#5209 ALGALSIDASE-BETA STABILIZES RENAL AND CARDIAC INVOLVEMENT: A FOLLOW-UP STUDY OF A BRAZILIAN FABRY DISEASE FAMILY

Abstract

Abstract Background and Aims Fabry Disease (FD) is a multisystemic disorder that affects the function of major organs, such as the kidneys, the heart and the central nervous system, reducing the quality of life and leading ultimately to premature death. Early diagnosis and timely treatment are the cornerstones to change the natural history of this disorder. Method To evaluate clinical, laboratory and renal histological profiles of FD patients with a classic pathogenic variant (p.G35V), identified by targeted screening in hemodialysis patients followed by family screening, who were under enzyme replacement therapy (ERT), algalsidase-beta (0.1 mg/kg/e.o.w), for at least 48 months. Kidney biopsy was performed at baseline. Glomerular filtration rate, estimated according to the CKD-Epi equation, 24h-urinary protein and albumin were measured annually. Cardiac manifestations were evaluated by eletrocardiogram, transthoracic echocardiography (TTE) or magnetic resonance imaging (cMRI) at baseline and at the end of the study. cMRI was not performed in the index patient, due to CKD 5D, and in a pregnant female patient. Results Nine patients (age: 33.8±12.3 years) were followed-up for 80.67±5.43 months. Their main clinical manifestations were hypohidrosis (67%) gastrointestinal symptoms (56%), cornea verticilata and acroparesthesia (100%). Angiokeratomas were present only in males (100%). Five (56%) and 3 (33%) patients presented CKD G1 and G2, respectively. Only the index case presented CKD G5D. Short PR interval was observed in 44.4%. LVH was detected by TTE in 2 patients (index case and a 46-years old female); whereas based on cMRI no patient had LVH and one female had myocardial fibrosis. Patients received ERT for 70.22±12.92 months, together with adequate adjunctive therapy. eGFR and proteinuria / albuminuria remained stable during the follow-up in both sexes. Female patients presented a mean reduction of LV mass index of 9.73g/m2 (CI95%: -26.9 - 6.8). Patients who started ERT older than 30 years tended to have a higher interventricular septal thickness at the end of the follow-up (8.4 ± 2.2 vs 10.0 ± 2.7 mm; P = .08). Concerning the kidney biopsy findings, patients with higher proteinuria presented more global glomeruli sclerosis; and mild interstitial fibrosis (5%) could be detected even among young patients with normal albuminuria and eGFR. There was a significant correlation between baseline global glomeruli sclerosis and albuminuria at baseline (r=0.9; P = .01) and at the end of the follow-up (r=0.87; P = .01); and between baseline interstitial fibrosis and proteinuria at the end of the follow-up (r=0.80; P = .03). Conclusion Females with a pathogenic variant (p.G35V) for FD may develop cardiac and renal injury. FD-related renal histological changes and chronic tissue damage may be present before clinical and laboratory signs of renal dysfunction. Persistence of proteinuria during ERT might be related to the presence of interstitial fibrosis. Treatment with ERT may stabilize renal and cardiac involvement in FD. Regular monitoring and adequate pathogenetic and adjunctive treatment should be offered to FD patients of both sexes. Kidney biopsy is an important tool to evaluate pre-clinical renal involvement. Timely treatment may potentially change the natural history of the disease.