Urinary and glomerular podocytes in patients with chronic kidney diseases.

BACKGROUNDS: Podocytes are highly differentiated epithelial cells involved in glomerular filtration. This study determines the clinical and histological significance of podocyte detachment and excretion in urine in patients with chronic kidney diseases. METHODS: Renal biopsy was performed in 59 patients (30 males, 29 females; mean age 48 ± 2 years), including 24 patients with immunoglobulin (Ig)A nephropathy, six each with focal segmental glomerulosclerosis, membranous nephropathy, and minimal change nephrotic syndrome, and 17 with other renal disorders. The number of glomerular podocytes and severity of morphological damage were evaluated in renal biopsy samples. Urinary podocytes were detected by anti-human podocalyxin antibody. The urinary IgG/albumin ratio and urinary peroxide products were assessed by gel electrophoresis and the 2',7'-dichlorodihydrofluorescein-diacetate method, respectively. RESULTS: A decrease in glomerular podocytes was associated with age (r = -0.33; P < 0.05), glomerulosclerosis (r = -0.43; P < 0.01), tubulointerstitial lesions (r = -0.46; P < 0.01), and low estimated glomerular filtration rates (r = 0.32; P < 0.05). Increased urinary podocyte excretion correlated with proteinuria (r = 0.36; P < 0.01), and was observed more frequently in patients with active histological lesions. Podocyte loss correlated with lower selectivity of proteinuria in patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis (r = -0.90; P < 0.001). Moreover, urinary peroxide products increased in association with glomerulosclerosis (r = 0.39; P < 0.05). CONCLUSIONS: Urinary podocyte excretion reflects ongoing glomerular injury in various kidney diseases, and podocyte loss correlated with glomerulosclerosis and impaired selectivity of proteinuria.

The resistive index is a marker of renal function, pathology, prognosis, and responsiveness to steroid therapy in chronic kidney disease patients.

To evaluate the significance of the renal resistive index (RI) as a noninvasive marker of renal histological damage and a prognostic indicator, we examined RI by Doppler ultrasonography in 202 chronic kidney disease (CKD) patients who underwent renal biopsy. RI increased as the CKD stage progressed and correlated with age, systolic blood pressure, estimated glomerular filtration rate (eGFR), and renal histological changes, including glomerulosclerosis, arteriolosclerosis, and tubulointerstitial damage. Prognostic evaluation with a median follow-up period of 38.5 months revealed that patients with RI ≥ 0.7 (high RI group, n = 39) had significantly poorer renal survival than those with RI < 0.65 (normal RI group, n = 120) and 0.65 ≤ RI < 0.7 (high-normal RI group, n = 43). The patients in the high-normal RI group showed good response to steroids. However, in the high RI group, steroid therapy did not significantly improve renal survival. Of the clinical indices studied, RI ≥ 0.7, hypertension, proteinuria, and low eGFR at diagnosis were independent risk factors for worsening renal dysfunction. In conclusion, RI in CKD patients was considered as a marker of renal function, histological damage, and renal prognosis, and a possible determinant of indication for steroids.

Detection of myeloperoxidase in membranous nephropathy-like deposits in patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis is usually classified as a pauci-immune type. However, it sometimes shows immune complex deposition of unknown origin. We examined the glomerular localization of myeloperoxidase by double immunofluorescence and immunoelectron microscopy in cases of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis with membranous nephropathy-like immunoglobulin G deposition to investigate the immune complex antigens in these cases. Six (35%) of the biopsy samples from 17 cases with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis showed granular deposition of immunoglobulin G along the glomerular capillary walls. Light microscopy revealed necrotizing crescentic glomerulonephritis with segmental thickening of the glomerular basement membrane. Electron microscopy showed electron-dense deposits in intramembranous and mesangial areas. However, the size and distribution of the deposits were irregular and segmental in the examined cases, unlike typical global and subepithelial lesions of membranous nephropathy. Double immunofluorescence using Alexa Fluor 594-labeled anti-myeloperoxidase antibody and fluorescein isothiocyanate-labeled anti-immunoglobulin G antibody, as well as immunoelectron microscopy using anti-myeloperoxidase antibody labeled with 25-nm gold particles revealed partial colocalization of myeloperoxidase and immunoglobulin G within the glomerular basement membrane and mesangium. In some cases of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, myeloperoxidase may form immune complexes and develop membranous nephropathy-like lesions.