Abstract
BackgroundHIV-positive persons bear an excess burden of chronic kidney disease (CKD); however, conventional methods to assess kidney health are insensitive and non-specific for detecting early kidney injury. Urinary biomarkers can detect early kidney injury, and may help mitigate the risk of overt CKD.MethodsCross-sectional study of HIV-positive persons in the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study. We measured levels of 14 biomarkers, capturing multiple dimensions of kidney injury. We then evaluated associations of known CKD risk factors with urine biomarkers using separate multivariable adjusted models for each biomarker.ResultsOf the 198 participants, one third were on HAART and virally suppressed. The vast majority (95%) had preserved kidney function as assessed by serum creatinine, with a median eGFR of 103 ml/min/1.73 m2 (interquartile range (IQR): 88, 116). In our multivariable analyses, the associations of each CKD risk factor with urinary biomarker levels varied in magnitude. For example, HIV viral load was predominantly associated with elevations in interleukin(IL)-18, and albuminuria, while higher CD4 levels were associated with lower monocyte chemoattractant protein-1 (MCP-1) and β2-microglobulin. In contrast, older age was significantly associated with elevations in α1-microglobulin, kidney injury marker-1, clusterin, MCP-1, and chitinase-3-like protein-1 levels, as well as lower epidermal growth factor, and uromodulin levels.ConclusionsAmong HIV-positive persons, CKD risk factors are associated with unique and heterogeneous patterns of changes in urine biomarkers levels. Additional work is needed to develop parsimonious algorithms that integrate multiple biomarkers and clinical data to discern the risk of overt CKD and its progression.
Highlights
human immunodeficiency virus (HIV)-positive persons bear an excess burden of chronic kidney disease (CKD); conventional methods to assess kidney health are insensitive and non-specific for detecting early kidney injury
To evaluate whether each CKD risk factor has a distinct pattern of kidney injury, we examined their associations with a panel of urine biomarkers of kidney injury among HIV-positive individuals who were not on tenofovir disoproxil fumarate (TDF) in the Multicenter AIDS Cohort Study (MACS) and the Women’s Interagency HIV Study (WIHS)
Median CD4+ count was 483 cells/mm3 ([Interquartile range (IQR)]: 338, 682), 29% of persons had undetectable HIV viral load (HIV RNA < 80 copies/mL), 33% were on ART, 48% were hypertensive, 17% had diabetes, and 17% were co-infected with hepatitis C virus (HCV)
Summary
HIV-positive persons bear an excess burden of chronic kidney disease (CKD); conventional methods to assess kidney health are insensitive and non-specific for detecting early kidney injury. The improved life expectancy among treated HIV-positive patients has been tempered by the excess burden of age-related non-infectious co-morbidities, including chronic kidney disease (CKD) [1,2,3] In this population, CKD results from traditional risk factors, such (2019) 20:4 overt CKD and its consequences. A set of complementary urinary biomarkers, rather than a single biomarker, is likely needed to capture these multiple dimensions of kidney injury and to distinguish the site-specific risk factors within the nephron Levels of these biomarkers would prognosticate CKD risk, and inform clinical decision-making in a variety of clinical settings encountered in the care of HIV-positive persons [16, 27]
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