Mediation analysis of chronic kidney disease risk factors using kidney biomarkers in women living with HIV
Year: 2024
Type: article
Abstract: OBJECTIVE: Novel urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in persons living with HIV. However, it is unknown whether these biomarkers provide mechanistic insight into the associations between clinical risk factors for CKD and subsequent CKD risk. METHODS: Among 636 women living with HIV in the Women's Interagency HIV Study with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m 2 , we used a counterfactual approach to causal mediation analysis to evaluate the extent to which systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin a1c (Hba1c) and serum albumin associations with incident CKD were mediated by eight urine proteins. These biomarkers reflect proximal tubular reabsorptive dysfunction (α1-microglobulin [a1m], β2-microglobulin, trefoil factor 3); tubular injury (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1]); kidney repair (epidermal growth factor); tubular reserve (uromodulin); and glomerular injury (urinary albumin). Incident CKD was defined as eGFR <60 ml/min/1.73 m 2 measured at two consecutive 6-month visits with an average annual eGFR decline ≥3% per year. RESULTS: During a median follow-up of 7 years, 11% developed CKD. Urinary albumin and KIM-1 mediated 32% (95% CI: 13.4%, 76.6%) and 23% (6.9%, 60.7%) of the association between SBP and incident CKD, respectively; and 19% (5.1%, 42.3%) and 22% (8.1%, 45.7%) of the association between DBP and incident CKD, respectively. Urinary albumin, α1m, and IL-18 were significant mediators of the association between Hba1c and incident CKD. None of the eight biomarkers mediated the association between serum albumin and incident CKD. CONCLUSIONS: Among women living with HIV, several urinary biomarkers reflecting distinct dimensions of kidney health may partially explain the associations between SBP, DBP, and Hba1c and subsequent CKD risk.
Source: AIDS
Institutions: San Francisco VA Medical Center, University of California, San Francisco, San Francisco VA Health Care System, SUNY Downstate Health Sciences University, University of Southern California, Albert Einstein College of Medicine, John H. Stroger, Jr. Hospital of Cook County, Cook County Health and Hospitals System, Georgetown University, University of North Carolina at Chapel Hill, University of Colorado Denver, University of California Davis Medical Center, University of California, Davis
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, American Heart Association, Northern California Institute for Research and Education, Georgia Clinical and Translational Science Alliance, National Institutes of Health, University of California, San Francisco, Center for AIDS Research, University of Alabama at Birmingham, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Nursing Research, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities, Center for AIDS Research, University of North Carolina at Chapel Hill, Clinical and Translational Science Institute, University of California, Los Angeles
Awards: G1034546755, G12089860, G1296759572, G1400602301, G156123175, G1655989834, G1773452051, G1787625665, G183157880, G1849940085, G1913134163, G192128497, G2008237588, G2127051194, G2334180555, G248584506, G255204022, G2755707676, G2759654445, G2826625206, G2839061624, G2908277772, G30074556, G311558797, G319781266, G3242306066, G3418878615, G343705321, G3630727822, G3671922257, G3869857964, G4016133911, G4044828089, G4391827178, G4535678174, G456742281, G4645810025, G483408255, G5078796989, G5198004604, G521591464, G526943639, G5431849782, G5525419549, G5691055145, G5747858550, G5900455136, G6727567258, G6745172908, G693265041, G6990385686, G7140729675, G775892330, G7807729167, Johns Hopkins Institute for Clinical and Translational Research, Incorporating Patient Outcome Preferences into Personalized Blood Pressure Target Decisions, G9000016284, G9000025022, G9000030090, G9000030772, G9000031392, G9000036510, G9000039899, G9000041916, G9000080293, G9000082816, G9000102070, G9000108991, G9000146713, University of Pittsburgh MACS/WIHS CCS, MACS/WIHS -CCS, UNC MACS/WIHS Combined Cohort Study Clinical Research Site, Surviving the HIV Epidemic (S/HE) in metropolitan Washington DC - Advancing knowledge through cohort studies, Biomarker-Based Diagnostic Algorithms To Prevent, Detect And Guide Treatment Of Kidney Disease In Persons Living With HIV, Institutional Career Development Core (KL2), Data Analysis and Coordination Center for the MACS-WIHS Combined Cohort Study, MACS/WIHS Combined Cohort Study: Brooklyn Clinical Research Site (Bklyn CRS), Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS) - Baltimore/Wash DC Center, UAB-MISS MACS/WIHS Combined Cohort Study, Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS), UAB Center for AIDS Research (CFAR)
OpenAlex ID: W4390876516