Increased excretion of urinary podocytes in lupus nephritis

Abstract

Podocytes are highly specialized epithelial cells that form part of the filtration barrier in the kidney, and their loss reflects a malfunction in glomerular filtration, which is usually associated with the progression of the disease. Glomerulonephritis is a serious complication that develops in about 50% of the lupus patients and is characterized by proteinuria arising from direct or indirect podocyte injury. To assess the possible role of podocytes in the pathogenesis of lupus nephritis (LN). Urinary and glomerular podocytes were detected in the kidney biopsies of patients (n = 17) with lupus nephritis, and from control biopsies obtained during autopsies. The WT-1 protein was used as a podocyte marker. The cumulative excretion of urinary podocytes was detected in the urinary sediments of LN patients and normal healthy controls, and the specimens were analyzed by immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay. The apoptotic index was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Gross proteinuria in lupus patients was determined via 24-hour urine samples, and the results were analyzed by Student t test. Biopsy specimens from 17 patients with class-III or IV LN had lower levels of glomerular WT-1 expression than the levels found in normal kidneys (P < 0.0001). The reduction of glomerular podocytes in patients with lupus nephritis correlated with the cumulative excretion of urinary podocytes (P < 0.0001) and proteinuria. There was no correlation between the urinary podocytes and the apoptotic index in the LN urinary sediments. A decrease in glomerular podocytes is associated with their cumulative excretion in urinary sediments; therefore, such findings correlate with proteinuria in lupus nephritis patients.

Keywords: Lupus nephritis; WT-1 marker; podocytes; proteinuria.

Figure 1

Proliferative changes assessed by the proliferating cell nuclear antigen (PCNA) in Lupus Nephritis (LN). Superior panel stained by H and E. Inferior panel, immunohystochemistry for PCNA. a and d: Control biopses. b and e: Class III nephritis. c and f: Class IV nephritis (40×).

Figure 2

Podocytes detected by immunofluorescent WT-1 expression in the glomeruli. Control tissues are represented in the left panel staining in blue by DAPI; the center panel shows the WT-1 podocytes marked in green, and the right panel shows a merged figure, where the podocytes are tagged in turquoise. The upper panel shows the control tissue, and the lower panel shows a representative lupus nephritis biopsy (40×)