#2445 Trends in diagnosis, renal progression, and therapeutic impact on survival in AL amyloidosis

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Abstract Background and Aims Progressive renal dysfunction is a hallmark of AL amyloidosis and a key determinant of prognosis. Early diagnosis and effective management strategies are critical to improving outcomes. This single-center retrospective study evaluates the clinical course of 104 patients (64 males, 37 females; mean age 64 ± 13 years) managed at the Regional Center for Amyloidosis at “Ospedale Isola Tiberina—Gemelli Isola,” Rome, Italy. By analyzing diagnostic trends, longitudinal renal and cardiac progression, and therapeutic impact, the study aims to provide comprehensive insights into disease dynamics. Method The time from onset to diagnosis, measured in months, was analyzed using linear and quantile regression models to explore temporal trends. Longitudinal changes in renal function (creatinine, proteinuria, eGFR) and organ scores (RENAL and CARDIAC) were assessed using delta values and paired comparisons (Wilcoxon signed-rank test) at four key time points: onset, diagnosis, one-year follow-up, and two-year follow-up or last available follow-up. Renal involvement was categorized as None, Proteinuria, Nephrotic Syndrome, or CKD, while cardiac involvement was classified as None, Ventricular Hypertrophy, Arrhythmia, or Heart Failure. Kaplan-Meier survival curves stratified patients by renal and cardiac involvement, induction therapy, and initiation of renal replacement therapy (RRT). Renal progression and response rates were evaluated using Palladini and Muchtar criteria across four therapy groups: no treatment (NT), MELD, +BOR, and +DARA. Independent predictors of mortality were identified using Cox proportional hazards regression. Results The median time from onset to diagnosis decreased from 12 months in earlier years to 5 months in more recent diagnoses, reflecting progress in early recognition, though regression analysis revealed no significant temporal trend (P = 0.99). At onset, 33% of patients had CKD, rising to 63% at diagnosis and 80% at follow-up (P < 0.005), underscoring the progressive nature of renal involvement (Fig. 1A). Creatinine increased significantly from 1.2 ± 0.4 mg/dL at onset to 1.9 ± 0.6 mg/dL at diagnosis, with further increases at 1-year (+0.72 mg/dL, P < 0.001) and 2-year follow-ups (+1.64 mg/dL, P < 0.001). Proteinuria increased by +0.88 g/24 h (P = 0.02) between onset and diagnosis but stabilized thereafter, potentially reflecting therapeutic effects. The RENAL SCORE worsened significantly over time, with a median increase of +2 points from diagnosis to follow-up (P < 0.05). Cardiac involvement trends are shown in Fig. 1B. Among therapies, +DARA significantly mitigated renal progression, with the lowest Palladini progression rates (40% at T1–T3) compared to NT (84%) and MELD (69%) (Fig. 1C). Renal responses by Muchtar and Palladini criteria were highest in the +BOR and +DARA groups versus NT (0%), demonstrating the benefits of current regimens (Fig. 1D). Kaplan-Meier survival analysis showed a clear decline in survival with increasing RENAL SCORE, though significance was not reached (P = 0.07) (Fig. 2A). Patients requiring RRT had a dramatically reduced 5-year survival probability (45% vs 65% in non-RRT patients, P < 0.05) (Fig. 2B). Survival curves showed significantly improved outcomes with +DARA (P < 0.05), while NT had the poorest results. +BOR showed intermediate outcomes, highlighting the survival benefit of advanced therapies (Fig. 2C). Cox regression identified RENAL SCORE, RRT, number of organs involved, age at diagnosis, and worsening cardiac involvement as independent predictors of mortality. Conclusion Renal dysfunction is a pivotal factor in the progression and prognosis of AL amyloidosis. Increasing CKD prevalence, rising creatinine levels, and higher renal involvement emphasize the need for early diagnosis and timely therapeutic interventions. Advanced regimens, such as the addition of daratumumab, not only mitigate renal progression but also improve survival outcomes. This study highlights the importance of regular renal monitoring, tailored treatment strategies, and early intervention to optimize long-term management in AL amyloidosis.

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