The Role Of Relevant Molecules In Childhood Minimal Change Nephrotic Syndrome

Primary nephrotic syndrome is a common disease during childhood, large percentage of which is minimal change neplirotic syndrome, about 80 percentages. Although most of the patients were sensitive to steroid treatment, some patients were prone to frequent-relapse; further more, some additional patients were resistant to steroid treatment. Long-term steroid treatment resulted in a series of side-effect, consequently influenced children's health. Moreover, they would likely to develop into renal insufficency ultimately. Therefore, studies about pathogenesis of proteinuria, mechanism of frequent-relapse and resistant to steroid in primary nephrotic syndrome (especially in MCNS) are the focus, to which pediatric nephrologists should pay more attention, all the times.Heavy proteinuria, a main characteristic of naphrotic syndrome, is caused by increasing permeability of glomerular filtrated barrier to plasma albumin. The glomerular filtrated barrier is composed of three layers: a fenestrated endothelium, glomerular basement membrane (GBM), and epithelial cell (podocyte) layer with distal foot processes and interposed slit diaphragms (SD). Only recently, increased insight in the molecular makeup of the podocyte foot processes and slit diaphragm led to the support for the pivotal role of these structures in the maintenance of permselectivity. Under electron microscope, foot processes extensive effacement was the diagnostic character of minimal change nephrotic syndrome.In order to find out correlated factors in the pathogenesis of minimal change nephrotic syndrome, we used podocyte as a clue, based on prophase study about the renal genes expression of MCNS, examined the expression of nephrin, podocin, FGF-2 and AngptB in minimal change nephrotic syndrome. From different point of view, such as SD-associated molecules, podocyte damage and so on, we discussed the role of them in the mechanisms leading to proteinuria, resistant to steroid and frequent-relapse respectively.Part I The expression of nephrin and podocin mRNA in childhood minimal change nephrotic syndromeObjective Nephrin is a cell-adhesion protein that is defective in congenital nephrotic syndrome of the Finnish type (CNF). Podocin is an integral membrane prorein, involved in autosomal recessive steroid-resistant nephrotic syndrome. Both of them were located in the slit diaphragm. In order to elucidate the role of nephrin and podocin in mechanism of proteinuria, we examined both of their mRNA expression and mean foot process width among children with minimal change nephrotic syndrome.Methods Twenty-four patients with primary nephrotic syndrome were studied, including 17 cases of minimal change nephrolic syndrome and 7 cases of non-MCNS (including mesangial proliferative glomerulonephritis, membranous nephropathy, membranoproliferative glomerulonephritis and focal segmental proliferative glomerulonephritis) diagnosed pathologically. All of them were divided into two groups: steroid-sensitive (SS) group and steroid-resistant (SR) group. In the SS group, two subgroups were setup, frequent relapse; group and infrequent relapse group. Under electron microscope, there was different degree of foot processes effacement in each of them, 18 cases with extensive effacment, while 6 cases with partial effacment. Part of the children was biopsied due to poor response to steroid treatment or relapse during their treatment. Both treated and untreated patients were included in the present study. Control kidney specimens were obtained from nine patients with microscopical hematuria whose electron microscope shown no abnormity in glomerulus and no foot proceses effacement, among them five patients revealed thinner GBM. Real-time fluorescence PCR was used to determine the mRNA levels of nephrin and podocin. We measured the foot process width (FPW) of 8 cases of MCNS and 4 of cases thin basement membrane nephropathy, to evaluate the degree of podocyte damage. The obtained molecular data were related to electron microscopic ultrastructural changes, in particular foot proc...