Similar incidence of graft glomerulonephritis in recipients with definitively diagnosed glomerulonephritis and those with unknown etiology: a retrospective observational study.

OBJECTIVE: In China, most of the patients who underwent kidney transplants have unknown causes of end-stage renal disease (uESRD). However, little is known regarding the incidence of graft glomerulonephritis (GN) and graft survival in kidney transplant recipients (KTRs) with uESRD. METHODS: In this retrospective cohort study, 473 of the 565 KTRs who underwent kidney transplantation (KTx) from 2015 to 2020 were included. We mainly observed the occurrence of graft GN between uESRD group and definitively diagnosed GN group, and repeatedly compared after propensity score matching (PSM). RESULTS: The median follow-up was 50 months in 473 KTRs, and about 75% of KTRs of native kidney disease of unknown etiology. The total cumulative incidence of graft GN was 17%, and no difference was observed between the definitively diagnosed GN group and the uESRD group (p = 0.76). Further, PSM analysis also showed no difference in the incidence of graft GN between the 2 groups. Multivariable analysis disclosed males (p = 0.001), younger age (p = 0.03), and anti-endothelial cell anti-body (AECA) positive pre-KTx (p = 0.001) were independent risk factors for graft GN. CONCLUSIONS: The incidence of graft GN was similar between uESRD and definitively diagnosed GN group. The allograft survival was also similar between two groups.

Poor outcomes of proliferative glomerulonephritis with monoclonal IgG deposits in renal allografts: a retrospective multicenter study.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) in renal allografts is a rare, renal-limited disease. No study has reported the long-term outcomes and prognostic features of PGNMID in renal allografts in the Chinese population. METHODS: We retrospectively included transplant patients diagnosed with PGNMID who underwent renal allograft biopsy at three transplant centers from April 2012 to July 2020. We observed the clinicopathologic features, explored the long-term graft survival, and investigated the characteristics associated with the prognosis. RESULTS: A total of 13 transplant patients with PGNMID were included, out of 3821 biopsies. The mean follow-up time was 55 months since kidney transplantation (KTx). At diagnosis, all patients presented with proteinuria (100%) and most of them with hematuria (92%). IgG3κ (69%) was the main immunofluorescence (IF) subtype. The median graft survival of the total cohort was 17 months from diagnosis and 49 months from kidney transplantation. During follow-up, 9 patients needed dialysis and 2 out of 9 patients who progressed to dialysis died of infection. Primary membranoproliferative glomerulonephritis (MPGN) (P = 0.014) and MPGN pattern at diagnostic biopsy (P < 0.001) were associated with a higher risk of graft loss. CONCLUSIONS: The long-term outcome of allograft PGNMID was relatively poor in the Chinese population. Primary MPGN and MPGN pattern in renal allograft were associated with  poor outcomes.

Conversion from mycophenolate mofetil to mizoribine in the early stages of BK polyomavirus infection could improve kidney allograft prognosis: a single-center study from China.

BACKGROUND: Some studies have suggested mizoribine (MZR) could inhibit the replication of BK polyomavirus (BKPyV). The purpose of this study was to explore whether conversion from mycophenolate mofetil (MMF) to MZR in the early stages of BKPyV infection can improve kidney allograft prognosis. METHODS: Twenty-one kidney transplant recipients with BKPyV viruria/viremia and ten with BK polyomavirus-associated allograft nephropathy (BKPyVAN) received MZR conversion therapy were retrospectively identified. The clearance rate of urine and blood BKPyV DNA, change of serum creatinine (SCr), uric acid (UA), hemoglobin (HB), white blood cell (WBC), lymphocyte ratio, platelet (PLT), routine urinalysis, panel reactive antibody (PRA), and gastrointestinal disorders during follow-up of the 2 groups were evaluated and compared. RESULTS: After MZR conversion therapy, the clearance rate of urine and blood viral load in BKPyV viruria/viremia group were 85.7 and 100 %, while that in BKPyVAN were 40 and 87.5 %, respectively. Stable SCr were observed in all cases of BKPyV viruria/viremia group, while that of BKPyVAN was only 40 % (P < 0.001) and one even progressed to end-stage renal disease. The results of routine urinalysis in the two groups showed no significant changes before and after MZR conversion therapy. However, in BKPyV viruria/viremia group, four cases developed acute rejection and one had positive PRA-II but no donor specific antibody, requiring conversion back to MMF. Hyperuricemia was the common adverse effect of MZR. CONCLUSIONS: Conversion from MMF to MZR could help clear BKPyV infection. As compared to BKPyVAN, patients who underwent initiation of MZR conversion therapy in the early stages of BKPyV infection maintained stable allograft function. Prospective studies with larger sample size are needed to ascertain this preliminary finding.

