New-Onset Proteinuria (NOP) During Hospitalization: A Critical Prognostic Marker in Atherosclerotic Cardiovascular Disease, Reports JACC Advances

Atherosclerotic cardiovascular disease (ASCVD), encompassing ischemic heart disease and cerebrovascular disease (mainly ischemic stroke), remains the leading cause of global mortality. Improving the prognosis of these patients requires identifying and initiating early intervention for prognostic risk factors.

Proteinuria is a recognized independent predictor of adverse outcomes in patients with ASCVD. While urinary protein is routinely screened at admission, most previous studies have focused only on patients with pre-existing proteinuria, which largely reflects underlying chronic kidney disease (CKD). Consequently, evidence regarding the prognostic value of new-onset proteinuria (NOP) during hospitalization in ASCVD patients who were negative for proteinuria at admission has been lacking.

Study Overview

This observational cohort study aimed to address this gap by examining the associations between NOP during hospitalization and the risks of cardiovascular (CV) mortality and composite adverse kidney outcomes after discharge.

This multicenter, retrospective cohort study used data from the China Renal Data System, covering 24 academic hospitals. It included hospitalized adults with ASCVD who had no proteinuria at admission. Patients with a positive initial urine protein test, baseline eGFR <60 mL/min/1.73 m², or prior ESRD were excluded. New-onset proteinuria was defined as a urine dipstick change from negative to ≥1+ during hospitalization. The primary outcome was cardiovascular mortality after discharge, identified through the national cause-of-death registry. The secondary outcome was a composite of kidney events, including sustained eGFR <60 mL/min/1.73 m², >40% eGFR decline, or ESRD.

Key Findings

The nationwide cohort included 34,429 inpatients with a mean age of 64 years. New-onset proteinuria occurred in 7.5% of this population during hospitalization. Risk factors for NOP included Acute Kidney Injury (AKI) (highest incidence at 23.8%), ICU admission, surgery, and elevated systolic blood pressure (SBP), while higher serum albumin was protective.

During a mean follow-up of 4.6 years, CV mortality occurred in 13.77% of patients with new-onset proteinuria compared with 7.49% of those without it.

After adjusting for confounders, new-onset proteinuria was linked to a higher risk of CV mortality and adverse kidney outcomes compared with patients who did not develop proteinuria during hospitalization.

The prognostic value remained significant even after excluding patients with AKI, demonstrating the independent link of NOP to adverse outcomes. Furthermore, the risk associated with NOP was amplified in specific subgroups, notably in patients with diabetes and chronic heart failure.

Clinical Implications

The findings underscore that the presence of NOP during hospitalization among ASCVD patients possesses significant prognostic value and should be carefully monitored to improve patient care.

The independent association between NOP and CV mortality, separate from AKI, suggests that acute changes in urinary protein should gain more attention in clinical practice. Mechanistically, proteinuria reflects systemic endothelial dysfunction or subclinical renal disease, which accelerates ASCVD progression. Clinicians can use the readily available urinary protein data to enhance risk stratification for long-term health.

Reference: Su L, Chen R, Zhou S, Guo Z, Li Y, Zhang X, Luo F, Gao Q, Lin Y, Cao L, Liu J, Pang M, She C, Xu X, Nie S. Association Between New-Onset Proteinuria During Hospitalization and Cardiovascular Mortality Among Patients With Atherosclerotic Cardiovascular Disease. JACC Adv. 2025 Nov 5;4(12 Pt 2):102279. doi: 10.1016/j.jacadv.2025.102279. Epub ahead of print. PMID: 41197562.

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