The Cardiorenal Nexus in ATTR-Amyloidosis: Enhanced Risk Stratification beyond estimated glomerular filtration rate (eGFR)
M Eslami, N Ermolaev, L Schmidt, M Poledniczek, S Pahr, D Ahmadi-Fazel, R Badr EslamAbstract
Background/Introduction
Transthyretin amyloid cardiomyopathy (ATTR-CM) staging using the National Amyloidosis Centre (NAC) system relies on NT-proBNP and eGFR levels. However, eGFR is a late marker of renal dysfunction and may miss early structural kidney damage. The heart and kidney form a delicate cardiorenal axis, in which structural damage, as reflected in the urine albumin-to-creatinine ratio (UACR), often precedes a decline in eGFR. Relying solely on eGFR risks misclassifying early-stage ATTR-CM patients as "low risk" despite significant glomerular damage. According to KDIGO 2024 guidelines, comprehensive renal risk assessment requires evaluating both filtration capacity and structural damage.
Purpose
We aimed to evaluate the comprehensive renal burden in an ATTR-CM cohort by assessing the incremental diagnostic value of UACR beyond eGFR in identifying early cardiorenal risk.
Method
A retrospective longitudinal study was conducted in 124 patients with biopsy- or scintigraphy-confirmed transthyretin amyloid cardiomyopathy (ATTR CM). Clinical, biochemical, and renal parameters were collected at baseline and at follow-up visits. Renal structural damage was assessed using the UACR, and renal filtration capacity using the eGFR. The longitudinal cardiorenal correlation between myocardial stress, assessed by NT-proBNP levels, and structural glomerular damage, assessed by UACR, was evaluated. All parameters were assessed at baseline and 12-month follow-up using Spearman’s rank correlation, with statistical significance defined as p < 0.05.
Results
The cohort included 124 patients with ATTR-CM (median age 80.2 years, 88.7% male). At baseline, patients had a median eGFR of 61.2 mL/min/1.73 m² and a median UACR of 18.4 mg/g. The population was distributed across NAC stages I (58%), II (31%), and III (11%), with a median NT-proBNP of 2450 pg/mL. The cross-sectional analysis at baseline demonstrated a continuous, positive correlation between NT-proBNP level and UACR (Spearman’s rho = 0.45, p < 0.001). As illustrated in Figure 1, stratification by clinical cardiac severity revealed that while NAC Stage III patients consistently exhibited high UACR, a substantial proportion of clinically "low-risk" NAC Stage I patients also demonstrated significant pathological protein leakage. This visualizes early cardiorenal axis activation, showing that structural kidney compromise often precedes advanced clinical cardiac staging. At 12-month follow-up, the positive longitudinal correlation between NT-proBNP level and UACR remained robust and highly significant (Spearman’s rho = 0.50, p < 0.001).
Conclusion
Relying solely on eGFR in ATTR-CM overlooks early structural kidney damage, which is frequently present even in NAC Stage I patients. These findings highlight the importance of incorporating albuminuria into risk assessment frameworks for ATTR CM.Figure 1