Fabry Disease – Renal Impact

Progressive glycosphingolipid (particularly GL-3) accumulation may lead to irreversible and potentially life-threatening clinical sequelae in the kidney. Renal complications generally herald the end stage of the disease and are the most frequent cause of death among classically affected Fabry patients (hemizygotes).

While GL-3 deposits are primarily found in the lysosomes of the vascular endothelium,^[1] renal biopsy studies of young hemizygotes show diffuse lipid accumulation in the glomerular, vascular, and interstitial cells, and tubular involvement primarily in distal convoluted tubules and loops of Henle.^[2]

With age, intimal thickening and degenerative glomerular and tubular changes are apparent.^[2]

Most patients with classical Fabry disease develop proteinuria in late adolescence, which progresses to isosthenuria and alterations of tubular reabsorption, secretion, and excretion.^[1] Azotemia usually occurs by the third to fifth decade of life,^[1] although renal failure has also been reported in patients as young as 16 years old.^[3] Renal complications tend to be less evident in female carriers than in hemizygotes.^[4]

Urinalysis is also characterized by hematuria and lipiduria,^[5] often beginning in childhood. Polarization microscopy of free urine or urinary sediment reveals birefringent lipid globules with characteristic "Maltese crosses^[1] (see also Molcular basis, picture 3)."

References

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

2.Gubler M-C, Lenoir G, Grünfeld J-P, Ulmann A, Droz D, Habib R. Early renal changes in hemizygous and heterozygous patients with Fabry's disease. Kidney Int. 1978;13:223-235.

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

4.Sessa A, Meroni M, Battini G, et al. Renal pathological changes in Fabry disease. J Inher Metab Dis. 2001;24 Suppl 2:66-70.

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