Therapeutic effect of TTR siRNA on hereditary transthyretin amyloidosis (ATTRv) nephropathy.

Background: Hereditary transthyretin amyloidosis (ATTRv) is a fatal disease that affects multiple organs. Up to 30% of patients with ATTRv also experience renal complications, including proteinuria and a decline in eGFR. Recently, new treatments for ATTRv, a tetramer stabiliser and transthyretin small interfering RNA (TTR siRNA) therapeutics, have emerged. However, the effectiveness of these new treatments on renal complications in ATTRv remains unknown.

Methods: We retrospectively collected clinical data from ATTRv patients and analysed the relationship between the initial renal complications and age. We also examined whether the new treatments affected the clinical course of renal symptoms, using eGFR changes or longitudinal data on urine protein/albumin creatinine ratio.

Results: A total of 16 patients' data were collected. Regarding their initial renal complications, we found that patients with proteinuria had an earlier age at onset than those with a decline in eGFR. Notably, longitudinal data showed that TTR siRNA therapeutics reduced proteinuria and increased serum protein, while none of the new treatments could demonstrate a significant improvement in the slope of eGFR decline.

Conclusions: We demonstrated that TTR siRNA therapeutics represent potential candidates for ATTRv nephropathy, despite the fact that their use has been limited to neurological symptoms to date.