Trajectories of Kidney Function in Patients with ATTRv Treated with Gene Silencers

Abstract

Hereditary transthyretin amyloidosis (ATTRv; v for "variant") is the most common form of hereditary amyloidosis, with an autosomal dominant inheritance and a variable penetrance. This disease has a significant variability in clinical presentation and multiorgan involvement. While kidney involvement in early-onset ATTRv has been reported in one-third of patients, in late-onset ATTRv it has generally been considered rare. In the present study, we describe trajectories of kidney function over time before and after treatment with gene silencing therapies in a cohort of 17 ATTRv patients with different mutations, coming from Italy (nine subjects treated with inotersen and eight patients treated with patisiran). The analysis of estimated glomerular filtration rate (eGFR) slopes revealed that the average change in eGFR was 0.01 mL/min/1.73 m² per month before initiation and -0.23 mL/min/1.73 m² per month during follow-up for inotersen and -0.62 mL/min/1.73 m² per month before initiation and -0.20 mL/min/1.73 m² per month during follow-up for patisiran. In conclusion, we did not observe any significant difference either between the two groups of treatment or within-group before and after therapy, so gene-silencing therapies may be considered safe for renal function in ATTRv and are not associated with a worsening of eGFR slope.

Keywords: ATTRv; amyloidosis; gene-silencing therapies; kidney involvement.

Figure 1

The graph reports the estimated change in eGFR over time before and after treatment initiation with inotersen (solid blue line) and patisiran (dotted red line), with shades representing 95% confidence intervals. The vertical dotted line represents treatment initiation. No significant difference either between the two groups of treatment or within-group before and after therapy (all p-values > 0.05) was observed.