Glomerular structural factors in progression of congenital nephrotic syndrome

Abstract

The glomerular structural factors associated with progression of congenital nephrotic syndrome of Finnish type (CNF) are incompletely understood. We studied glomerular volume and the proportion of various glomerular subtypes in seven CNF patients (aged 4 months to 3 years). Glomerular tubular connections (GTC) were analyzed in two patients early and late in the disease spectrum (creatinine 0.2 and 2.8 mg/dl, respectively). The proportions of "normal" glomeruli decreased (r=-0.91, P=0.003) and microcystic glomeruli increased (r=0.85, P=0.015), while the fetal and sclerosed glomeruli remained stable (r=0.073 and 0.08 respectively, P=NS for both) with age. The "normal" glomeruli were larger in CNF than in six age-matched minimal change nephrotic patients (P=0.009). GTC analyses in the mild disease showed that 75% of the 12 "normal" glomeruli had normal tubules, and 25% were atubular or were attached to atrophic tubules, while 88% of the 12 fetal glomeruli were either atubular or were attached to atrophic tubules. In the advanced disease, 67% of 12 "normal" glomeruli had normal tubules, and 33% were atubular or atrophic, while none of the fetal or microcystic glomeruli had "normal tubules". Thus atubular glomeruli may play an important role in disease progression in CNF, as it is associated with a progressive decrease in hypertrophied "normal" glomeruli and an increase in largely atubular microcystic glomeruli.

Glomerular sclerosis in kidneys with congenital nephrotic syndrome (NPHS1)

“…The most constant glomerular finding was mesangial sclerosis as reported previously. 13,14 Accumulation of extracellular matrix proteins and cells in the mesangium was evident in practically every glomerulus. Immunohistochemistry revealed that the glomerular tuft contained low numbers of inflammatory cells, indicating that the increased cellularity was caused by reactive mesangial cells.…”