Natural History and Structural Functional Relationships in Fabry Renal Disease Treatment Outcomes(Changes)in Fabry Renal Disease Study

Fabry disease is a rare genetic disease with deficient activity of enzyme alpha-galactosidase A. Deficient activity of this enzyme leads to the accumulation of lipid-derived inclusions in different organs including kidney, heart and vessels. These inclusions can be found in the kidney even before birth. The earliest known clinical manifestation of Fabry kidney disease is the appearance of excess protein in the urine, which usually occurs in the second decade of life. However, our studies, as well as those of other investigators show evidence that kidney injury starts much earlier. Once excess protein is found in the urine, kidney function deterioration becomes progressive, and most Fabry patients require kidney transplantation or hemodialysis in the third to fifth decade of life. The lesion or composite of lesions responsible for functional deterioration of the kidney in Fabry disease are not well known. Their delineation using quantitative, unbiased, morphometric methods will help to understand this disease, and to develop surrogate structural outcomes for early intervention trials. Enzyme replacement therapy may stabilize kidney function. However, its long-term effect on kidney survival is not known. Moreover, there is no early known predictor of kidney dysfunction to adjust and evaluate effectiveness of enzyme replacement therapy. Our studies of renal GL-3 clearance comparing pre-and post-ERT renal biopsies using the above methods will allow us to determine whether age at institution of treatment and ERT dose affect ERT induced GL-3 cellular clearance, especially from those cells where ERT is less effective, i.e., podocytes, vascular smooth muscle cells and distal tubular cells. Finally, it is our hypothesis that mosaicism in Fabry disease females is such that cells such as podocytes are either affected or normal and that ERT clearance in the affected podocytes in females will, as in males, be dependant on age of institution of treatment and ERT dose.

Inclusion criteria

• Patients diagnosed with Fabry disease who have/have not received enzyme replacement therapy where a clinical decision has been made to obtain a kidney biopsy, a GFR, and urinary albumin studies or where patients have previously completed clinical trials which included measures of renal function and renal biopsies.

Exclusion criteria

• Patients with serum creatinine more than 2.5 mg/dL or known to have a renal disease other than Fabry.