Urinary Protein Excretion Pattern and Renal Expression of Megalin and Cubilin in Nephropathic Cystinosis
Received 30 August 2007; accepted 3 March 2008. published online 06 May 2008.
Refers to article:
The Renal Fanconi Syndromes: The Proper Study of Mankind is Man
Anthony G. Norden
American Journal of Kidney Diseases
June 2008 (Vol. 51, Issue 6, Pages 875-876) Full Text |
Full-Text PDF (69 KB)
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.
Study Design
Megalin, cubilin, and their ligands were studied in kidney tissue by means of immunohistochemistry. Urinary protein excretion pattern was evaluated.
Setting & Participants
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, α1-microglobulin, retinol-binding protein, and β2-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.
Limitations
This study is essentially observational, and immunohistochemical data are based on 1 cystinotic kidney.
Conclusion
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.
1Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
2Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark
3Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands
4Department of Pediatrics, University Hospital Leuven, Leuven, Belgium.
Address correspondence to Martijn J. Wilmer, Laboratory of Pediatrics and Neurology (656), Radboud University Nijmegen Medical Centre, PO 9101, 6500 HB Nijmegen, The Netherlands.
ABSTRACT