title: Urinary protein excretion pattern and renal expression of megalin and cubilin in nephropathic cystinosis.
abstract: BACKGROUND
  Nephropathic cystinosis is the most common cause of inherited renal Fanconi syndrome, caused by mutations in lysosomal cystine carrier cystinosin that result in lysosomal cystine accumulation throughout the body. How defects in cystinosin cause proximal tubular dysfunction is not known. We hypothesized that cystine accumulation could cause disturbed proximal tubular endocytosis by megalin and cubilin.
  
  
  METHODS
  Megalin, cubilin, and their ligands were studied in kidney tissue by means of immunohistochemistry. Urinary protein excretion pattern was evaluated.
  
  
  METHODS
  Kidney tissue from a patient with cystinosis was compared with minimal change nephrotic syndrome tissue, end-stage renal disease tissue, and control renal tissue. Urine from 7 patients with cystinosis was compared with 6 control samples.
  
  
  RESULTS
  Expression of megalin, cubilin, and ligands (transferrin, albumin, vitamin D-binding protein, alpha(1)-microglobulin, retinol-binding protein, and beta(2)-microglobulin) in convoluted proximal tubules of cystinotic kidney was similar to that in other kidney specimens. In straight tubules, low-molecular-weight proteins were present in only cystinotic kidney samples. Next to low-molecular-weight proteins and albumin, urinary excretion of immunoglobulin G was increased in patients with cystinosis with Fanconi syndrome compared with controls. This was already observed at an early age, suggesting enhanced glomerular permeability in patients with cystinosis.
  
  
  CONCLUSIONS
  This study is essentially observational, and immunohistochemical data are based on 1 cystinotic kidney.
  
  
  CONCLUSIONS
  Our findings indicate that low-molecular-weight proteinuria in patients with cystinosis is not caused by decreased megalin and cubilin expression, and glomerular damage might already be present at early stages of the disease.
authors.affiliation: Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.wilmer@cukz.umcn.nl
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Wilmer
authors.forename: Erik I
authors.initials: EI
authors.lastname: Christensen
authors.forename: Lambertus P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: Leo A
authors.initials: LA
authors.lastname: Monnens
authors.forename: Elena N
authors.initials: EN
authors.lastname: Levtchenko
mesh_terms: D000293:Adolescent; D002648:Child; D003554:Cystinosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000096:biosynthesis*; D008297:Male; D011507:Proteinuria / Q000652:urine*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor