Proteinuria is strongly associated with kidney disease progression but the mechanisms underlying podocyte handling of serum proteins such as albumin and IgG remain to be elucidated. We have previously shown that albumin and IgG are transcytosed by podocytes in vitro. In other epithelial cells, the neonatal Fc receptor (FcRn) is required to salvage albumin and IgG from the degradative pathway thereby allowing these proteins to be transcytosed or recycled. Here we directly examine the role of FcRn in albumin and IgG trafficking in podocytes by studying handling of these proteins in FcRn knockout (KO) podocytes in vitro and in a podocyte-specific FcRn knockout mice in vivo. In vitro, we find that knockout of FcRn leads to IgG accumulation in podocytes but does not alter albumin trafficking. Similarly, in vivo, podocyte-specific knockout of FcRn does not result in albumin accumulation in podocytes in vivo as measured by mean albumin fluorescence intensity whereas these mice demonstrate significant intraglomerular accumulation of IgG over time. In addition we find that podocyte-specific FcRn KO mice demonstrate mesangial expansion as they age and activation of mesangial cells as demonstrated by increased expression of α-smooth muscle actin. Taken together, these results suggest that trafficking pathways for albumin and IgG differ in podocytes and that sustained disruption of trafficking of plasma proteins alters glomerular structure.

Background: Multidrug-resistant (MDR) Acinetobacter baumannii has become a major threat of nosocomial infection worldwide. The study aimed to assess the incidence of bacteremia due to MDR A. baumannii, factors associated with the infection, and clinical outcomes.Methods: A retrospective study was conducted for evaluating 49 episodes of A. baumannii bacteremia in adult patients admitted to a university hospital in Northeast Thailand between 2005 and 2007. Comparison of the data between patients with susceptible A. baumannii bacteremia and those with MDR A. baumannii bacteremia was performed.Results: The incidence of MDR A. baumannii bacteremia was 3.6 episodes per 10 000 hospital admission. The mean (SD) age of the patients was comparable between the 2 study groups [56.9 (17.3) years in susceptible group and 59.4 (16.8) years in drug-resistant group]. Most of the patients had pre-existing diseases; cancer, chronic kidney disease, and diabetes mellitus were the 3 most common. The most common source of bacteremia was pneumonia. The significantly independent factors associated with MDR A. baumannii bacteremia were prior ICU admission (odds ratio (OR) 10.01, 95% confidence interval (CI) 1.39-72.20), prior beta-lactam/beta-lactamase inhibitor use (OR 8.06, 95%CI 1.39-46.64), and prior carbapenems use (OR 11.40,). Overall mortality rate was significantly higher in MDR group (48% vs. 91.7% in susceptible and MDR group, respectively, p = 0.001). The significantly independent factors related to mortality were APACHE II score (OR 1.25, 95%CI 1.03-1.52) and secondary bacteremia (OR 14.86,.Conclusion: This study revealed that the significantly independent factors associated with MDR A. baumannii bacteremia were prior ICU admission and prior use of broad spectrum antibiotics. This infection caused high mortality rate. Emphasize on prevention, strict application of infection control and appropriate use of antibiotic could reduce the risk and control this infection.

Background The information guiding the treatment decision(s) for renal diseases in systemic sclerosis (SSc) is the renal pathological finding. This study aimed to evaluate the renal pathological diagnosis and its clinical feature among SSc. Method A historical cohort study was performed on adult Thai SSc patients who underwent renal biopsy during January 2005–December 2016. The renal pathologic findings and patient clinical characteristics were reviewed. Chi-square or Fisher’s exact test was applied to analyze the association between clinical manifestation and renal pathology. Results Of the 26 SSc patients identified (77% female), 46% had the diffuse cutaneous SSc subtype. The mean age at the time of biopsy was 53.2±14.4 years and median duration of disease was 2.4 years (IQR 0.5–7.0). Rapidly progressive glomerulonephritis (RPGN) was the most common renal manifestation (53.9%) followed by nephrotic syndrome (19.2%) and nephritis (11.5%). The pathological diagnosis included lupus nephritis (LN) class IV (26.9%), LN class V (19.2%), scleroderma renal crisis (SRC; 19.3%), progressive renal disease in scleroderma (7.7%), and IgA nephropathy (7.7%). The nephrotic syndrome was the most common renal feature among LN class V patients, whereas RPGN was the commonest renal presentation among LN class IV and SRC patients ( p =0.001). Dialysis treatment at the time of kidney biopsy was significantly higher in SRC patients than in the other groups ( p <0.001). The SRC tended to have more frequent cardiac involvement, pulmonary fibrosis, and shorter disease duration than the other groups. Conclusion This is the first report of renal pathologic findings in Thai SSc patients. RPGN is the commonest renal manifestation among SSc who underwent kidney biopsy; for whom LN was the most common pathological finding. Nephrotic syndrome is a clinical feature of glomerular diseases other than renal involvement in SSc.

