Urine Biomarkers of Kidney Tubule Health and Incident CKD Stage 3 in Women Living With HIV: A Repeated Measures Study
Year: 2021
Type: article
Study design: Observational Study
Abstract: Rationale & Objective Single measurements of urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in HIV infection, but the prognostic value of repeat measurements over time is unknown. Study Design Cohort study. Setting & Participants 647 women living with HIV infection enrolled in the Women's Interagency Health Study. Exposures 14 urinary biomarkers of kidney tubule health measured at 2 visits over a 3-year period. Outcome Incident CKD, defined as estimated glomerular filtration rate (eGFR)<60mL/min/1.73m 2 at two 6-month visits and an average eGFR decline≥3% per year. Analytical Approach We used multivariable generalized estimating equations adjusting for CKD risk factors to evaluate baseline, time-updated, and change-over-time biomarker associations with incident CKD. We compared CKD discrimination between models with and without a parsimoniously selected set of biomarkers. Results During a median 7 years of follow-up, 9.7% (63/647) developed CKD. In multivariable-adjusted analyses, 3 of 14 baseline biomarkers associated with incident CKD. In contrast, 10 of 14 time-updated biomarkers and 9 of 14 biomarkers modeled as change over time associated with incident CKD. Urinary epidermal growth factor (EGF), α 1 -microglobulin (A1M), and albumin were selected using penalized regression methods. In the time-updated model, lower urinary EGF (risk ratio [RR] per 2-fold higher time-updated biomarker levels, 0.69; 95% CI, 0.58-0.81), higher urinary A1M (RR, 1.47; 95% CI, 1.25-1.73), and higher urinary albumin excretion (RR, 1.21; 95% CI, 1.03-1.42) were jointly associated with increased risk for CKD. Compared with a base model (C statistic, 0.75), CKD discrimination improved after adding urinary EGF, A1M, and albumin values across baseline (C=0.81), time-updated (C=0.83), and change-over-time (C=0.83) models ( P <0.01 for all). Limitations Observational design, incident CKD definition limited to eGFR. Conclusions Repeat urinary biomarker measurements for kidney tubule health have stronger associations with incident CKD compared with baseline measurements and moderately improve CKD discrimination in women living with HIV infection.
Source: Kidney Medicine
Institutions: San Francisco VA Medical Center, University of California, San Francisco, San Francisco VA Health Care System, University of California, Davis, Johns Hopkins University, SUNY Downstate Health Sciences University, Georgetown University Medical Center, Albert Einstein College of Medicine, Rush University Medical Center, Rush University, Johns Hopkins Medicine, University of California San Diego
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,400
Funders: Northern California Institute for Research and Education, 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 Human Genome Research Institute, 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, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Center for AIDS Research, University of North Carolina at Chapel Hill
Awards: G1044130170, G1400602301, G1655989834, G183157880, G192128497, G2127051194, G248584506, G2755707676, G2759654445, G311558797, G319781266, G3242306066, G3869857964, G4391827178, G483408255, G5078796989, G5699974340, G5747858550, G6509896931, G693265041, G8653535977, G9000030772, G9000088144, 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, Center for AIDS Research at Emory University, 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, Yale Clinical and Translational Science Award, 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: W3152657433