Donor-derived cell-free DNA: An independent biomarker in kidney transplant patients with antibody-mediated rejection.

INTRODUCTION: Antibody-mediated rejection (ABMR) is a major cause of kidney transplant failure which requires donor-specific antibodies (DSA) for a definitive diagnosis. Donor-derived cell-free DNA (ddcfDNA) is an emerging biomarker used to assess kidney allograft injury. However, current data is limited to predict the accuracy of ddcfDNA in ABMR diagnosis. This study was conducted to compare the performance of DSA with plasma ddcfDNA for the diagnosis of ABMR. METHODS: In this retrospective single-center observational study, we enrolled 50 kidney transplant recipients who were diagnosed with the suspicion of rejection between June 2018 and May 2019 at the Jinling Hospital. Plasma ddcfDNA was measured by using a novel target region capture sequencing methodology. A total of 37 patients who were tested with DSA and biopsy were divided into four subgroups (ABMR+/DSA+, ABMR+/DSA-, ABMR-/DSA+, ABMR-/DSA-) for the distribution of ddcfDNA (%) by ABMR and DSA. RESULTS: The median level of ddcfDNA in biopsy showed that the ABMR group (1.66%, IQR 1.34-3.76%) was significantly higher than the median level (0.63%, IQR 0.43-0.74%) in non-ABMR (p < 0.001). With a ddcfDNA cutoff of 0.96%, the AUC was 0.90 (95%CI, 0.86-0.95), which was associated with a sensitivity of 90.5% (95%CI, 69.6-98.8%) and specificity of 96.6% (95%CI, 82.2-100%), a PPV of 95% (95%CI, 73.4-99.2%) and NPV of 93.3% (95%CI, 78.9-98.1%) were also observed. Among the four subgroups, ddcfDNA had no significant difference in both DSA+ group and DSA-group (p > 0.05). In the diagnosis of ABMR, the specificity, sensitivity, PPV and NPV of DSA were 50%, 74.1%, 41.7%, 80%, respectively. CONCLUSIONS: ddcfDNA levels in the blood could highly distinguish (biopsy-supported) ABMR occurrence, irrespective of whether this method is accompanied by DSA or not.

Endowing polyetheretherketone with anti-inflammatory ability and improved osteogenic ability.

Both osteogenesis and anti-inflammatory bioactive materials play a vital role in the regeneration of skeletal defects. Bone inflammation is hard to cure and can lead to malformation or amputation. The purpose of this study is to use anti-inflammatory drugs to endow polyetheretherketone (PEEK) with the dual ability to achieve anti-inflammatory effects while maintaining favorable biocompatibility. In this experiment, the porous PEEK was immersed in an aspirin (ASP) solution after sulfonation, and the obtained porous PEEK had significantly improved the anti-inflammatory abilities. Additionally, grafting the bone forming peptide (BFP) onto the porous PEEK can distinctly enchance the osteogenesis capability. The effects of the BFP polypeptide on the proliferation of MC3T3-E1 cells and ALP activity, and the effects of aspirin on inflammation were systematically investigated. The modified material showed favorable biocompatibility and osteogenic ability. The results suggest that the combination of the BFP polypeptide with aspirin may lead to a synergetic effect on the stimulation of osteogenesis and on the reduction of inflammation.

MXene-Based Hydrogels Endow Polyetheretherketone with Effective Osteogenicity and Combined Treatment of Osteosarcoma and Bacterial Infection.

