Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease

Kidney Blood Press Res. 2017;42(1):1-15. doi: 10.1159/000464312. Epub 2017 Feb 28.

Abstract

Background/aims: Fabry disease (FD) is a rare inherited lysosomal storage disease with common and serious kidney complications. Enzyme replacement therapies (ERT) with agalsidase-α and -β were investigated to characterize their therapeutic effect on kidney function in FD patients with Classic phenotype.

Methods: The prospective FD cohort consisted of 98 genetically confirmed patients (females, n = 61, males, n = 37). The median [interquartile range] follow-up time (time difference from first to last visit) was 9 [6, 12] years. The median age of ERT start was 36 [21 - 54] years for females and 39 [28 - 49] years for males.

Results: A disease progression model was developed to (i) characterize the time course of estimated glomerular filtration rate (eGFR) and (ii) evaluate therapeutic effects of ERT on kidney function. Change in eGFR over time was best described by the linear model. Females had stable kidney function with and without ERT (eGFR slopes of -0.07 ml/min/1.73m^2 per year and 0.52 ml/min/1.73m^2 per year, respectively). Males with ERT showed an eGFR decrease of -3.07 ml/min/1.73m^2 per year.

Conclusion: Mathematical disease progression modeling indicates that there is no clear therapeutic effect of ERT on kidney function in adult patients with Classic Phenotype of FD. Interpretation of these findings should take into account that the study is not randomized and lacks a placebo controlled group. Further investigations are warranted to clarify whether earlier ERT initiation before 18 years of age, higher ERT dose or more intensive therapies can preserve kidney function.

Keywords: Classic phenotype; Enzyme replacement therapy; Fabry disease; Modeling; Nephropathy.

MeSH terms

  • Adult
  • Disease Progression
  • Enzyme Replacement Therapy / methods*
  • Fabry Disease / drug therapy*
  • Fabry Disease / pathology
  • Fabry Disease / physiopathology
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Isoenzymes / therapeutic use
  • Kidney / drug effects
  • Male
  • Middle Aged
  • Models, Theoretical*
  • Young Adult
  • alpha-Galactosidase / therapeutic use

Substances

  • Isoenzymes
  • alpha-Galactosidase
  • agalsidase beta