TY - JOUR
T1 - Tubular Secretory Solute Clearance and HIV Infection
AU - Garimella, Pranav S.
AU - Scherzer, Rebecca
AU - Kestenbaum, Bryan R.
AU - Hoofnagle, Andrew N.
AU - Jotwani, Vasantha
AU - Gustafson, Deborah
AU - Karim, Roksana
AU - Sharma, Anjali
AU - Cohen, Mardge
AU - Dumond, Julie
AU - Abraham, Alison
AU - Estrella, Michelle
AU - Shlipak, Michael G.
AU - Ix, Joachim H.
N1 - Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - 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.
AB - 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.
KW - HIV
KW - biomarker
KW - clearance
KW - kidney tubule
KW - secretion
KW - women
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U2 - 10.1097/QAI.0000000000003200
DO - 10.1097/QAI.0000000000003200
M3 - Article
C2 - 36988544
AN - SCOPUS:85164055808
SN - 1525-4135
VL - 93
SP - 319
EP - 326
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 4
ER -