After an osteosarcoma resection, the risks of cancer recurrence, postoperative infection, and large bone loss still threaten patients' health. Conventional treatment relies on implanting orthopedic materials to fill bone defects after surgery, but it has no ability of destroying residual tumor cells and preventing bacterial invasion. To tackle this challenge, here, we develop a novel multifunctional implant (SP@MX/GelMA) that mainly consists of MXene nanosheets, gelatin methacrylate (GelMA) hydrogels, and bioinert sulfonated polyetheretherketone (SP) with the purpose of facilitating tumor cell death, combating pathogenic bacteria, and promoting osteogenicity. Because of the synergistic photothermal effects of MXene and polydopamine (pDA), osteosarcoma cells are effectively killed on the multifunctional coatings under 808 nm near-infrared (NIR) irradiation through thermal ablation. After loading tobramycin (TOB), the SP@MX-TOB/GelMA implants display robust antibacterial properties against Gram-negative/Gram-positive bacteria. More importantly, the multifunctional implants are demonstrated to have superior cytocompatibility and osteogenesis-promoting capability in terms of cell replication, spreading, alkaline phosphatase activity, calcium matrix mineralization, and in vivo osseointegration. Accordingly, such photothermally controlled multifunctional implants not only defeat osteosarcoma cells and bacteria but also intensify osteogenicity, which hold a greatly promising countermeasure for curing postoperative tissue lesion from an osteosarcoma excision.

Two-dimensional MXene/cobalt nanowire heterojunction for controlled drug delivery and chemo-photothermal therapy.

Two-dimensional (2D) MXene nanomaterials have explored as a great potential candidate for tumor therapy during recent decades, especially for photothermal therapeutic applications. However, MXene-based drug-carriers cannot be elaborately controlled in cancer therapy. To solve the problem, a heterostructured titanium carbide-cobalt nanowires (Ti3C2-CoNWs) nanocarrier is developed for synergetic anticancer with magnetic controlling ability, dual stimuli-responsive drug release, and chemo-photothermal therapy. The structure, drug loading/release behavior, magnetic controlling capacity, photothermal performance, and synergistic therapeutic efficiency of the Ti3C2-CoNWs nanocarrier heterojunction are investigated. The heterostructured Ti3C2-CoNWs nanocarrier exhibits excellent photothermal conversion efficiency under 808 nm laser irradiation and high drug loading ability (225.05%). The doxorubicin (DOX) release behavior can be triggered by acid pH value (4-6) or near-infrared (NIR) irradiation. The Ti3C2-CoNWs nanocarrier heterojunction with synergistic chemo-photothermal therapeutic effect exhibits strong lethality for cancer cells than that of chemotherapy or photothermal therapy (PTT) alone. Therefore, Ti3C2-CoNWs nanocarrier heterojunction will be a promising choice for improving the efficiency of cancer treatment.

The immunophenotyping of different stages of BK virus allograft nephropathy.

Objectives: To investigate the immunohistochemical features of different stages of BK virus allograft nephropathy (BKVN) and further elucidate the underlying immunological mechanism involved in the evolution of BKVN. Methods: Fifty-two renal transplant recipients with biopsy proven BKVN were retrospectively selected. According to the third edition of the American Society of Transplantation Infection guidelines, 10 patients were categorized as having mild BKVN (stage A), 25 were moderate (stage B) and 17 were severe (stage C). The differential infiltrations of CD3+ (T lymphocytes), CD4+ (helper T lymphocytes), CD8+ (cytotoxic T lymphocytes), CD20+ (B lymphocytes), CD68+ (macrophages) and CD138+ (plasma cells) cells and the expression of interleukin-2 receptor (IL-2R) and human leukocyte antigen DR (HLA-DR) were compared among the three groups. Results: CD3+, CD4+, CD8+, CD20+, CD138+ and CD68+ cells infiltrations, IL-2R and HLA-DR expression were positive in the BKVN patients. Moreover, with increasing stages of BKVN, the numbers of positively stained inflammatory cells and the expression of IL-2R were significantly increased in the severe group compared to the mild group, whereas no statistically significant differences were observed with regard to HLA-DR expression. Eosinophil and neutrophil infiltration could also be observed in moderate to advanced BKVN. Conclusion: Renal allograft damage caused by BKVN involved T lymphocyte-, B lymphocyte- and mononuclear macrophage-mediated immune responses. Inflammatory cell infiltrations in the renal allograft were probably the driving force for BKVN progression. Additionally, eosinophils and neutrophils may be involved in the pathophysiological mechanism of BKVN.

Histopathologic Features that Predict Transplant Glomerulopathy Progression in a Chinese Cohort.

