Background/Purpose: Podocytes are glomerular visceral epithelial cells functioning as molecular sieves not to allow high molecular weight protein to leak from glomerular capillary wall. The decreased number of podocyte per glomerulus due to death or detachment from glomerular basement membrane leads to severe proteinuria, irreversible glomerulosclerosis and end stage kidney disease. Podocalyxin (PCX) is one of the podocyte markers, expressed on the apical cell membrane and shed in urine from injured podocytes. It has been reported that two different urine PCX-related biomarkers, urine numbers of PCX-positive cells (podocytes) and urine levels of PCX are associated with glomerular lesions, such as in IgA nephropathy and diabetic nephropathy. However, the role of these biomarkers in systemic lupus erythematosus (SLE) and ANCA-associated vasculitis (AAV) remain to be elucidated. Methods: Urine numbers of podocytes (U-Pod) were determined by counting PCX-positive cells in sediments from urine samples. PCX staining was done by indirect immunofluorescent method. Urine levels of PCX (U-PCX) were measured by sandwich ELISA, normalized to urine creatinine levels. Patients with proteinuria (defined as more than 0.2 urine protein/creatinine ratio) and/or renal failure (defined as estimated GFR less than 60 mL/min/1.73m²) were defined as KD(+), and patients who had neither proteinuria nor renal failure were defined as KD(-). Patients with SLE and AAV were recruited from our hospitals between October 2010 and March 2013. SLE-KD(+) (n=61), SLE-KD(-) (n=22), AAV-KD(+) (n=17) and AAV-KD(-) (n=6). Renal histology of lupus nephritis was classified according to ISN/RPS classification. Statistical analysis was done using Mann-Whitney test. P<0.05 was defined as statistical significance. Each value was described as mean ± standard deviation. Results: U-Pod was significantly higher in the KD(+) group than in the KD(-) group both in SLE (7.9±24.9 vs 0.2±0.6 cells/mL, P<0.0001) and in AAV (0.7±1.0 vs 0.0±0.0 cells/mL, P=0.0048). However, there was not a statistical difference in U-Pod between the SLE-KD(+) group and the AAV-KD(+) group (P=0.397). In contrast, although U-PCX was significantly higher in the KD(+) group than in the KD(-) group in SLE (362.2±298.8 vs 128.9±113.5 μg/gCr, P=0.0012),  U-PCX tended to be lower in the KD(+) group than in the KD(-) group in AAV (100.3±117.6 vs 206.3±169.5 μg/gCr, P=0.06). In addition, U-PCX was significantly higher in the SLE-KD(+) group than in the AAV-KD(+) group (P<0.0001). Among 36 patients with biopsy-proven lupus nephritis, U-Pod was significantly higher in patients with Class IV lesion (diffuse proliferative lesion) than in those without Class IV lesion (20.0±38.6 vs 0.7±0.6 cells/mL, P=0.0025). U-PCX tended to be higher in patients with Class V lesion (membranous lesion) compared to that in those without class V lesion (549.1±344.5 vs 347.8±274.0 cells/mL, P=0.058), although it did not reach statistical significance. Conclusion: Our data suggest that podocyte injury estimated by U-PCX is more severe in lupus nephritis compared to AAV nephritis. In addition, the combination of U-Pod and U-PCX may predict the histological features of lupus nephritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-urinary-podocyte-number-and-urinary-podocalyxin-level-as-biomarkers-of-glomerulonephritis-in-systemic-lupus-erythematosus-and-anca-associated-vasculitis/