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 MACS/WIHS Combined Cohort Study. Cases developed rapid kidney function decline (RKFD: ≥30% eGFR reduction). We measured plasma biomarkers of tubular injury (KIM-1), inflammation (TNFr1, TNFr2), and synthetic function (UMOD, EGF) at baseline and year 2. Associations with RKFD were assessed using multivariable risk regression, adjusting for 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. non-cases (93 vs. 94 mL/min/1.73m 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%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.