BACKGROUND: Transplant glomerulopathy (TG) represents a major cause of long-term allograft failure and is the leading cause of overall post-transplant proteinuria. The extent to which histopathologic features predicts prognostication is uncertain. METHODS: A single-center retrospective cohort with biopsy-proven TG was investigated. Renal biopsies were scored according to Banff 2017. The primary outcome was death-censored graft failure defined as return to dialysis or estimated glomerular filtration rate (eGFR) decreased to <15 mL/min/1.73 m2. The prognostic significance of clinical and histopathologic parameters was determined using Cox proportional hazards models. RESULTS: Data from 180 cases were available for analysis with a median follow-up of 5.0 (2.6-8.2) years. In multivariable models, ci + ct score (HR 3.1; 95% CI 2.0-4.9), cg score (HR 1.7; 95% CI 1.1-2.8), eGFR (HR 2.1; 95% CI 1.4-3.2) and proteinuria (HR 2.4; 95% CI 1.6-3.7) were independent predictors of the primary outcome. Mesangial Immunoglobulin A deposition did not significantly affect allograft survival. The only significant pathologic factors for the severity of proteinuria were cg and g + ptc (adjusted R2 = 0.46) as determined by multivariable stepwise linear regression analysis. CONCLUSIONS: Severe ci + ct and cg at biopsy were predictors of unfavorable allograft prognosis in TG patients even after taking into consideration clinical characteristics. Histologic severity of cg and g + ptc was significantly associated with clinical proteinuria.

Dual Therapy Coating on Micro/Nanoscale Porous Polyetheretherketone to Eradicate Biofilms and Accelerate Bone Tissue Repair.

Defective osteogenesis and latent infections continue to be two major issues in the therapy of bone tissue regeneration. In this study, a unique hierarchically micro/nanoscale-architecture is first proposed and produced on polyetheretherketone (PEEK). Besides, a "simvastatin-PLLA film-tobramycin microspheres" delivery system is subsequently fabricated to endow the PEEK implant with osteogenic and antibacterial capabilities. In vitro antibacterial evaluations confirm that the decorated PEEK scaffolds possess excellent resistance against planktonic/adherent bacteria. In vitro cell attachment/proliferation, lactate dehydrogenase (LDH) content, alkaline phosphatase (ALP) activity, calcium mineral deposition experiments, and real-time PCR analysis all exhibit that the superior proliferation rate and osteo-differentiation potential of MC3T3-E1 pre-osteoblasts are presented on the PEEK samples with dual functional decoration. In the mouse calvarial defect model, the micro-CT and histological results demonstrate that our scaffolds display a remarkable bone forming capability. Generally, the PEEK scaffolds co-endowed with simvastatin and tobramycin microspheres possess great potential in clinics.

Simvastatin delivery on PEEK for bioactivity and osteogenesis enhancements.

A strategy developed for obtaining positive cellular responses remains to be focused in the filed of functional biomimetics. In this study, a hydrogel covered simvastatin-loaded polyetheretherketone (PEEK) bio-composites was constructed with the purpose of bone tissue regeneration therapy. Briefly, a three-dimensional (3D) porous structure was fabricated on PEEK surface; then the substrate was functionalized with the poly(L-lactic acid)/simvastatin porous film and hyaluronic acid hydrogel subsequently. In vitro cell attachment, proliferation, and cytoskeletal observation experiments reveal that our scaffolds show better bio-affinity due to the layer of hyaluronic acid hydrogel compared with control. Furthermore, the alkaline phosphatase activity, calcium mineral deposition evaluation, and gene expression for osteogenic potential all exhibit that the superior osteogenic differentiation of MC3T3-E1 pre-osteoblasts on our scaffolds. Therefore, our PEEK samples loaded with simvastatin and covered with hyaluronic acid hydrogel hold great potential in clinical applications for bone repair.

Nomogram predicts survival benefit for non- metastatic esophageal cancer patients who underwent preoperative radiotherapy.

BACKGROUND: A prognostic model to predict the individual disease-specific survival (DSS) rates of non-metastatic esophageal cancer (nMEC) patients after preoperative radiotherapy (pRT) has not been established. In the current study, we aimed to establish a survival nomogram for nMEC patients after pRT. METHODS: We identified 2,424 nMEC patients who underwent pRT from the Surveillance, Epidemiology, and End Results database. Approximately, 80% (n=1,948) of the included patients were randomly selected and designated as training data set, and the remaining patients (n=476) were defined as external validation set. Nomogram was established by the training set and validated by the validation set. RESULTS: According to the results of the multivariate analysis, a nomogram combined with age at diagnosis, sex, tumor location, yp-T stage, yp metastatic lymph node ratio stage (yp-mLNRS), and grade was developed. The C-index of the model was significantly higher than that of yp-TNM staging system (0.62, 95% CI, 0.58 to 0.66 vs 0.55, 95% CI, 0.51 to 0.60; p<0.001). Calibration plots of the nomogram showed that the probability of DSS rates optimally corresponded to the survival rates were observed. CONCLUSION: The proposed nomogram resulted in more reliable DSS prediction for nMEC patients in general population, regardless of the patient's histological type. Upon validation, it will aid in individualized survival prediction and prove useful in clinical decision making in nMECs after pRT.

