Kidney disease risk factors associate with urine biomarkers concentrations in HIV-positive persons; a cross-sectional study

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.Electronic supplementary materialThe online version of this article (10.1186/s12882-018-1192-y) contains supplementary material, which is available to authorized users.

Associations of CKD risk factors and longitudinal changes in urine biomarkers of kidney tubules among women living with HIV

“…Findings from this analysis are in line with our prior cross-sectional study [ 26 ], and extend our earlier observations to longitudinal analyses, which allow for much stronger inferences. For instance, serum albumin is strongly predictive of mortality among PLWH [ 40 – 42 ], and the importance of serum albumin in our study was reflected by the association of both baseline and changes in serum albumin with biomarkers of tubular reabsorptive dysfunction, immune response and tubular reserve.…”

“…Ultimately, we envision using this information to develop parsimonious algorithms that integrate longitudinal changes in biomarker levels with clinical data to better detect and manage kidney disease. However, most studies to date have predominantly examined the association of CKD risk factors with biomarkers cross-sectionally [ 26 – 30 ]. To advance the kidney biomarker research field forward we need to ascertain whether these risk factors contribute to changes in the biomarkers over time.…”

Kidney tubule health scores and their associations with incident CKD in women living with HIV

“…A previous study among CKD participants in the Systolic Blood Pressure Intervention Trial (SPRINT) used factor analysis to combine 10 kidney biomarkers into four distinct factors, and found that each factor score had independent associations with cardiovascular disease, heart failure and death, and also improved event prediction [19]. Over the previous decade, we have demonstrated that several kidney tubule biomarkers are elevated in PLWH compared with uninfected individuals; reflect different CKD risk factor profiles; predict eGFR decline following TDF initiation; independently associate with eGFR decline and mortality risk; and have stronger associations with CKD risk when the biomarker measures are repeated over time [12][13][14][15][16][17]21,22,[26][27][28]. However, interpreting a large number of novel kidney biomarkers would be challenging for the clinician.…”

“…We also excluded urine EGF from the factor analysis because its factor loading was in the opposite hypothesized direction from its CKD association. However, because of the strength of association of urine EGF with CKD in our prior work, we retained it in the final multivariable models as a separate measure [21,22]. A model with two factors was determined to be the best solution for the remaining five biomarkers.…”

Eradicating the Viral Triad in Hemodialysis Units

“…To this point, in 2 longitudinal, prospective, observational HIV studies of men and women, Multicenter Acquired Immunodeficiency Syndrome (AIDS) Cohort Study and Women's Interagency HIV Study, only one-third of 198 participants were on an HAART regimen that did not include nephrotoxic tenofovir disoproxil fumarate. 11 Currently, because of the success of HAART, HIV treatment is mostly out of nephrologists' hands now. Likely, the most crucial knowledge for the nephrologists may be recognition of agents that require renal-dosing adjustments.…”