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Kidney tubule health scores and their associations with incident CKD in women living with HIV
Author(s) -
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
Publication year - 2021
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/hiv.13081
Subject(s) - medicine , kidney disease , risk factor , urine , reabsorption , kidney , acute kidney injury , confidence interval , beta 2 microglobulin , urology , endocrinology
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.