The neonatal Fc receptor (FcRn) has been shown to be required for antigen presentation in dendritic cells, and global knockout of FcRn attenuates immune-mediated kidney disease. Podocytes express interleukin-6 (IL-6) receptor and produce IL-6 under proinflammatory conditions. Here we examined the role of FcRn in the IL-6-mediated inflammatory response in podocytes. We examined IL-6 production by ELISA and expression by qPCR in wild type (WT) and FcRn knockout (KO) podocytes after treatment with proinflammatory stimuli as well as IL-6-mediated signaling via the JAK/STAT pathway. We also examined podocyte motility in cultured WT and KO podocytes after a proinflammatory challenge. We found that FcRn KO podocytes produced minimal amount of IL-6 after treatment with albumin, IgG, or immune complexes whereas WT podocytes had a robust response. FcRn KO podocytes also had minimal expression of IL-6 compared with WT. By Western blotting, there was significantly less phosphorylated STAT3 in KO podocytes after treatment with IFNγ or immune complexes. In a scratch assay, FcRn KO podocytes showed increased motility comparted KO, suggesting a defect in actin dynamics. Cultured FcRn KO podocytes also demonstrated abnormal stress fibers compared with WT and the defect could be rescued by IL-6 treatment. This study shows that in podocytes, FcRn modulates the IL-6 mediated response to proinflammatory stimuli and regulates podocytes actin structure, motility and synaptopodin expression.

<b><i>Introduction:</i></b> <i>Opisthorchis viverrini</i> (OV) is a major cause of infection in Southeast Asia. Previous studies in mouse models have shown that OV infection can contribute to immune-complex glomerulonephritis (GN). However, OV infection in human kidney tissue has never been demonstrated. Herein, we evaluated the association of OV infection with biopsy-proven glomerular disease. <b><i>Methods:</i></b> This study was performed in adult patients who underwent kidney biopsy between July 2016 and February 2017. All kidney tissue samples were processed using the standard techniques for renal pathological diagnoses and immunohistochemistry techniques to detect OV antigen. Pre-implanted donor kidney tissue samples were used as controls. The participants were also assessed for OV infection by serum OV immunoglobulin G antibody (Ab) levels and/or presence of OV eggs in stool. <b><i>Results:</i></b> Forty-three renal tissue samples from glomerular disease patients and 50 from transplant donors were included in the study. Mean age in the GN group was 41.7 ± 15.9 years, estimated glomerular filtration rate (eGFR) was 70.65 ± 36.61 mL/min/1.73 m², and median proteinuria was 3.17 (1.70–4.95) g/day. Lupus nephritis (LN) was the most common diagnosis (32.6%), followed by IgA nephropathy (23.3%), IgM nephropathy (18.6%), and primary membranous nephropathy (MN; 7%). The OV antigen was observed in kidney tissue from patients with IgA nephropathy, LN, primary MN, focal segmental glomerulosclerosis, and IgM nephropathy. By contrast, no OV antigen was detected in tissue samples from the control group. The presence of OV antigens was observed in glomerular endothelial cells, mesangial cells, tubular cells, and peritubular capillaries. The odds ratio of positive serum OV Ab to predict the presence of OV antigen in kidney tissues was 4.47 (<i>p</i> = 0.057), and there was a negative correlation between levels of serum OV Ab and eGFR (<i>r</i> = −0.31, <i>p</i> = 0.04). <b><i>Discussion/Conclusion:</i></b> This is the first study to demonstrate the presence of OV antigen in human kidney tissue, which indicates that OV infection may be associated with biopsy-proven glomerular diseases.

