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 and Blood Pressure Research

Siegenthaler M.³  Nowak A.³  Pfister M.²  Huynh-Do U.⁴  Marti H.-P.¹  Koch G.² 

[1] Department of Medicine, Haukeland University Hospital, Department of Clinical Medicine, University of Bergen, Bergen, Norway$$;Department of Pediatric Clinical Pharmacology, Pediatric Pharmacology and Pharmacometrics Research Center, University of Basel Children’s Hospital (UKBB), Basel, Switzerland$$;Department of Internal Medicine, University Hospital Zurich and University of Zurich, Zurich, Switzerland$$;Department of Nephrology, Hypertension and Clinical Pharmacology, Department of Clinical Research, Inselspital, University of Bern, Bern, Switzerland$$

关键词: Enzyme replacement therapy;    Fabry disease;    Classic phenotype;    Modeling;    Nephropathy;   

DOI  :  10.1159/000464312

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

Unknown