Alteration of anti-PLA₂R reactivity in follow-up samples (n = 10).

<p>Anti-PLA₂R, anti-phospholipase A₂ receptor antibody; uPCR, urine protein-creatinine ratio.</p

Clinical outcomes of patients with idiopathic MN according to anti-PLA₂R levels.

<p>MN, membranous nephropathy; Anti-PLA₂R, anti-phospholipase A₂ receptor antibody; N, number of patients.</p>a<p>Group of patients whose serum samples showed anti-PLA₂R reactivity at dilutions of 1∶25 or 1∶100 with negative results at dilutions over 1∶100; ^bGroup of patients whose serum samples showed anti-PLA₂R reactivity at dilutions of 1∶500 or 1∶2000 with negative results at dilutions over 1∶2000; ^cGroup of patients whose serum samples showed anti-PLA₂R reactivity at dilutions up to 1∶8000.</p

Clinical outcomes and general characteristics of patients with idiopathic MN according to anti-PLA₂R reactivity.

<p>The data are expressed as the number (%) or median (25–75% interquartile range) or the mean±SD. MN, membranous nephropathy; Anti-PLA₂R, anti-phospholipase A₂ receptor antibody. eGFR, estimated glomerular filtration rate calculated using the Modification of Diet in Renal Disease formula; uPCR, urine protein-creatinine ratio; RAS blocker, renin angiotensin systemic blocker.</p

Clinical characteristics of patients with idiopathic MN at the time of kidney biopsy according to anti-PLA₂R reactivity.

<p>The data are expressed as the mean±SD or median (25–75% interquartile range). MN, membranous nephropathy; Anti-PLA₂R, anti-phospholipase A2 receptor antibody; eGFR, estimated glomerular filtration rate calculated using the Modification of Diet in Renal Disease formula; uPCR, urine protein-creatinine ratio; RAS blocker, renin angiotensin systemic blocker.</p

Relationship between anti-PLA₂R levels and clinical parameters in patients with idiopathic MN.

<p>A: Proteinuria was more severe in patients with higher anti-PLA₂R level. *Dunn’s multiple pairwise comparison test after Kruskal-Wallis test. B Severity of hypoalbuminemia was increased depending on the anti-PLA₂R levels. **ANOVA test with polynomial contrast. C: The proportion of patients with nephrotic range proteinuria was increased according to the anti-PLA₂R levels. <i>***</i> Mantel-Haenszel χ² test.</p

Histologic findings of patients with secondary MN.

<p>MN, membranous nephropathy; Anti-PLA₂R, anti-phospholipase A2 receptor antibody; HBV, hepatitis B virus; HCV, hepatitis C virus.</p

Effects of 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA) on renal expression of soluble epoxide hydrolase (sEH) in ischemia-reperfusion injury (IRI) in kidneys.

<p>A: Histological changes were consistent with the functional changes (×200). IRI induced tubular necrosis, consisting of disruption and sloughing of tubular epithelial cells. Arrows indicate necrotic tubules, and asterisks indicate tubular casts. Tubular injury was increased in disease-control mice compared to AUDA-treated mice. B: Expression was quantified by a renal pathologist in a blinded fashion (*<i>P</i><0.05). Scores ranged from 1–5, based on the percentage of tubules affected (1: <10%; 2: 10–25%; 3: 25–50%; 4: 50–75%; 5: >75%). C: sEH was expressed in the endothelium of intraglomerular capillary loops and peritubular capillaries. D and E: Ischemic injury induced the down-regulation of sEH, but AUDA administration had no effect on sEH expression. DAPI was used as counterstaining. <i>EPHX2,</i> gene encoding sEH.</p

Protective effects of soluble epoxide hydrolase (sEH) inhibitor on hypoxic damage via neovascularization.

<p>A: Hypoxia inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), VEGF receptor-2 (KDR), and erythropoietin (EPO) were enhanced by 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA) administration. (*<i>P</i><0.05 compared to sham; #<i>P</i><0.05 compared to sham; †<i>P</i><0.05 compared to ischemia-reperfusion injury (IRI) +vehicle). B: Hypoxia induced the down-regulation of sEH in human umbilical vein endothelial cells (HUVECs). Cells were incubated with or without AUDA (10 µM) under hypoxic (1% O₂) or normoxic conditions (20% O₂) for 24 h. Apoptosis of HUVECs was assessed by p53 expression. Hypoxia induced apoptosis in HUVECs, but AUDA treatment reduced apoptosis associated with enhancement of HIF-1α. DAPI was used for counterstaining (magnification, ×400). C and D: c-kit (CD117) expression decreased after IRI, but was amplified by AUDA administration (magnification, ×800). E: AUDA treatment significantly enhanced c-kit expression. Data represent the results of one of three independent experiments (<i>n</i> = 6 per group; †<i>P</i><0.05 compared to IRI+vehicle). F: AUDA treatment increased c-kit and KDR expression levels in HUVECs exposed to hypoxia.</p

Regulation of soluble epoxide hydrolase (sEH) activity by adamantyl alkyl urea-based sEH inhibitor (AUDA) in renal ischemia-reperfusion injury (IRI).

<p>A: Plasma epoxyoctadecenoic acid (EpOME) and dihydroxyoctadec-12-enoic acid (DHOME) levels were quantified to investigate the enzyme activity of sEH. B: 9,10-, 12,13-, and total EpOME plasma concentrations were significantly increased in response to AUDA in renal IRI. C: The EpOME/DHOME ratio was significantly increased (*<i>P</i><0.05 compared to sham+vehicle; #<i>P</i><0.05 compared to sham+AUDA; †<i>P</i><0.05 compared to IRI+vehicle).</p

Effects of soluble epoxide hydrolase (sEH) inhibitor on the pro-/anti-inflammatory microenvironment in injured kidneys.

<p>A: Proinflammatory cytokines TNF-α and MCP-1 were significantly suppressed, while IL-10 and TGF-β were enhanced by treatment with 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA), as shown by real-time PCR. B: The proinflammatory cytokine IL-6 was decreased and the regulatory cytokines IL-4 and IL-10 were augmented by AUDA, as shown by multiplex cytokine assay. (*<i>P</i><0.05 compared to sham; #<i>P</i><0.05 compared to sham; †<i>P</i><0.05 compared to IRI+vehicle). C: AUDA decreased the infiltration of inflammatory cells (macrophages (F4/80), lymphocytes (CD3), and neutrophils (MPO)) mainly trafficked in the interstitial area. D: AUDA attenuated the infiltration of macrophages/monocytes and T cells expressing CD3, as shown by flow cytometry. F4/80, marker for pan-macrophage; CD44, indicative marker for effector-memory T-cells; CD45, leukocyte common antigen; Gr1, myeloid differentiation antigen.</p