Lessons from four decades of systemic amyloidosis with renal involvement

Abstract

Background: Apart from ATTR amyloidosis, the epidemiology and outcomes of the most common subtypes of systemic amyloidosis in Portugal remain primarily unknown. Methods: This retrospective cohort study evaluated patients with renal biopsy-proven amyloidosis, diagnosed from January 1978 to December 2019. Follow-up started at kidney disease presentation and ended at death or August 2020. Clinical presentation, survival and prognostic factors were analysed. Results: From 123 patients with amyloid nephropathy, 111 had definite amyloid typing and were analysed. AA amyloidosis, the most frequent type (56.1%), related mainly to chronic infection (47.8%) and chronic inflammatory arthritis (29.0%). AL amyloidosis was present in 25.2% of patients and hereditary forms in 6.5% (4.1% AFibE526V, 2.4% ATTRV30M). During follow-up, 73.9% of AA and 54.8% of AL patients progressed to end-stage renal disease, and 79.7% of AA and 77.4% of AL died; median global survival was 66.0 (95%CI, 33.0-99.0) and 18.0 (95%CI, 9.3-26.7) months (p=0.025), respectively. There were no significant differences in renal outcome and survival on dialysis between these two types. In multivariate analysis, cardiac involvement at presentation (HR 5.59 [95%CI, 2.73-11.44]) and eGFR<30mL/min/1.73m2 (HR 2.13 [95%CI, 1.13-4.00]) independently influenced AA and AL amyloidosis survival. In AL, cardiac involvement at presentation was an independent predictor of death (HR 6.63 [95%CI, 2.04-21.56]) and early mortality. Conclusions: AA amyloidosis and related chronic infections are still relevant among Portuguese patients. Advanced disease at presentation explains the poor outcomes in AL amyloidosis. Earlier recognition, accurate fibril subtyping and timely therapy institution are essential to halt disease progression and improve prognosis.