Risk factors for BK virus infection in living-donor renal transplant recipients: a single-center study from China.

OBJECTIVES: BK virus (BKV) infection has become one of the main complications in renal transplant recipients (RTRs) with the arrival of newer potent immunosuppressive agents. However, reports on the epidemiology of BKV infection and risk factors in Chinese population after renal transplantation are scarce. METHODS: From June 2015 to July 2016, living-donor renal transplant recipients (LDRTRs) who routinely received the quantitative BKV DNA testing of urine and plasma samples using quantitative real-time polymerase chain reaction (PCR) for the first time after transplantation were selected, while dialysis patients and healthy living donors during that period served as controls. Potential variables were compared and analyzed using logistic regression model multivariate analysis to assess the BKV infection related factors in LDRTRs. RESULTS: Among the 52 LDRTRs identified, BKV DNA was detected in 16 urine samples (30.8%), significantly higher than that of dialysis patients (6.3%) and healthy living donors (4.2%) (p < .001). Nevertheless, no statistically significant difference wax noted between the latter two groups in urine samples (p = .842). Meanwhile, BKV DNA detection in blood samples was all negative in the three groups. Univariate analysis shown tacrolimus (Tac) trough level and lymphocyte percentage were associated with BKV infection in LDRTRs. Multivariate regression analysis also showed Tac trough level (HR, 1.644; p = .03), lymphocyte percentage (HR, 0.878; p = .026) were associated with BKV infection in LDRTRs. CONCLUSIONS: In Chinese population, the incidence of BKV infection increased significantly after living-donor renal transplantation. Significantly increased Tac trough level and decreased lymphocyte percentage might be the risk factors for BKV infection in LDRTRs.

Controlling Cellular Volume via Mechanical and Physical Properties of Substrate.

The mechanical and physical properties of substrate play a crucial role in regulating many cell functions and behaviors. However, how these properties affect cell volume is still unclear. Here, we show that an increase in substrate stiffness, available spread area, or effective adhesion energy density results in a remarkable cell volume decrease (up to 50%), and the dynamic cell spreading process is also accompanied by dramatic cell volume decrease. Further, studies of ion channel inhibition and osmotic shock suggest that these volume decreases are due to the efflux of water and ions. We also show that disrupting cortex contractility leads to bigger cell volume. Collectively, these results reveal the "mechanism of adhesion-induced compression of cells," i.e., stronger interaction between cell and substrate leads to higher actomyosin contractility, expels water and ions, and thus decreases cell volume.

A facile synthesis of a cobalt nanoparticle-graphene nanocomposite with high-performance and triple-band electromagnetic wave absorption properties.

Ferromagnetic metal nanoparticle/graphene nanocomposites are promising as excellent electromagnetic (EM) wave absorption materials. In this work, we used a facile method to synthesize a cobalt nanoparticle-graphene (CoNP-G) nanocomposite. The obtained CoNPs-G exhibited a saturation magnetization (M s) of 31.3 emu g-1 and a coercivity (H C) of 408.9 Oe at 298.15 K. In particular, the CoNPs-G nanocomposite provided high-performance EM wave absorption with multiband, wide effective absorption bandwidth, which was mainly attributed to the synergy effects generated by the magnetic loss of cobalt and the dielectric loss of graphene. In the range of 2-18 GHz, the sample (55 wt% CoNPs-G) held three effective reflection loss (RL) peaks (frequency ranges of 2.4-3.84, 7.84-11.87 and 13.25-18 GHz, respectively, RL ≤ -10 dB) with the coating thickness of 4.5 mm, and the effective bandwidth reached the maximum of 10.22 GHz, and the minimal RL reached -40.53 dB at 9.50 GHz. Therefore, the CoNPs-G nanocomposite presents a great promising application in the electromagnetic wave absorption field.

AgNPs-decorated 3D printed PEEK implant for infection control and bone repair.

