PODOCYTES, PROTEINURIA AND TREATMENT IN FABRY NEPHROPATHY

E. ZOTTA; LAGO N,; ABRIL SEYAHIAN,; SCHIEL A; CANZONIERI R; TRIMARCHI H; OCHOA F; MURYAN A; C. COSTALES-COLLAGUAZO,

Congreso; IMBS; 2018

Fabry is X-linked recessive disease due to lysosomal alpha-galactosidase deficiency. This defect is manifested in the difficulty to metabolize a fatty substance, globotriosylceramide (Gb3) in the lysosomes, producing the generalized accumulation of this metabolite, reason for the systemic affection of different organs. Nephropathy is associated with lysosomal inclusions at the level of podocytes and tubular cells. The renal manifestations such as proteinuria by the alteration in the filtration barrier is appear. So far, no tubular involvement has been described as a cause of urinary protein loss. Fabry disease currently has no cure, but an enzyme replacement treatment has been achieved thus preventing the continuous accumulation of Gb3. The marker to include the patients in this treatment is presence of microalbuminuria We have two objectives in our work. One is related to study the development of proteinuria and the second to obtain an early biomarker of renal alteration to include the patients in replacement therapy before damage, in search of a better survival1. Megalin is an endocytic receptor type LDLR, at apical membrane of the proximal tubule, with multiple protein ligands such as albumin. Immunohistochemistry techniques were performed on 11 samples (CEPEA, Department of Pathology, UBA). Biopsies in paraffin (3) and electron microscopy (8), previously dewaxed or exposed to saturated sodium hydroxide solution respectively, for further processing for fluorescence and peroxidase-DAB immunostaining to detect megalin. Considering that the normal expression pattern is at the apical border, our results suggest an alteration in protein endocytosis due to lack of recycling of megalin that would indicate a mixed origin of proteinuria.2. In Fabry nephropathy, a dual problem coexists: the reluctance of many nephrologists to start enzyme replacement until signs or symptoms of renal disease appear and the lack of biomarkers of early renal damage. 44 Fabry patients (British Hospital Buenos Aires) were studied. A mid-stream freshly voided urine sample was collected on-site after a minimum of 3 hours without voiding. Renal biochemical parameters were determined Smears were performed and they were studied by immunofluorescence using rabbit anti-synaptopodin antibody. Podocytes were counted in 10 randomly chosen x20 fields and the average was considered as the final count for each subject. The results were corrected based on the levels of urinary creatinine found in each sample and compare with the presence of microalbuminuria. Control patients recruited among potential kidney donors-We demonstrate the presence of increased podocyturia in Fabry disease suggesting that the detachment of damaged podocytes may precede proteinuria. The presence of urinary podocytes could open a new chapter in the clinical approach of glomerulopathies and establish an earlier path or specific progression than proteinuria.