Work

Cardiorenal Nexus in ATTR-Amyloidosis: Beyond eGFR—Leveraging Albuminuria for Enhanced Risk Stratification

Year: 2026

Type: preprint

Abstract: Background Transthyretin amyloid cardiomyopathy (ATTR-CM) leads to progressive heart failure and renal congestion. Existing risk models, such as the National Amyloidosis Centre (NAC) staging system, rely on the estimated glomerular filtration rate (eGFR), which typically identifies organ damage only at advanced stages. In this study, the urine albumin-to-creatinine ratio (UACR) was evaluated as an early marker of systemic disease and its predictive value for disease progression before a decline in eGFR was assessed. Methods In this longitudinal study, 124 patients with ATTR-CM were evaluated using the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Risk Matrix. A statistical model was developed to examine the direct and indirect relationships of baseline UACR and eGFR with subsequent NAC stage and follow-up eGFR. Results The cohort (median age, 80.2 years; 88.7% male) had a median baseline eGFR of 61.2 mL/min/1.73 m 2 and a wide range of UACR values. Generalised structural equation modelling indicated that baseline UACR was not directly associated with follow-up eGFR ( p = 0.971) but was positively associated with subsequent NAC stage ( p = 0.068). Follow-up eGFR exhibited a strong correlation with NAC stage ( p < 0.001). At a preserved eGFR of 60 mL/min/1.73 m 2 , increasing the UACR from 30 to 400 mg/g reduced the probability of remaining in NAC Stage I from 76.6% to 41.3%, whereas the likelihood of progression to NAC Stage II increased from 23.2% to 56.7%. Conclusions UACR serves as a sensitive early indicator of systemic disease in ATTR-CM. Incorporating UACR alongside eGFR facilitates earlier detection of subclinical cardiac and renal involvement, potentially improving risk stratification and supporting more timely therapeutic intervention before irreversible organ damage occurs.

Source: Research Square

DOI: 10.21203/rs.3.rs-10950422/v1