Tubular Secretory Solute Clearance and HIV Infection

Author:

Garimella Pranav S.1ORCID,Scherzer Rebecca2,Kestenbaum Bryan R.3,Hoofnagle Andrew N.4,Jotwani Vasantha25,Gustafson Deborah6,Karim Roksana7,Sharma Anjali8,Cohen Mardge9,Dumond Julie10,Abraham Alison11,Estrella Michelle25,Shlipak Michael G.25,Ix Joachim H.112

Affiliation:

1. Kidney Research Innovation Hub of San Diego and Division of Nephrology and Hypertension, University of California, San Diego, San Diego;

2. Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco;

3. Kidney Research Institute, Seattle, WA;

4. Department of Laboratory Medicine, University of Washington, Seattle, WA;

5. Department of Medicine, San Francisco VA Medical Health Care System, San Francisco;

6. Department of Neurology, SUNY Downstate Medical Center, New York, NY;

7. Department of Clinical Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA;

8. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY;

9. Stroger Hospital of Cook County Health and Human Services, Chicago, IL;

10. Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Chapel Hill, Chapel Hill, NC;

11. Department of Epidemiology, University of Colorado School of Public Health, Denver, CO; and

12. Veterans Affairs San Diego Healthcare System, San Diego, CA.

Abstract

Background:Tubular secretion is an important kidney function responsible for the clearance of numerous medications, including antibiotics and antivirals. It is unknown whether persons living with HIV have lower secretion compared with HIV-uninfected persons, which might predispose them to the risk of progressive kidney disease or adverse drug events.Setting and Methods:We evaluated a panel of 6 endogenous secretory solutes in 199 women living with HIV (WLWH) and 100 women without HIV enrolled in the Women's Interagency HIV Study. Secretory clearance was estimated as the urine-to-plasma ratio of each solute, with adjustment for urine tonicity. Using multivariable linear regression analysis, we compared differences in levels of secretory solute clearance between women with and without HIV and evaluated characteristics associated with secretion.Results:WLWH were older (median 40 vs. 38 years) but had similar estimated glomerular filtration rate (eGFR, 96 vs. 100 mL/minute/1.73 m2) compared with those without HIV. African American and Latino race, diabetes, diastolic blood pressure, smoking, hepatitis C, peak HIV viral load, and current and nadir CD4 count were associated with differences in clearance of at least 1 marker after multivariable adjustment. The secretory clearance of 3 solutes (cinnamoylglycine, kynurenic acid, and pyridoxic acid) were on average 10%–15% lower among WLWH compared with those without HIV independent of eGFR, albuminuria and chronic kidney disease risk factors, including HCV, and injection drug use.Conclusions:HIV is associated with reduced secretion among women with preserved eGFR. The implications of these findings for drug dosing and adverse events need to be evaluated.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Pharmacology (medical),Infectious Diseases

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