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

Summary

The investigators will perform a study with two major components. The first is a natural history study of untreated Fabry patients. This study component will detail kidney microscopic structural changes in Fabry patients before starting enzyme replacement therapy and will correlate these changes with kidney function, including glomerular filtration rate and urinary albumin excretion rate. The investigators will perform studies on samples obtained at baseline, or before enzyme replacement therapy is initiated. The goal of our study is to find kidney microscopic changes in the biopsies that are associated with kidney disfunction. Our hypotheses for this study are:

1. Much of the natural history of Fabry renal structural changes will occur without detectable renal functional alterations.
2. Structural changes associated with the initial onset of proteinuria and those associated with the subsequent progressive loss of filtration function will differ and will be best described by non-linear models.
3. There will be sufficient precision of Fabry renal structural-functional relationships to support renal structure as an acceptable clinical trial surrogate endpoint for later renal functional deterioration.

The second component examines the effects of age and gender at start of enzyme replacement therapy (ERT), as well as dosage levels of ERT on the renal cellular clearance of GL3 from Fabry patients by comparing baseline to follow-up kidney biopsies performed 5, 11, and 60 months later, with all comparisons matched for ERT treatment duration. Our hypotheses for this component of the study are as follows:

1. Enzyme Replacement Therapy(ERT) instituted at younger ages is more effective in reducing podocytes(PC),distal tubular cells(DTC),and arterial smooth muscle cells (ASMC)GL-3 than in older Fabry patients.
2. Earlier institution of ERT will stabilize PC numbers while later ERT institution, especially in proteinuric adults, may not prevent progressive decline in PC numbers and associated glomerular sclerosis, tubulointerstitial injury, and GFR loss.
3. Whereas lower ERT dose may effectively clear GL-3 from endothelial and mesangial cells, it will be less effective in clearing GL-3 from PC and also from DTC and ASMC.
4. Affected cells will be cleared of GL-3 equivalently in females and males.

Conditions

• Fabry Disease

Sponsors & Collaborators

• Rare Diseases Clinical Research Network

  collaborator NETWORK

• National Center for Advancing Translational Sciences (NCATS)

  collaborator NIH

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• Washington University School of Medicine

  collaborator OTHER

• Haukeland University Hospital

  collaborator OTHER

• University of Minnesota

  lead OTHER

Principal Investigators

• Chet Whitley, MD · University of Minnesota

• Michael Mauer, MD · University of Minnesota

Eligibility

Min Age

1 Year

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-10-31

Primary Completion

2030-07-31

Completion

2030-07-31

Countries

• United States

Study Locations