Journal of Inherited Metabolic Disease

, Volume 31, Issue 4, pp 508–517 | Cite as

Abnormal expression and processing of uromodulin in Fabry disease reflects tubular cell storage alteration and is reversible by enzyme replacement therapy

  • P. Vylet’al
  • H. Hůlková
  • M. Živná
  • L. Berná
  • P. Novák
  • M. Elleder
  • S. Kmoch
Open Access
Original Article


Uromodulin (UMOD) malfunction has been found in a range of autosomal dominant tubulointerstitial nephropathies associated with hyperuricaemia, gouty arthritis, medullary cysts and renal failure—labelled as familial juvenile hyperuricaemic nephropathy, medullary cystic disease type 2 and glomerulocystic kidney disease. To gain knowledge of the spectrum of UMOD changes in various genetic diseases with renal involvement we examined urinary UMOD excretion and found significant quantitative and qualitative changes in 15 male patients at various clinical stages of Fabry disease. In untreated patients, the changes ranged from normal to a marked decrease, or even absence of urinary UMOD. This was accompanied frequently by the presence of aberrantly processed UMOD lacking the C-terminal part following the K432 residue. The abnormal patterns normalized in all patients on enzyme replacement therapy and in some patients on substrate reduction therapy. Immunohistochemical analysis of the affected kidney revealed abnormal UMOD localization in the thick ascending limb of Henle’s loop and the distal convoluted tubule, with UMOD expression inversely proportional to the degree of storage. Our observations warrant evaluation of tubular functions in Fabry disease and suggest UMOD as a potential biochemical marker of therapeutic response of the kidney to therapy. Extended comparative studies of UMOD expression in kidney specimens obtained during individual types of therapies are therefore of great interest.


Enzyme Replacement Therapy Fabry Disease Nephrogenic Diabetes Insipidus Distal Convolute Tubule Outer Medulla 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • P. Vylet’al
    • 1
  • H. Hůlková
    • 2
  • M. Živná
    • 1
  • L. Berná
    • 2
  • P. Novák
    • 3
  • M. Elleder
    • 1
  • S. Kmoch
    • 1
    • 4
  1. 1.Center for Applied Genomics and Institute for Inherited Metabolic DisordersCharles University 1st Faculty of MedicinePragueCzech Republic
  2. 2.Institute for Inherited Metabolic DisordersCharles University 1st Faculty of MedicinePragueCzech Republic
  3. 3.Laboratory of Molecular Structure Characterization, Institute of MicrobiologyAcademy of Sciences of the Czech RepublicPragueCzech Republic
  4. 4.Center for Applied Genomics and Institute for Inherited Metabolic DisordersPrague 2Czech Republic

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