Glomerular involution in children with frequently relapsing minimal change nephrotic syndrome: An unrecognized form of glomerulosclerosis?

Abstract

Global glomerulosclerosis can be divided in the vascular (obsolescent) type and the glomerulopathic (solidified) type. In biopsies from children with recurrent nephrotic syndrome owing to minimal change nephropathy (MCN), we noticed small, globally sclerosed glomeruli that appeared to be distinct from global glomerulosclerosis. These small sclerosed glomeruli are best described as involuted glomeruli. We have characterized these involuted glomeruli in detail. We studied biopsies of 18 children (11 male, 7 female) with frequently relapsing MCN and evaluated possible explanatory variables. The involuted glomeruli can be differentiated from the other types of global glomerulosclerosis. Most notable is the presence of vital podocytes and parietal epithelial cells, which have retained their staining characteristics, in between the matrix, and the absence of periglomerular and tubulo-interstitial fibrosis. We observed involuted glomeruli in 12 out of 18 biopsies; the median percentage of involuted glomeruli was 6% (range 0-33%). The percentage of involuted glomeruli correlated with age at renal biopsy and the interval between onset of disease and time of renal biopsy, but not with gender, age at onset of disease, or prednisone dose. Multivariate analysis revealed that the interval between onset of disease and time of renal biopsy was the only independent predictor. In conclusion, glomerular involution is a special form of global glomerulosclerosis. The absence of periglomerular and tubulo-interstitial fibrosis suggests a different pathogenesis. Glomerular involution is a slow process. The clinical data suggest that involution is related to the duration of the disease process.

Dimethylarginines as Risk Markers of Atherosclerosis and Chronic Kidney Disease in Children with Nephrotic Syndrome

“…In NS there is an uncontrolled increase in the concentration of lipoproteins in these cells, which results in their proliferation [15,17]. In addition, lipoprotein complexes remain in glomerular capillaries [18]. In the mesangium, lipoproteins are oxidized (oxLDL) and in this form they stimulate the production of antibodies against themselves.…”

The not-so-minimal lesions of the idiopathic nephrotic syndrome of childhood

“…Small sclerotic glomeruli have been previously reported in children with congenital nephrotic syndrome, 8 but because they were not characterized with immunohistochemical markers, their precise phenotype and pathogenesis remain unknown. Interestingly, in the study of Dijkman et al, 6 the presence of microglomeruli was not predictive of outcome.…”

“…The not-so-minimal lesions of the idiopathic nephrotic syndrome of childhood Into this histological conundrum falls the study of Dijkman et al, 6 who, in a recent issue of Kidney International, reported the presence of a unique glomerulosclerotic lesion in two-thirds of a group of children with steroid-dependent or frequently relapsing INS (Figure 1). Using immunohistochemical markers for glomerular cell constituents and extracellular matrix proteins, the authors elegantly characterized this lesion as a form of glomerular involution, distinguishing it from the classic glomerulopathic and vascular types of glomerulosclerosis.…”

“…12 Subsequent studies have consistently demonstrated a more severe form of histology underlying childhood INS. Th e clinical significance of the glomerular lesions described by Dijkman et al 6 and by other researchers in these patients would be best addressed by a prospective multicenter study sufficiently powered to evaluate contemporary risk factors and clinically appropriate end points -in other words, an ISKDC for the new millennium.…”

Vasopressin: A look at dialysis hypertension and autonomic dysfunction

“…12 Subsequent studies have consistently demonstrated a more severe form of histology underlying childhood INS. Th e clinical significance of the glomerular lesions described by Dijkman et al 6 and by other researchers in these patients would be best addressed by a prospective multicenter study sufficiently powered to evaluate contemporary risk factors and clinically appropriate end points -in other words, an ISKDC for the new millennium.…”