Glomerular expression of nephrin is decreased in acquired human nephrotic syndrome

Background. Nephrin recently has been identified as a putative adhesion mol ecule, expressed in the glomerulus, in which mutations cause congenital nep hrotic syndrome of Finnish type. We sought to determine whether expression of nephrin is altered in human glomeruli in patients with acquired nephroti c syndrome. Methods. We performed PCR amplification of nephrin cDNA, using cDNA previou sly prepared from single human glomeruli plucked fresh from the surface of human renal biopsies. We had available four cases of nephrotic syndrome (on e membranous, three minimal change) and six normal controls. PCR product qu antitation was by gel densitometry, confirmed by enzyme-linked immunosorben t assay using a specific oligonucleotide probe. Results were corrected for reaction efficiency and glomerular cellularity by expression as a ratio to levels of the 'housekeeping gene' glyceraldehyde phosphate dehydrogenase. Results. Glomerular levels of nephrin mRNA are significantly decreased in c ases of minimal change nephrotic syndrome. An apparent reduction was also s een in the single case of membranous nephropathy which was available for st udy. Conclusions. Abnormalities of nephrin expression appear to be associated wi th acquired as well as congenital causes of human nephrotic syndrome.