Proteinuria is strongly associated with kidney disease progression but the mechanisms underlying podocyte handling of serum proteins such as albumin and IgG remain to be elucidated. We have previously shown that albumin and IgG are transcytosed by podocytes in vitro. In other epithelial cells, the neonatal Fc receptor (FcRn) is required to salvage albumin and IgG from the degradative pathway thereby allowing these proteins to be transcytosed or recycled.Here we directly examine the role of FcRn in albumin and IgG trafficking in podocytes by studying handling of these proteins in FcRn knockout (KO) podocytes in vitro and in a podocytespecific FcRn knockout mice in vivo. In vitro, we find that knockout of FcRn leads to IgG accumulation in podocytes but does not alter albumin trafficking. Similarly, in vivo, podocytespecific knockout of FcRn does not result in albumin accumulation in podocytes in vivo as measured by mean albumin fluorescence intensity whereas these mice demonstrate significant intraglomerular accumulation of IgG over time. In addition we find that podocyte-specific FcRn KO mice demonstrate mesangial expansion as they age and activation of mesangial cells as demonstrated by increased expression of α-smooth muscle actin. Taken together, these results suggest that trafficking pathways for albumin and IgG differ in podocytes and that sustained disruption of trafficking of plasma proteins alters glomerular structure.

Podocytes have been proposed to be antigen presenting cells (APCs). In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against glomerulonephritis. Since podocytes express FcRn, we sought to determine whether the absence of podocyte FcRn ameliorates immune-mediated disease. We examined MHCII and costimulatory markers expression in cultured wild type (WT) and FcRn knockout (KO) podocytes. Interferon gamma (IFNγ) induced MHCII expression in both WT and KO podocytes but did not change CD80 expression. Neither WT nor KO expressed CD86 or inducible costimulatory ligand (ICOSL) at baseline or with IFNγ. Using an antigen presentation assay, WT podocytes but not KO treated with immune complexes induced a modest increase in IL-2. Induction of the anti-glomerular basement membrane (anti-GBM) model resulted in a significant decrease in glomerular crescents in podocyte-specific FcRn knockout mouse (podFcRn KO) versus controls but the overall percentage of crescents was low. To examine the effects of the podocyte-specific FcRn knockout in a model with a longer autologous phase, we used the nephrotoxic serum nephritis (NTS) model. We found that the podFcRn KO mice had significantly reduced crescent formation and glomerulosclerosis compared to control mice. This study demonstrates that lack of podocyte FcRn is protective in immune mediated kidney disease that is dependent on an autologous phase. This study also highlights the difference between the anti-GBM model and NTS model of disease.

Background Lupus nephritis is a type of major organ involvement in systemic lupus erythematosus (SLE) patients that leads to higher rates of morbidity and mortality and may present initially in 28% of SLE patients. However, there are limited data available on clinical differences or predictors for biopsy-proven lupus nephritis in established versus newly diagnosed SLE cases. Methods Adult patients undergoing kidney biopsy for the first time with a diagnosis of lupus nephritis were eligible for inclusion. Patients were categorized into two groups: those with previously diagnosed SLE and those with newly diagnosed SLE by kidney biopsy. Factors associated with newly diagnosed SLE were determined using logistic regression analysis. Results There were 68 patients diagnosed with lupus nephritis by kidney biopsy. Of those, 31 cases (45.58%) were newly diagnosed. The newly diagnosed SLE group was significantly older (36.87 vs 30.95 years) and had a lower proportion of females (74.19% vs 91.89%) than the previously diagnosed group. A new-onset hypertension was the only factor independently associated with newly diagnosed SLE by kidney biopsy. The adjusted odds ratio (95% CI) was 5.152 (1.046, 25.363). Conclusions Nearly half of the biopsy-proven lupus nephritis cases in this study were patients with newly diagnosed SLE. Patients with previously diagnosed SLE and newly diagnosed SLE by kidney biopsy had clinical differences.