Associations of repeated measures of plasma biomarkers of kidney tubular health with longitudinal kidney function in people with HIV.

BACKGROUND

In people with HIV (PWH), urine tubular biomarkers have been linked to kidney function decline, but urine concentration variability limits their clinical utility. Plasma biomarkers may offer more stable indicators of kidney tubular health.

METHODS

We conducted a case-cohort study of 440 PWH from the Multicenter AIDS Cohort Study (MACS)/Women's Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS). Cases developed rapid kidney function decline [RKFD: ≥30% estimated glomerular filtration rate (eGFR) reduction]. We measured plasma biomarkers of tubular injury [kidney injury molecule-1 (KIM-1)], inflammation [tumor necrosis factor receptor-1 (TNFr1) and tumor necrosis factor receptor-2 (TNFr2)], and synthetic function [uromodulin (UMOD) and epidermal growth factor (EGF)] at baseline and year 2. Associations with RKFD were assessed using multivariable risk regression, adjusting for chronic kidney disease (CKD) and HIV-related risk factors, eGFR, and albuminuria. In a random sub-cohort, linear mixed models evaluated associations with annualized eGFR change.

RESULTS

At baseline, median age was 49 years; 33% were women; 69% were virally suppressed; eGFR was similar in cases vs. noncases (93 vs. 94 ml/min/1.73 m 2 ). Over a median of 4.5 years, 172 RKFD events occurred. Each 1-standard deviation higher baseline KIM-1, TNFr1, TNFr2, UMOD, and EGF level was associated with adjusted relative risks (RR) for RKFD of 1.26 [95% confidence interval (CI): 1.15-1.39], 1.39 (1.24-1.55), 1.40 (1.24-1.57), 0.84 (0.77-0.93), and 0.85 (0.78-0.92), respectively. Findings were similar at year 2 and for 2-year biomarker changes. In joint models, baseline KIM-1, TNFr2, and UMOD remained independently associated with RKFD [RR: 1.19 (1.08-1.31), 1.27 (1.12-1.43), and 0.86 (0.78-0.95)], respectively. No biomarker was associated with annualized eGFR change in the sub-cohort.

CONCLUSION

In PWH, plasma biomarkers reflecting impaired kidney tubular health were independently associated with RKFD and may be useful prognosticators of adverse kidney outcomes.