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.

An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis

“…Additionally, following the washes some slides were counterstained with 4′,6-diamidino-2-phenylindole (DAPI). Finally, the slides were mounted and examined using fluorescent microscopy [ 8 ].…”

Human Urine as a Noninvasive Source of Kidney Cells

“…For example, in patients with focal and segmental glomerulosclerosis (FSGS), podocyte loss increases in accordance to the level of injury and might be a marker of disease progression [ 11 , 14 ]. Besides FSGS, urinary podocytes have been detected during the acute phase of other diseases, such as Henoch-Schönlein nephritis [ 10 ], IgA nephropathy [ 10 ], lupus nephritis [ 9 , 15 , 16 ], and also diabetic nephropathy [ 17 ] and preeclampsia [ 18 ]. Moreover, it has been suggested that urinary excretion of podocytes might be helpful to discriminate between acute and chronic stages of glomerular damage [ 19 ].…”

Cytoplasmic Localization of WT1 and Decrease of miRNA-16-1 in Nephrotic Syndrome

“…The WT1 protein has been used as a biomarker of podocyte loss from glomeruli in kidney disease [ 30 , 31 ] and of the presence of damaged podocytes in urinary sediment [ 32 , 33 ]. In this work, we clearly observed a reduction of podocytes in renal biopsies of children with NS and the presence of podocytes in the urine, but the reason for such podocyte detachment is not clear.…”