Development and Validation of Staging Systems for AA Amyloidosis

Background: The kidney is involved in almost 100% of cases of AA amyloidosis, a rare disease caused by persistent inflammation with long overall survival but frequent progression to end-stage kidney failure . Identification of patients with advanced disease at diagnosis is difficult, given the absence of validated staging systems. Methods: Newly diagnosed patients with AA amyloidosis from the Pavia (n=233, testing cohort) and Heidelberg (n=243, validation cohort) centers were included in the study. Cut-offs of continuous variables were determined by ROC analysis predicting death or dialysis at 24 months. Prognostic factors included in staging systems were identified by multivariable models in the testing cohort. Results: Age >= 65 years, estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m(2) and elevated natriuretic peptides (type-B natriuretic peptide [BNP] >130 ng/L and/or N-terminal BNP [NT-proBNP] >1000 ng/L) were predictors of overall survival and included in the staging system (all with simplified coefficients 1). Mean 36-months overall survival was lower with higher staging system scores (score 0-1: 92%; score 2: 72%; score 3: 32%). These results were confirmed in the validation cohort. For kidney failure, variables selected to enter in the staging system model were proteinuria >3 g/24h and eGFR <35 mL/min/1.73m(2) (both with simplified coefficients 1). The 36-month cumulative incidence of kidney failure was higher with higher staging system scores (score 0: 0%; score 1: 24%; score 2: 51%). Again, similar results were obtained in validation cohort. Conclusions: We identified and validated biomarker-based staging systems for overall survival and kidney failure in AA amyloidosis.