Renal Manifestations

Progressive glycosphingolipid (particularly GL-3) accumulation may lead to irreversible and potentially life-threatening clinical sequelae in the kidney. Patients with Fabry disease may develop proteinuria which progresses to isosthenuria and alterations of tubular reabsorption, secretion, and excretion.

Urinalysis results

Urinalysis is characterized by proteinuria, hematuria, and lipiduria,1 beginning in childhood. Polarization microscopy of free urine or urinary sediment reveals birefringent lipid globules with characteristic “Maltese crosses”.2

Renal biopsy results

While GL-3 deposits are primarily found in the lysosomes of the vascular endothelium,2 renal biopsy studies of young hemizygotes show diffuse lipid accumulation in all glomerular, vascular, and interstitial cells, and tubular involvement primarily in distal convoluted tubules and loops of Henle.

Glycosphingolipid-enlarged cells

 renal capillary endothelium contains accumlated particles of GL-3

Light microscopy of renal capillary endothelium. Arrows indicate areas of GL-3 accumulation.

With age, intimal thickening and degenerative glomerular and tubular changes are apparent.3

Intimal thickening and degenerative changes

 atrophic and hyalinized glomeruli characteristic of end-stage renal disease in a patient with Fabry disease

Light microscopy shows atrophic and hyalinized glomeruli characteristic of end-stage renal disease in a patient with Fabry disease.

End-stage renal disease

Renal complications generally signal the end stage of Fabry disease, and are the most frequent cause of death among affected patients (hemizygotes). Azotemia usually occurs in patients by the third to the fifth decade of life,2 although renal failure has also been reported in patients as young as 16 years old.4

Autopsy of a patient with end-stage renal disease

 end-stage disease with scarring and cyst formation

Gross appearance of end-stage disease with scarring and cyst formation. External view (left), cut surface (right). Used with permission. {Barness, 2000}

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References:

1. Meroni M, A Sessa, G Battini, S Tazzari, L Torri Tarelli. Kidney involvement in Anderson-Fabry disease. Contrib Nephrol. 1997;122:178-184.

2. Desnick RJ, YA Ioannou, CM Eng. α-galactosidase A deficiency: Fabry disease. In: The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill, 2001: 3733-3774.

3. Gubler MC, G Lenoir, JP Grunfeld, et al. Early renal changes in hemizygous and heterozygous patients with Fabry's disease. Kidney Int. 1978;13:223-235.

4. Sheth KJ, DA Roth, MB Adams. Early renal failure in Fabry's disease. Am J Kidney Dis. 1983;2:651-654.