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.