Isolated Non-Albumin Proteinuria Was Associated with the Progression of Chronic Kidney Disease in Hypertensive Patients: A Retrospective Cohort Study

OBJECTIVES: Isolated non-albumin proteinuria (iNAP) has been linked to kidney function decline in diabetes, but its prognostic role in hypertensive patients with chronic kidney disease (CKD) and normal albuminuria remains uncertain. We evaluated whether baseline iNAP predicts longitudinal estimated glomerular filtration rate (eGFR) decline and kidney events in this setting. METHODS: In a retrospective cohort of 166 hypertensive CKD outpatients with normal albuminuria, iNAP was defined as total 24-h proteinuria ≥150 mg/day with albuminuria <30 mg/day. Kidney function change was assessed as (i) eGFR trajectory over 6 years using linear mixed-effects models and (ii) a composite kidney endpoint (≥30% eGFR decline or incident end-stage kidney disease) using cumulative incidence and Fine-Gray competing-risk regression (death as competing event). Confounding control was guided by a directed acyclic graph (DAG), yielding a minimal adjustment set (age, sex, diabetes, on-treatment mean arterial pressure, baseline eGFR). Sensitivity analyses examined alternative model specifications and endpoint definitions. RESULTS: Median follow-up was 5.4 years (interquartile range 4.5-6.0). iNAP was present in 41/166 participants; 32 reached the composite kidney endpoint and 25 died. Baseline eGFR was similar in iNAP versus normal proteinuria (57 ± 24 vs. 61 ± 24 mL/min/1.73 m2; p = 0.318). In mixed-effects models, eGFR declined by -0.61 mL/min/1.73 m2/year (95% confidence interval [CI]: -0.96 to -0.25) in normal proteinuria and by -1.53 mL/min/1.73 m2/year (95% CI: -2.15 to -0.91) in iNAP, with a between-group slope difference of -0.92 mL/min/1.73 m2/year (95% CI: -1.63 to -0.22; time × iNAP interaction p = 0.011). In competing-risk analyses, iNAP was associated with a higher risk of the composite kidney endpoint (Fine-Gray subdistribution hazard ratio 3.15, 95% CI: 1.58-6.31; p = 0.001), while cumulative incidence of death without prior kidney endpoint (the competing event) did not differ between groups (Gray's test p = 0.920). Findings were consistent after DAG-minimal adjustment and across sensitivity analyses. CONCLUSIONS: In hypertensive CKD patients with normal albuminuria, baseline iNAP is associated with faster eGFR decline and a higher risk of kidney events, independent of key baseline risk factors in DAG-guided analyses.