Polyetheretherketone (PEEK) is an ideal substitute material for bone tissue engineering, which can avoid the stress shielding phenomenon due to its similar mechanical properties to natural human bone. Complex bone defect and postoperative infection are still two enormous challenges in orthopedic clinics. It's well-known that additive manufacturing possesses the merits of high-precision and rapid prototyping, thus it easily meets the needs of mold processing. In the present study, we developed a novel Ag-decorated 3D printed PEEK via catecholamine chemistry. SEM image showed that silver nanoparticles (AgNPs) were evenly anchored on the surface. The following antibacterial tests, including bacterial inhibition ring, bacterial dynamics curves and antibiofilm test, indicated that the Ag-decorated 3D PEEK scaffolds displayed significant antibacterial effect towards Gram-negative and Gram-positive bacteria. Then MG-63 cells were seeded on samples for cell proliferation and ALP activity tests. The results demonstrated the scaffold modified with AgNPs could support cell proliferation, and enhanced higher alkaline phosphatase activity compared with pure PEEK scaffold. Expectedly, this dual functional 3D material holds great potential application in clinical bone tissue repair.

Synthesis and catalytic application of magnetic Co-Cu nanowires.

A rapid, template-free method was developed to prepare magnetic, bimetallic Co-Cu nanowires via liquid phase reduction and metal replacement under an external magnetic field. The characterization results confirmed that the as-prepared product was bimetallic Co-Cu nanowires with a desirable linear structure. Additionally, the magnetic hysteresis loop showed that the bimetallic Co-Cu nanowires were paramagnetic, which meant they could be easily separated from the reaction mixture. Furthermore, they were applied to the hydrolysis system of ammonia borane as a catalyst for the first time. More importantly, the catalysis results showed that the bimetallic nanowires possessed appealing catalytic performance. Therefore, a rapid and facile synthesis method is introduced which is capable of preparing bimetallic Co-Cu nanowires with great potential for industrial applications.

High efficiency fabrication of complex microtube arrays by scanning focused femtosecond laser Bessel beam for trapping/releasing biological cells.

In this paper, we present a focused femtosecond laser Bessel beam scanning technique for the rapid fabrication of large-area 3D complex microtube arrays. The femtosecond laser beam is converted into several Bessel beams by two-dimensional phase modulation using a spatial light modulator. By scanning the focused Bessel beam along a designed route, microtubes with variable size and flexible geometry are rapidly fabricated by two-photon polymerization. The fabrication time is reduced by two orders of magnitude in comparison with conventional point-to-point scanning. Moreover, we construct an effective microoperating system for single cell manipulation using microtube arrays, and demonstrate its use in the capture, transfer, and release of embryonic fibroblast mouse cells as well as human breast cancer cells. The new fabrication strategy provides a novel method for the rapid fabrication of functional devices using a flexibly tailored laser beam.

HLA-DR, and not PLA2R, is expressed on the podocytes in kidney allografts in de novo membranous nephropathy.

Idiopathic membranous nephropathy (IMN) is known to be associated with antibodies acting on the M-type phospholipase A2 receptor (PLA2R) of the podocyte. However, the mechanism underlying de novo membranous nephropathy (dn MN) posttransplantation remains unclear. In this study, we aimed to elucidate the mechanism underlying dn MN.We selected 8 cases with dn MN and compared them to 20 IMN cases. Fifteen cases of stable grafts were selected as controls.Several differences between the dn MN group and the IMN group were detected. IgG4 showed negligible positive staining in patients with dn MN, while it was predominant in the IMN group (1/8 vs 20/20, P < 0.001). Serum anti-PLA2R antibodies and anti-PLA2R antibodies of the podocyte were very few in the dn MN patients; however, these antibodies were detected in most of the IMN patients (serum anti-PLA2R antibodies: 1/8 vs 16/20, P = 0.002, anti-PLA2R antibodies of the podocyte: 0/8 vs 17/20, P < 0.001). The dn MN patients also showed higher ratio of interstitial inflammation, peritubular capillaritis, and peritubular capillary C4d deposition. Importantly, human leukocyte antigens (HLA)-DR expression was detected on the podocytes in most of the dn MN patients, but none of the IMN patients and stable graft patients showed HLA-DR expression.These data suggested that the PLA2R pathway, which is known to play a role in IMN, was not involved in the mechanism underlying dn MN. On the contrary, dn MN might be associated with the alloimmune response directed against the podocyte.