ATTR V30M Nephropathy: Implications of switching anti-amyloid agents PC134 (#396)

Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.
Joana Tavares, Department of Nephrology, Centro Hospitalar Universitário de Santo António, Porto, Portugal

Main Body of the Abstract
Introduction
Therapy for hereditary transthyretin(ATTRv) amyloidosis changed the history of neuropathy. Concerning ATTRV30M patients with nephropathy, albuminuria is a key feature for outcome. The anti-albuminuric effect of tafamidis was established, but its sustainability after switching therapy was not regarded. Our aim was to review the recurrence of albuminuria after converting tafamidis to other therapies.
Methods
Retrospective cohort study of ATTRV30M patients that started tafamidis from July-2012 to March-2019 and had urinary albumin/creatinine ratio (ACR)≥30mg/g at baseline. End of follow-up: June-2023, liver transplantation, end-stage kidney disease(ESKD) or death; criteria to switch therapy was the progression of neuropathy. Patients participating in clinical trials were not considered.
Results
Six male and 32 female, aged 47(40.5-58.9)years-old, treated with tafamidis had ACR≥30mg/g at baseline; the median eGFR CKD-EPI creatinine and cystatin C was 91.5(71.2-115)ml/min/1.73m2; At the end of follow-up 40% remained on tafamidis, four patients died, two underwent liver transplantation, two evolved to ESKD. 15 switched therapy. Twelve patients started patisiran and three underwent a clinical trial. After the switch to patisiran, albuminuria didn't recur, except in one patient, whose kidney biopsy excluded disease besides amyloidosis; the median eGFR at the time of switch and at end of follow-up was, respectively, 82(68.5-94.3)ml/min/1.73m2 and 80(70.8-93)ml/min/1.73m2; no patient needed renal replacement therapy, neither death was registered.
Conclusions
In this cohort, the tafamidis switch to siRNA therapy showed_ maintenance of the albuminuria remission and stabilization of eGFR._ The findings suggest that the pathogenic derangement caused by glomerular and vascular ATTR-amyloidosis is dynamic and not limited to the deposits.