Urine Biomarkers of Kidney Tubule Health and Incident CKD Stage 3 in Women Living With HIV: A Repeated Measures Study

Simon B Ascher; Rebecca Scherzer; Michelle M Estrella; Vasantha K Jotwani; Judy Shigenaga; Kimberly A Spaulding; Derek K Ng; Deborah Gustafson; Amanda B Spence; Anjali Sharma; Mardge H Cohen; Chirag R Parikh; Joachim H Ix; Michael G Shlipak

doi:10.1016/j.xkme.2021.01.012

Urine Biomarkers of Kidney Tubule Health and Incident CKD Stage 3 in Women Living With HIV: A Repeated Measures Study

Kidney Med. 2021 Apr 17;3(3):395-404.e1. doi: 10.1016/j.xkme.2021.01.012. eCollection 2021 May-Jun.

Authors

Affiliations

¹ Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, San Francisco, CA.
² Department of Medicine, University of California, Davis, Sacramento, CA.
³ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
⁴ Department of Neurology, The State University of New York Downstate Health Sciences University, Brooklyn, NY.
⁵ Division of Infectious Diseases, Department of Medicine, Georgetown University Medical Center, Washington, DC.
⁶ Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
⁷ Department of Medicine, Stroger Hospital and Rush University, Chicago, IL.
⁸ Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
⁹ Division of Nephrology-Hypertension, University of California, San Diego, San Diego, CA.

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) < 60 mL/min/1.73 m² 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), α₁-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.

Keywords: Chronic kidney disease; HIV; albuminuria; epidermal growth factor; α-1 microglobulin.

Abstract

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