Noncollagenous matrix components of glomeruli in congenital nephrotic syndrome of the Finnish type: evidence of abnormal splitting of nidogen?

The congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal recessive disease with proteinuria starting already in utero, prematurity and nephrotic syndrome developing within the first weeks of life. The basic defect of this disease is unknown but has been suggested to be restricted to the kidney glomeruli and especially to the glomerular basement membrane (GBM). The location of the major matrix components in the glomeruli of CNF patient kidneys has previously been reported. Using indirect immunofluorescence microscopy we here describe the more recently characterized components of the glomerular extracellular matrix, including nidogen, tenascin, vitronectin and chondroitin sulfate proteoglycan in CNF and control kidney glomeruli. The accumulation of tenascin and chondroitin sulfate in the renal interstitium as well as a more granular deposition pattern of vitronectin in the mesangium of CNF glomeruli as compared to the control kidneys were observed. These changes were considered secondary to the massive proteinuria, reflected also by the presence of glomerular sclerosis and interstitial fibrosis in the CNF kidney samples. Additionally, analysis of GBM components by immunoblotting revealed either increased or decreased proportionate amounts of fibronectin and laminin in the GBM of CNF kidneys, respectively. Interestingly, different proportionate amounts of proteolytic fragments of nidogen were found in CNF glomeruli as compared to controls. Equal levels of nidogen mRNA were found in the cortical tissue of CNF and control glomeruli. Since nidogen is crucial for the supramolecular organization of basement membranes, these results suggest that an unusual fragmentation of nidogen, due to abnormal assembly, degradation or reorganization of glomerular extracellular matrix, may be associated with the basic defect of CNF.