisfundedprimarilybytheNationalInstituteof Allergy and Infectious Diseases (NIAID), with additional cofunding from the National Cancer Institute (NCI) (U01-AI35039 to S.W., U01-AI35040 to R.D. and O.M.M., U01-AI35041 to C.R., U01-AI35042 to J.M., and U01-AI35043 to L.J. and G.D.), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute, and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by grant UL1-TR001079 (Johns Hopkins University Institute for Clinical and Translational Research) from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The WIHS is funded primarily by the NIAID (U01 AI103401 to M.C.K., U01 AI103408 to G.W. and I.O., U01 AI035004 to K.A., U01 AI031834 to H.M., U01 AI034993 to M.C., U01 AI034994 to S.G.K., U01 AI103397 toM.A.F.,U01AI103390toA.A.A.,U01AI034989toR.M.G.andP.C.T., U01 AI042590 to S.G, U01-HD-032632 to J.M.)., with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NCI, the NIDA, and theNIMH.Targetedsupplementalfundingforspecificprojectsisalso provided by the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women’s Health. WIHS datacollectionisalsosupportedbygrantsUL1-TR000004(University of California, San Francisco, Clinical and Translational Science Award), UL1-TR000454 (Atlanta Clinical and Translational Science Award), and P30-AI-050410 (Univeristy of North Carolina at Chapel Hill Center for AIDS Research). M.G.S. and R.S. are funded by grant R01AG034853-08 (National Institute of Aging).
Funding Information:
The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the National Cancer Institute (NCI) (U01-AI35039 to S.W., U01-AI35040 to R.D. and O.M.M., U01-AI35041 to C.R., U01-AI35042 to J.M., and U01-AI35043 to L.J. and G.D.), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute, and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by grant UL1-TR001079 (Johns Hopkins University Institute for Clinical and Translational Research) from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The WIHS is funded primarily by the NIAID (U01 AI103401 to M.C.K., U01 AI103408 to G.W. and I.O., U01 AI035004 to K.A., U01 AI031834 to H.M., U01 AI034993 to M.C., U01 AI034994 to S.G.K., U01 AI103397 to M.A.F., U01AI103390 to A.A.A., U01AI034989 to R.M.G. and P.C.T., U01 AI042590 to S.G, U01-HD-032632 to J.M.)., with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NCI, the NIDA, and the NIMH. Targeted supplemental fundingfor specific projects is also provided by the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women’s Health. WIHS data collectionis alsosupportedby grants UL1-TR000004 (University of California, San Francisco, Clinical and Translational Science Award), UL1-TR000454 (Atlanta Clinical and Translational Science Award), and P30-AI-050410 (Univeristy of North Carolina at Chapel Hill Center for AIDS Research). M.G.S. and R.S. are funded by grant R01AG034853-08 (National Institute of Aging).
Publisher Copyright:
© 2018 by the American Society of Nephrology.
PY - 2018/9/7
Y1 - 2018/9/7
N2 - Background and objectives Tenofovir disoproxil fumarate (tenofovir) is associated with elevated concentrations of biomarkers of kidney damage and dysfunction in individuals with HIV. The relationship of these kidney biomarkers with longitudinal kidney function decline is unknown. Design, setting, participants, & measurements We evaluated associations of 14 urinary biomarkers of kidney injury with changes in eGFR among 198 men and women with HIV who initiated tenofovir between 2009 and 2015 in the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study. Urinary biomarkers included albumin-to-creatinine ratio, α-1-microglobulin, β-2-microglobulin, cystatin C, kidney injury molecule-1 (KIM-1), IL-18, neutrophil gelatinase–associated lipocalin (NGAL), clusterin, osteopontin, uromodulin, monocyte chemoattractant protein-1, EGF, trefoil factor 3, and chitinase 3-like protein 1. We used multivariable linear mixed-effect models controlling for demographics, traditional kidney disease risk factors, and HIV-related risk factors to evaluate associations of baseline biomarkers with first-year changes in eGFR, and associations of year 1 and first-year change in biomarkers with changes in eGFR from year 1 to year 3. We used the least absolute shrinkage and selection operator method to identify a parsimonious set of biomarkers jointly associated with changes in eGFR. Results Median eGFR before tenofovir initiation was 103 (interquartile range, 88–116) ml/min per 1.73 m2. During the first year of tenofovir use, eGFR decreased on average by 9.2 (95% confidence interval, 6.5 to 11.9) ml/min per 1.73 m2 and was stable afterward (decrease of 0.62; 95% confidence interval,-0.85 to 2.1 ml/min per 1.73 m2 per year). After multivariable adjustment, higher baseline β-2-microglobulin, KIM-1, and clusterin were associated with larger first-year eGFR declines, whereas higher baseline uromodulin was associated with a smaller eGFR decline. First-year increase in urinary cystatin C and higher year 1 IL-18 were associated with larger annual eGFR declines from year 1 to year 3. The parsimonious models identified higher pre-tenofovir clusterin and KIM-1, lower pre-tenofovir uromodulin, and higher year 1 IL-18 as jointly associated with larger eGFR declines. Conclusions Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV.
AB - Background and objectives Tenofovir disoproxil fumarate (tenofovir) is associated with elevated concentrations of biomarkers of kidney damage and dysfunction in individuals with HIV. The relationship of these kidney biomarkers with longitudinal kidney function decline is unknown. Design, setting, participants, & measurements We evaluated associations of 14 urinary biomarkers of kidney injury with changes in eGFR among 198 men and women with HIV who initiated tenofovir between 2009 and 2015 in the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study. Urinary biomarkers included albumin-to-creatinine ratio, α-1-microglobulin, β-2-microglobulin, cystatin C, kidney injury molecule-1 (KIM-1), IL-18, neutrophil gelatinase–associated lipocalin (NGAL), clusterin, osteopontin, uromodulin, monocyte chemoattractant protein-1, EGF, trefoil factor 3, and chitinase 3-like protein 1. We used multivariable linear mixed-effect models controlling for demographics, traditional kidney disease risk factors, and HIV-related risk factors to evaluate associations of baseline biomarkers with first-year changes in eGFR, and associations of year 1 and first-year change in biomarkers with changes in eGFR from year 1 to year 3. We used the least absolute shrinkage and selection operator method to identify a parsimonious set of biomarkers jointly associated with changes in eGFR. Results Median eGFR before tenofovir initiation was 103 (interquartile range, 88–116) ml/min per 1.73 m2. During the first year of tenofovir use, eGFR decreased on average by 9.2 (95% confidence interval, 6.5 to 11.9) ml/min per 1.73 m2 and was stable afterward (decrease of 0.62; 95% confidence interval,-0.85 to 2.1 ml/min per 1.73 m2 per year). After multivariable adjustment, higher baseline β-2-microglobulin, KIM-1, and clusterin were associated with larger first-year eGFR declines, whereas higher baseline uromodulin was associated with a smaller eGFR decline. First-year increase in urinary cystatin C and higher year 1 IL-18 were associated with larger annual eGFR declines from year 1 to year 3. The parsimonious models identified higher pre-tenofovir clusterin and KIM-1, lower pre-tenofovir uromodulin, and higher year 1 IL-18 as jointly associated with larger eGFR declines. Conclusions Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV.
UR - http://www.scopus.com/inward/record.url?scp=85053352514&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053352514&partnerID=8YFLogxK
U2 - 10.2215/CJN.01700218
DO - 10.2215/CJN.01700218
M3 - Article
C2 - 30154221
AN - SCOPUS:85053352514
SN - 1555-9041
VL - 13
SP - 1321
EP - 1329
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 9
ER -
