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

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

Objectives Individual kidney tubule biomarkers are associated with chronic kidney disease (CKD) risk in people living with HIV (PLWH). Whether a combination of kidney biomarkers can be integrated into informative summary scores for PLWH is unknown. Methods We measured eight urine biomarkers of kidne...

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Bibliographic Details
Published in:HIV medicine Vol. 22; no. 7; pp. 527 - 537
Main Authors: Ascher, SB, Scherzer, R, Estrella, MM, Muiru, AN, Jotwani, VK, Grunfeld, C, Shigenaga, J, Spaulding, KA, Ng, DK, Gustafson, D, Spence, AB, Sharma, A, Cohen, MH, Parikh, CR, Ix, JH, Shlipak, MG
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01-08-2021
Subjects:
Albumin
Albumins
Biomarkers
chronic kidney disease
Confidence intervals
Epidermal growth factor
exploratory factor analysis
Factor analysis
Female
Glomerular Filtration Rate
Growth factors
Health risks
HIV
HIV Infections - complications
Human immunodeficiency virus
Humans
Injuries
Interleukins
Kidney
Kidney diseases
Kidney Tubules - injuries
Kidneys
Reabsorption
Renal Insufficiency, Chronic - epidemiology
Risk analysis
Risk Factors
Trefoil factor
Urine
exploratory factor analysis
chronic kidney disease
HIV
biomarkers
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Summary:Objectives Individual kidney tubule biomarkers are associated with chronic kidney disease (CKD) risk in people living with HIV (PLWH). Whether a combination of kidney biomarkers can be integrated into informative summary scores for PLWH is unknown. Methods We measured eight urine biomarkers of kidney tubule health at two visits over a 3‐year period in 647 women living with HIV in the Women's Interagency Health Study. We integrated biomarkers into factor scores using exploratory factor analysis. We evaluated associations between CKD risk factors and factor scores, and used generalized estimating equations to determine associations between factor scores and risk of incident CKD. Results Factor analysis identified two unique factor scores: a tubule reabsorption score comprising alpha‐1‐microglobulin, beta‐2‐microglobulin and trefoil factor‐3; and a tubule injury score comprising interleukin‐18 and kidney injury molecule‐1. We modelled the two factor scores in combination with urine epidermal growth factor (EGF) and urine albumin. Predominantly HIV‐related CKD risk factors were independently associated with worsening tubule reabsorption scores and tubule injury scores. During a median follow‐up of 7 years, 9.7% (63/647) developed CKD. In multivariable time‐updated models that adjusted for other factor scores and biomarkers simultaneously, higher tubule reabsorption scores [risk ratio (RR) = 1.27, 95% confidence interval (CI): 1.01–1.59 per 1 SD higher time‐updated score], higher tubule injury scores (RR = 1.36, 95% CI: 1.05–1.76), lower urine EGF (RR = 0.75, 95% CI: 0.64–0.87), and higher urine albumin (RR = 1.20, 95% CI: 1.02–1.40) were jointly associated with risk of incident CKD. Conclusions We identified two novel and distinct dimensions of kidney tubule health that appear to quantify informative metrics of CKD risk in PLWH.
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Research idea and study design: S.B.A., R.S., M.M.E., M.G.S.; data acquisition: J.S., K.A.S., D.K.N., D.G., A.B.S., A.S., M.H.C.; data analysis/interpretation: S.B.A., R.S., M.M.E., A.N.M., C.G., V.K.J, C.R.P, J.H.I., M.G.S.; statistical analyses: R.S.; supervision or mentorship: M.G.S. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author’s own contributions, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
Author Contributions
ISSN:1464-2662
1468-1293
1468-1293
DOI:10.1111/hiv.13081