Association of Urine Biomarkers of Kidney Health with Subclinical Cardiovascular Disease Among Men with and Without HIV

Overview

Journal AIDS

Specialty Infectious Diseases

Date 2023 Oct 20

PMID 37861689

Authors

Mason Lai

Erin Madden

Michael G Shlipak

Rebecca Scherzer

Wendy S Post

Eric Vittinghoff

Sabina Haberlen

Todd T Brown

Steven M Wolinsky

Mallory D Witt

Ken Ho

Alison G Abraham

Chirag R Parikh

Matthew Budoff

Michelle M Estrella

Affiliations

Soon will be listed here.

Abstract

Objective: The aim of this study was to determine whether urine biomarkers of kidney health are associated with subclinical cardiovascular disease among men with and without HIV.

Design: A cross-sectional study within the Multicenter AIDS Cohort Study (MACS) among 504 men with and without HIV infection who underwent cardiac computed tomography scans and had urine biomarkers measured within the preceding 2 years.

Methods: Our primary predictors were four urine biomarkers of endothelial (albuminuria), proximal tubule dysfunction (alpha-1-microglobulin [A1 M] and injury (kidney injury molecule-1 [KIM-1]) and tubulointerstitial fibrosis (pro-collagen-III N-terminal peptide [PIIINP]). These were evaluated for association with coronary artery calcium (CAC) prevalence, CAC extent, total plaque score, and total segment stenosis using multivariable regression.

Results: Of the 504 participants, 384 were men with HIV (MWH) and 120 were men without HIV. In models adjusted for sociodemographic factors, cardiovascular disease risk factors, eGFR, and HIV-related factors, each two-fold higher concentration of albuminuria was associated with a greater extent of CAC (1.35-fold higher, 95% confidence interval 1.11-1.65), and segment stenosis (1.08-fold greater, 95% confidence interval 1.01-1.16). Associations were similar between MWH and men without HIV in stratified analyses. The third quartile of A1 M showed an association with greater CAC extent, total plaque score, and total segment stenosis, compared with the lowest quartile.

Conclusion: Worse endothelial and proximal tubule dysfunction, as reflected by higher urine albumin and A1 M, were associated with greater CAC extent and coronary artery stenosis.

References

DeFilippis A, Kramer H, Katz R, Wong N, Bertoni A, Carr J . Association between coronary artery calcification progression and microalbuminuria: the MESA study. JACC Cardiovasc Imaging. 2010; 3(6):595-604. PMC: 4083743. DOI: 10.1016/j.jcmg.2010.01.008. View

Kramer H, Jacobs Jr D, Bild D, Post W, Saad M, Detrano R . Urine albumin excretion and subclinical cardiovascular disease. The Multi-Ethnic Study of Atherosclerosis. Hypertension. 2005; 46(1):38-43. DOI: 10.1161/01.HYP.0000171189.48911.18. View

Johnson K, Johnson H, Zhao Y, Dowe D, Staib L . Scoring of Coronary Artery Disease Characteristics on Coronary CT Angiograms by Using Machine Learning. Radiology. 2019; 292(2):354-362. DOI: 10.1148/radiol.2019182061. View

Park M, Shlipak M, Vittinghoff E, Katz R, Siscovick D, Sarnak M . Associations of kidney injury markers with subclinical cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Clin Nephrol. 2015; 84(6):358-63. PMC: 4776253. DOI: 10.5414/CN108668. View

Sarnak M, Katz R, Newman A, Harris T, Peralta C, Devarajan P . Association of urinary injury biomarkers with mortality and cardiovascular events. J Am Soc Nephrol. 2014; 25(7):1545-53. PMC: 4073430. DOI: 10.1681/ASN.2013070713. View

Hacioglu Y, Gupta M, Choi T, George R, Deible C, Jacobson L . Use of cardiac CT angiography imaging in an epidemiology study - the Methodology of the Multicenter AIDS Cohort Study cardiovascular disease substudy. Anadolu Kardiyol Derg. 2013; 13(3):207-14. PMC: 3673004. DOI: 10.5152/akd.2013.065. View

