title: Association of HIV infection with biomarkers of kidney injury and fibrosis in the Multicenter AIDS Cohort Study.
abstract: Chronic kidney disease (CKD) is common among HIV-infected individuals but serum creatinine is insensitive for detecting kidney damage at early stages. We hypothesized that HIV infection would be associated with elevations in subclinical markers of kidney injury and fibrosis in a contemporary cohort of men.
  
  
  
  In this cross-sectional study, we measured urine levels of interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), pro-collagen type III N-terminal pro-peptide (PIIINP) and albumin-creatinine ratio (ACR) in 813 HIV-infected and 331 uninfected men enrolled in the Multicenter AIDS Cohort Study.
  
  
  
  Median eGFR was 95 ml/min/1.73 m2among African-Americans (n=376) and 87 ml/min/1.73 m2among Caucasians (n=768). Among HIV-infected men, the median CD4 lymphocyte count was 572 cells/mm3and 76% of men had undetectable HIV RNA levels. After multivariable adjustment for traditional CKD risk factors including eGFR, HIV infection was associated with 52% higher urine IL-18 (95% CI, 33%, 73%), 44% higher KIM-1 (27%, 64%), 30% higher PIIINP (15%, 47%) and 84% higher ACR (54%, 120%), with similar effect sizes among African-Americans and Caucasians (P>0.2 for tests of interaction by race). These associations remained statistically significant in analyses that excluded persons with detectable HIV RNA levels and in models that adjusted for cumulative exposure to tenofovir disoproxil fumarate.
  
  
  
  Compared with uninfected men, HIV-infected men had more extensive glomerular and tubulointerstitial damage, as assessed by urine biomarkers. Future studies should evaluate whether combinations of biomarkers can be used to monitor stages of kidney injury and to predict CKD risk in HIV-infected individuals.
authors.affiliation: Department of Medicine, San Francisco VA Medical Center, San Francisco, CA, USA.|Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco, CA, USA.
authors.forename: Vasantha
authors.initials: V
authors.lastname: Jotwani
authors.affiliation: Department of Medicine, San Francisco VA Medical Center, San Francisco, CA, USA.|Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco, CA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.affiliation: Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Estrella
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.affiliation: Division of HIV Medicine, Department of Medicine, Harbor-UCLA Medical Center and the Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA, USA.
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Witt
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Palella
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Ho
authors.affiliation: Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.affiliation: Section of Nephrology, Department of Medicine, Yale University, New Haven, CT, USA.|Program of Applied Translational Research, Yale University, New Haven, CT, USA.
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
authors.affiliation: Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, CA, USA.|Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Department of Medicine, San Francisco VA Medical Center, San Francisco, CA, USA.|Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Shlipak
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005355:Fibrosis; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016482:Urinalysis; D044465:White People
chemical_list: D015415:Biomarkers