Amyloid A (AA) amyloidosis arises from chronic systemic inflammation and is an uncommon but serious complication in patients with cystic fibrosis (CF). Although individual case reports have described AA amyloidosis in CF, comprehensive characterization of its clinical features, organ involvement, treatments, and outcomes has been limited. The authors aimed to define these aspects by combining a review of the literature with three additional cases from their center.
The investigators searched PubMed, Scopus, and Web of Science through November 2025 for published, biopsy‑proven cases of AA amyloidosis occurring in patients with CF. Reported cases were extracted and summarized; the authors added three cases from their own institution to the pooled dataset. Available clinical variables, treatment details, and outcome data were collated for analysis.
A total of 70 patients were included in the pooled analysis, which comprised previously reported cases plus three new cases contributed by the authors. The median age at initial CF diagnosis was 45 months. By contrast, the median age at diagnosis of AA amyloidosis was 21 years, indicating that this complication tended to present in adolescence or early adulthood among the reviewed cases.
Renal disease was the dominant clinical manifestation in this cohort. Of 70 patients, 69 (98.6%) had renal involvement. Nephrotic‑range proteinuria was common, occurring in 74% of patients. The review emphasizes that the kidneys were the principal organ system affected in CF‑associated AA amyloidosis across reported cases.
Treatment details were available for 24 patients. The most frequently reported interventions included renin‑angiotensin‑aldosterone system (RAAS) blockade (reported in 11 patients) and colchicine (9 patients). Corticosteroids were used in five patients. Notably, three patients received biologic therapies targeting proinflammatory cytokines (anti‑IL‑1 or anti‑IL‑6). The authors report that these are the first documented uses of biologic therapies in CF‑associated AA amyloidosis; however, no meaningful clinical response was observed in those cases. The review does not provide standardized protocols, dosing details, or robust comparative data on efficacy.
Outcome data were reported for 55 patients. Of these, 50 patients (91%) died after diagnosis of AA amyloidosis. The median survival following AA amyloidosis diagnosis was 13 months. These findings indicate markedly poor prognosis among reported cases and underscore high mortality associated with this complication in CF.
Given the predominance of renal involvement and the high frequency of nephrotic‑range proteinuria, the authors recommend routine assessment of urinary protein in patients with CF as a strategy that may enable earlier detection of AA amyloidosis. Early identification could allow initiation of supportive measures and consideration of anti‑inflammatory or disease‑modifying approaches, though evidence for specific effective therapies remains lacking.
The limited and heterogeneous treatment data in the literature mean that no treatment standard can be recommended based on this review. The report highlights that biologic agents targeting IL‑1 or IL‑6 were used in three patients without meaningful benefit, indicating that further investigation of targeted anti‑inflammatory strategies is necessary before they can be recommended for this indication.
The review aggregates published case reports and series, which introduces selection and reporting biases. Many clinical details, standardized outcome measures, and long‑term follow‑up data were incomplete or unavailable in the source literature. Treatment regimens were heterogeneous and infrequently reported in depth, preventing firm conclusions about efficacy. The authors call for prospective studies and registries to better define incidence, risk factors, optimal screening strategies, and effective disease‑modifying treatments for AA amyloidosis in CF.
CF‑associated AA amyloidosis is a rare but devastating complication characterized by predominant renal involvement, frequent nephrotic‑range proteinuria, and poor survival. In this pooled analysis of 70 patients, mortality among those with outcome data was 91% with a median survival of 13 months after diagnosis. Routine urinary protein monitoring in patients with CF may permit earlier diagnosis; however, evidence for effective therapies is currently limited and further research is needed to identify and validate disease‑modifying interventions.