Abstract
Idiopathic membranous nephropathy (iMN) is considered an immune-mediated disease where circulating autoantibodies against podocyte targets (mainly the PLA2R) cause the deposition of in-situ subepithelial immune-complexes. The consequent podocyte damage may cause cell detachment in urine (Podocyturia-PdoU). PdoU has been assessed in different kidney diseases, but limited data are available in iMN. In this study all patients with a diagnosis of iMN between 15/12/1999–16/07/2014 were tested for PLA2R antibodies (Ab anti-PLA2R, ELISA kit) and PdoU by flow cytometry with anti-podocalyxin antibody. A semi-quantitative PdoU score was defined according to the percentage of podocalyxin positive cells normalized to the total volume of sample and set relative to the urine creatinine measured in the supernatant. PdoU was positive in 17/27 patients (63%; 1+ score in 6/27—22.2%, 2+ in 4/27—14.8%, 3+ in 2/27—7.4%, 4+ in 5/27—18.5%). Only 2/7 patients with complete remission showed a positive PdoU (1+) while all six patients without remission have significant PdoU. PdoU+ was statistically correlated with the absence of remission and Ab anti-PLA2R + (p < 0.05) but PdoU, analysed as a continuous variable, showed a non-linear correlation with proteinuria or PLA2R antibody levels also in the cohort of patients with two available PdoU tests. In conclusion, PdoU could be detected in iMN and seems to be associated with commonly considered markers of disease activity (proteinuria and Ab anti-PLA2R) with a non-linear correlation. Despite data should be confirmed in large and prospective cohorts, according to the podocyte depletion hypothesis PdoU may represent an early marker of immunological activation with potential prognostic utility.
Highlights
Idiopathic membranous nephropathy is considered an immune-mediated disease where circulating autoantibodies against podocyte targets cause the deposition of in-situ subepithelial immune-complexes
In this study we focused our attention on PdoU in patients with Idiopathic membranous nephropathy (iMN) correlating our findings to clinical outcome and Ab anti-PLA2R
Discussion iMN is defined as an immune-mediated disease where circulating auto-antibodies against podocyte targets[6] cause the deposition of in situ sub-epithelial immune-complexes[15]
Summary
Idiopathic membranous nephropathy (iMN) is considered an immune-mediated disease where circulating autoantibodies against podocyte targets (mainly the P LA2R) cause the deposition of in-situ subepithelial immune-complexes. PdoU+ was statistically correlated with the absence of remission and Ab anti-PLA2R + (p < 0.05) but PdoU, analysed as a continuous variable, showed a non-linear correlation with proteinuria or P LA2R antibody levels in the cohort of patients with two available PdoU tests. PdoU could be detected in iMN and seems to be associated with commonly considered markers of disease activity (proteinuria and Ab anti-PLA2R) with a non-linear correlation. In the majority of previously considered idiopathic MN (iMN, accounting 75–80% of all cases) circulating and implanted antibodies againt a constitutive podocyte receptor (Phospolipase A2 receptor; P LA2R) could be detected, and their levels correlate to disease activity, recovery and relapse[6,7]. In this study we focused our attention on PdoU (analysed by flow cytometry) in patients with iMN correlating our findings to clinical outcome and Ab anti-PLA2R
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