Budoff M, Rader D, Reilly M, Mohler 3rd E, Lash J, Yang W . Relationship of estimated GFR and coronary artery calcification in the CRIC (Chronic Renal Insufficiency Cohort) Study. Am J Kidney Dis. 2011; 58(4):519-26. PMC: 3183168. DOI: 10.1053/j.ajkd.2011.04.024. View

Jotwani V, Katz R, Ix J, Gutierrez O, Bennett M, Parikh C . Urinary Biomarkers of Kidney Tubular Damage and Risk of Cardiovascular Disease and Mortality in Elders. Am J Kidney Dis. 2018; 72(2):205-213. PMC: 6057830. DOI: 10.1053/j.ajkd.2017.12.013. View

Triant V, Lee H, Hadigan C, Grinspoon S . Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007; 92(7):2506-12. PMC: 2763385. DOI: 10.1210/jc.2006-2190. View

10.

Ascher S, Scherzer R, Estrella M, Shigenaga J, Spaulding K, Glidden D . HIV preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and changes in kidney function and tubular health. AIDS. 2019; 34(5):699-706. PMC: 7071971. DOI: 10.1097/QAD.0000000000002456. View

11.

Post W, Budoff M, Kingsley L, Palella Jr F, Witt M, Li X . Associations between HIV infection and subclinical coronary atherosclerosis. Ann Intern Med. 2014; 160(7):458-67. PMC: 4143766. DOI: 10.7326/M13-1754. View

12.

Szczech L, Grunfeld C, Scherzer R, Canchola J, van der Horst C, Sidney S . Microalbuminuria in HIV infection. AIDS. 2007; 21(8):1003-9. PMC: 3189480. DOI: 10.1097/QAD.0b013e3280d3587f. View

13.

Reilly M, Wolfe M, Russell Localio A, Rader D . Coronary artery calcification and cardiovascular risk factors: impact of the analytic approach. Atherosclerosis. 2004; 173(1):69-78. DOI: 10.1016/j.atherosclerosis.2003.10.010. View

14.

Sung K, Ryu S, Lee J, Lee S, Cheong E, Hyun Y . Urine Albumin/Creatinine Ratio Below 30 mg/g is a Predictor of Incident Hypertension and Cardiovascular Mortality. J Am Heart Assoc. 2016; 5(9). PMC: 5079007. DOI: 10.1161/JAHA.116.003245. View

15.

Peralta C, Scherzer R, Grunfeld C, ABraham A, Tien P, Devarajan P . Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS). HIV Med. 2013; 15(5):291-300. PMC: 3975680. DOI: 10.1111/hiv.12113. View

16.

Lo J, Abbara S, Shturman L, Soni A, Wei J, Rocha-Filho J . Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS. 2009; 24(2):243-53. PMC: 3154841. DOI: 10.1097/QAD.0b013e328333ea9e. View

17.

Anyanwagu U, Donnelly R, Idris I . Albuminuria Regression and All-Cause Mortality among Insulin-Treated Patients with Type 2 Diabetes: Analysis of a Large UK Primary Care Cohort. Am J Nephrol. 2019; 49(2):146-155. DOI: 10.1159/000496276. View

18.

Go A, Chertow G, Fan D, McCulloch C, Hsu C . Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351(13):1296-305. DOI: 10.1056/NEJMoa041031. View

19.

Choi A, Li Y, Deeks S, Grunfeld C, Volberding P, Shlipak M . Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons. Circulation. 2010; 121(5):651-8. PMC: 2829672. DOI: 10.1161/CIRCULATIONAHA.109.898585. View

20.

Kearns A, Gordon J, Burdo T, Qin X . HIV-1-Associated Atherosclerosis: Unraveling the Missing Link. J Am Coll Cardiol. 2017; 69(25):3084-3098. PMC: 5512584. DOI: 10.1016/j.jacc.2017.05.012. View