Association of Low-Grade Proteinuria with Arterial Stiffness in Early-Stage Autosomal Dominant Polycystic Kidney Disease

Objective: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic ciliopathy characterized by progressive renal cyst formation and an increased risk of early cardiovascular morbidity. Arterial stiffness has been demonstrated in ADPKD even before the development of hypertension. However, the independent contribution of low-grade proteinuria to vascular dysfunction in normotensive patients with preserved renal function remains insufficiently characterized. We aimed to evaluate the association between proteinuria and arterial stiffness parameters in normotensive patients with early-stage ADPKD.Methods: In this cross-sectional case–control study, 20 normotensive ADPKD patients and 19 healthy controls were included. Individuals with diabetes mellitus, smoking history, cardiovascular disease, or antihypertensive medication use were excluded. Arterial stiffness parameters, including pulse wave velocity (PWV) and augmentation index (AIx), were assessed using an oscillometric device. ADPKD patients were stratified according to 24-hour urinary protein excretion: non-proteinuric (<150 mg/day) and proteinuric (150–1000 mg/day).Results: ADPKD patients exhibited significantly higher PWV compared to controls [5.95 (4.0–8.5) vs. 5.15 (3.85–7.95) m/s; p=0.041], while AIx values were comparable (p=0.477). In the subgroup analysis, the proteinuric ADPKD group (n=13) showed significantly increased arterial stiffness and wave reflection compared to the non-proteinuric group (n=7) (PWV: 6.35 vs. 5.05 m/s, p=0.021; AIx: 32.1 vs. 23.7, p=0.032). Importantly, these vascular alterations in the proteinuric subgroup were observed despite comparable eGFR levels between the two ADPKD subgroups (p>0.05), indicating that vascular impairment in early ADPKD may be independent of significant renal function decline.Conclusion: Arterial stiffness is increased in normotensive patients with early-stage ADPKD, independent of hypertension. Moreover, even low-grade proteinuria (150-1000 mg/day) is associated with greater impairment in both large-artery stiffness and peripheral wave reflection parameters. These findings suggest that proteinuria may serve as an early marker of subclinical vascular dysfunction in ADPKD.