The hypothesis that detachment of podocytes leads to albuminuria was tested by studying the single nephron albuminuria in vivo after injecting a saponin solution (0.6 mg/ml) in Bowman's space of superficial glomeruli, which produces selective damage of the podocytes, in female Munich-Wistar-Frömter rats. Animals were subsequently installed under a fluorescence microscope, a purified fluoresceinated rat albumin solution was intravenously injected and the passage of the fluorescent albumin was followed through the microscope. Of the 47 glomeruli injected with the saponin solution (in 6 animals) 46 became fluorescent within seconds with the fluorescence progressing from Bowman's space into the proximal tubule and then in the rest of the tubule. In superficial non-injected and control-injected glomeruli weak fluorescence could be detected only in the glomerular tuft and the peritubular capillaries. Tubuli injected with the saponin solution remained indistinguishable from non-injected tubuli. Electron microscopic study of the saponin-injected glomeruli confirmed the selective removal of podocytes. Immunogold electron microscopy confirmed that the intact albumin molecule effectively passed the glomerular capillary wall at the site where podocyte detachment had occurred. It is concluded that selective removal of podocytes at the single nephron level leads to albuminuria in vivo, and therefore podocytes play a crucial role in regulating the permeability of the glomerular capillary wall.

Background The Flemish Collaborative Glomerulonephritis Group (FCGG) registry is the first population-based native kidney biopsy registry in Flanders, Belgium. In this first analysis, we report on patient demographics, frequency distribution and incidence rate of biopsied kidney disease in adults in Flanders. Methods From January 2017 until December 2019, a total of 2,054 adult first native kidney biopsies were included. A ‘double diagnostic coding’ strategy was used, in which every biopsy sample received a histopathological and final clinical diagnosis. Frequency distribution and incidence rate of both diagnoses are reported and compared with other European registries. Results The median age at biopsy was 61.1 years (IQR, 46.1-71.7), male patients were more prevalent (62.1%) and biopsy incidence rate was 129.3 per million persons per year. IgA nephropathy was the most frequently diagnosed kidney disease (355 biopsies, 17.3% of total) with a similar frequency as in previously published European registries. The frequency of tubulointerstitial nephritis (220 biopsies, 10.7%) and diabetic kidney disease (154 biopsies, 7.5%) was remarkably higher, which may be attributed to changes in disease incidence as well as biopsy practices. Discordances between histopathological and final clinical diagnoses were noted and indicate areas for improvement in diagnostic coding systems. Conclusions The FCGG registry, with its ‘double diagnostic coding’ strategy, provides useful population-based epidemiological data on a large Western-European population and allows subgroup selection for future research.

The hypothesis that damage to the visceral epithelial cell plays a central role in the pathogenesis of focal and segmental glomerulosclerosis was tested by injecting saponin solutions of increasing concentration (0.1, 0.3, 0.6 and 1.0 mg/ml) in Bowman's space of superficial glomeruli in the Munich-Wistar rat. The microinjections were performed both with and without intermittent clamping of the renal vessels during two minutes. After 8 to 14 days the injected glomeruli were examined by light microscopy. The injected glomeruli were classified as, normal (NL), showing visceral epithelial cell damage (VECD), showing focal and segmental glomerulosclerosis (FSGS) or showing global sclerosis (GS). Swelling and intracellular vacuolation of the visceral epithelial cells (VEC) were considered as VECD. FSGS-lesions were seen most frequently in the glomeruli injected with 10 nl of a saponin solution with a concentration higher than 0.3 mg/ml. In view of the light microscopic lesions four glomeruli in a 0 mg/ml, the 0.1 mg/ml and the 0.6 mg/ml saponin groups were examined after 40 minutes with transmission electron microscopy (TEM) to evaluate the selectivity of the lesions. In the 0 and 0.1 mg/ml group only occasional limited fusion of the foot processes of the podocytes was seen. In the 0.6 mg/ml group segmental lysis of the VEC without ultrastructural damage to the capillary basement membrane or the endothelial and mesangial cells was seen. It is concluded that it is possible to induce direct segmental lysis of the visceral epithelial cells in a single glomerulus, and that this damage to the visceral epithelial cells is related to the development of focal and segmental glomerulosclerosis.

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