We determined the proportion of adults with late-onset Pompe disease (LOPD) with clinically important changes in 6-minute walk distance (6MWD) and/or forced vital capacity (FVC) after switching from alglucosidase alfa (alg) to cipaglucosidase alfa plus miglustat (cipa+mig) in PROPEL (NCT03729362). This post hoc analysis (95 patients) used published anchor- and distribution-based minimal clinically important differences for 6MWD (in meters for anchor-based; % predicted for distribution-based) and a 3 % threshold for FVC (% predicted). For 6MWD, a higher percentage of patients improved after switching to cipa+mig versus alg plus placebo (alg+pbo) (anchor-based: 29.2 % versus 13.3 %; distribution-based: 33.8 % versus 13.3 %), fewer patients worsened (anchor-based: 12.3 % versus 26.7 %; distribution-based: 7.7 % versus 13.3 %). For FVC, 27.7 % versus 0.0 % improved for cipa+mig versus alg+pbo, 27.7 % versus 53.3 % worsened. Overall, 50.8 % versus 13.3 % of patients experienced improvements in 6MWD (% predicted) and/or FVC with cipa+mig versus alg+pbo, 30.8 % versus 56.7 % worsened. For combined responses from 6MWD (% predicted) and FVC (% predicted), the odds of a better versus a lower response category (improvement > stability > worsening) were 4.05 (95 % confidence interval 1.73-9.51) times higher for cipa+mig than alg+pbo (P = 0.0013). Adults with LOPD switching from alg to cipa+mig have greater chances of clinically relevant motor and lung function improvements than those remaining on alg.

Renal involvement in Fabry disease is a major determinant of overall disease prognosis and early enzyme replacement therapy seems effective in preventing progression of kidney injury. Gb3 storage, glomerular sclerosis and tubulo-interstitial fibrosis may occur with minimal or no changes on standard renal tests, hence alternative markers of renal dysfunction are crucial. In this study we compared several biomarkers with albuminuria in the identification of incipient Fabry nephropathy and their diagnostic accuracy to identify chronic kidney disease (CKD) stage ≥ 2.In this multicentre, prospective, cross-sectional and diagnostic test study, a cohort of 78 Fabry patients and 25 healthy controls was consecutively recruited. Patients were grouped by severity of nephropathy: 1) albuminuria < 30 mg/g; 2) albuminuria 30–299 mg/g; 3) albuminuria > 300 mg/g; 4) glomerular filtration rate (GFR) < 60 mL/min/1.73 m2. Several index tests, namely biomarkers of glomerular (transferrin and type IV collagen) and tubular (α1-microglobulin, N-acetyl-β-glucosaminidase and alanine aminopeptidase) dysfunction were compared with the reference standard (albuminuria).Significant increase of all tested biomarkers in Fabry patients, even in the subgroup of patients without evidence of nephropathy. We also found inverse significant correlations between estimated GFR and collagen type IV (ρ = − 0.289; p = 0.003) or N-acetyl-β-glucosaminidase (ρ = − 0.448; p < 0.001), which were stronger than with albumin (ρ = − 0.274; p = 0.019). There was also better diagnostic accuracy of N-acetyl-β-glucosaminidase to predict CKD stage ≥ 2.These results suggest that studied biomarkers may overcome the limitations of albuminuria as sensitive marker of early renal dysfunction and as marker for CKD progression risk. These biomarkers may also define novel early stages of nephropathy characterized by mesangial expansion and/or tubular damage.