Prognostication of survival and progression to dialysis in AA amyloidosis

INTRODUCTION: In the last decade, the availability of accurate diagnostic techniques, the recognition of the importance of achieving low SAA concentrations, and the accessibility of novel effective treatments for the underlying disease has greatly impacted the management of AA amyloidosis. This thesis reports the outcome of 200 consecutive patients diagnosed between 1991 and 2015. MATERIAL & METHODS: Patients were evaluated every 6 months. Treatment was targeted at reduction (if possible normalization) of SAA (available from baseline in 97% of patients). The cutoffs used to dichotomize continuous variables were determined by ROC analyses based on death or dialysis at 4 years. RESULTS: Median age was 58 years (range 20-83 years) and 40% of patients were males. The underlying disease was arthritis in 31% (rheumatoid arthritis in 20%), inflammatory bowel disease in 13%, infections in 10%, hereditary periodic fever in 8%, Castleman disease in 4%, and other inflammatory diseases in 2%. In 32% of cases the underlying disease remained unknown. Interestingly, 39% of patients in this latter group were obese, suggesting that obesity-related inflammation might be the cause of AA amyloidosis in a subgroup of patients. The median duration of inflammatory disease before the diagnosis of amyloidosis was 13.7 years. In 5% of patients the identification of the underlying disease followed the diagnosis of amyloidosis. The kidney was involved in 100% of subjects, the heart in 14%, the liver in 8%, and the gastrointestinal tract in 6%. Excluding 10% of patients who were on dialysis at the time of diagnosis, median (range) proteinuria was 3.3 g/24h (0.5-45 g/24h) and eGFR 35 mL/min (4-138 mL/min). With a median follow-up of living patients of 4.4 years, median survival and time to dialysis were 11.9 and 11.2 years, respectively. The variables independently predicting survival were age >55 years (median 6.8 vs. not reached, P<0.001), underlying infection (median 8.9 vs. 11.9 years, P=0.021), and eGFR <45 mL/min (77% vs. 93% at 5 years, P=0.028). Renal survival was independently predicted by proteinuria >4 g/24h (median 6.7 vs. 16.5 years, P=0.004), and eGFR <35 mL/min (median 5.9 vs. 14.3 years, P<0.001). Two staging systems were generated . Baseline SAA did not predict the outcome; however, the ability to reach a low SAA concentration (<10 mg/L) at 6 months independently improved renal survival (median 5.3 vs. 13.7 years, P=0.010). No deaths were observed in the 17 patients treated with biologic agents frontline, but statistical significance was not reached due to low numbers (P=0.059). DISCUSSION & CONCLUSIONS: Early diagnosis, at a stage when renal function is not irreparably compromised, and effective therapy are the keys to improve the outcome of patients with AA amyloidosis.