Transient maintenance of tracheal patency upon the insertion of a flexible bronchoscope in a patient with an anterior mediastinal mass: a case report.

BACKGROUND: Patients with an anterior mediastinal mass are at risk of perioperative respiratory collapse. CASE PRESENTATION: A 74-year-old woman with a large anterior mediastinal mass that led to partial tracheal collapse (shortest diameter, 1.3 mm) was scheduled for tracheobronchial balloon dilation and stent placement under general anesthesia. Although veno-venous extracorporeal membrane oxygenation (V-V ECMO) had been established, maximum flow was limited to 1.6 L/min, and general anesthesia induction was followed by hypoxia probably due to inadequate ventilation. A flexible bronchoscope was inserted through the tracheal lumen that was being compressed by the anterior mass; this not only increased tracheal patency but also enabled positive pressure ventilation and resulted in recovery from hypoxia. Scheduled procedures were successfully performed without complications. CONCLUSION: We describe a case wherein tracheal patency was transiently maintained by inserting a flexible bronchoscope in a patient with an anterior mediastinal mass.

[Clinico-histopathological analysis of renal changes in MPO-ANCA-associated vasculitis].

OBJECTIVE: The pathological and clinical findings, therapies and prognoses of MPO-ANCA-associated vasculitis, were investigated in cases who showed rapidly progressive nephritic syndrome and received renal biopsy. METHODS: Vasculitis activity was evaluated by BVAS(Birmingham Vasculitis Activity Score). The renal biopsy findings were evaluated by scoring glomeruli, interstitial and vascular lesions. The renal prognoses were studied by dividing the cases into a dialysis group, which went onto maintenance dialysis in one year and another group without dialysis, which maintained renal functions. RESULTS: The average age was 58.6 +/- 13.9 years, and the 60s age bracket was the largest. Vasculitis activity was 14.8 +/- 3.2 on the average by BVAS. CRP was 1.2 +/- 1.4 for the kidney-located type group, and 12.6 +/- 10.5 for the multiorgan-damaged group respectively, which shows the former to be significantly lower (p = 0.0079). Serum creatinine at renal biopsy was 3.57 +/- 2.31 mg/dL in the dialysis-independent group, and this was significantly lower than the serum creatinine level of 9.10 +/- 2.6 mg/dL of the dialysis group (p = 0.000259). As for the renal pathological findings, the percentage of global sclerosis among all the glomeruli was 24.7 +/- 19.9% in the dialysis-independent group vs. 68.5 +/- 19.7% in the dialysis group, which shows the latter to be significantly higher (p = 0.002). CONCLUSION: CRP was significantly higher in the multi-organ-damaged group relative to the kidney-located type group. The percentage of global sclerosis determined by renal biopsy and the amount of serum creatinine at the renal biopsy were key factors in determining the renal prognosis. The absence of a significant correlation between the percentage of crescentic formation and the renal prognosis suggests the possibility of suppressing progress to global sclerosis.

Risk factors for progression in patients with early-stage chronic kidney disease in the Japanese population.

OBJECTIVE: Chronic kidney disease (CKD) is an important worldwide health problem. The incidence of end-stage renal disease (ESRD) is increasing steadily around the world, however few studies have discussed the risk factors for progression in patients with early-stage CKD. Therefore, we designed a retrospective cohort study of patients with early-stage CKD to identify the risk factors influencing the annualized slope of the estimated glomerular filtration rate (eGFR). METHODS AND PATIENTS: In this longitudinal cohort study, baseline examination was conducted in 2012 outpatients treated at the Kidney Center, Tokyo Women's Medical University. Follow-up examinations were completed in 485 patients with stage 1 and stage 2 CKD within the study period (2002-2007). The conventional risk factors for CKD progression, such as proteinuria, blood pressure, serum triglyceride, serum HDL, fasting plasma glucose, smoking habit, hypertension or treatment with antihypertensive medication and body mass index, were examined. The annualized eGFR slope was calculated at the start and end of the study period. Multivariate analysis was performed to determine the associations of the eGFR slope with the predisposing risk factors. RESULTS: The mean annualized eGFR slope was -1.64 mL/min/1.73 m(2)/year. Concerning the relationship between etiology and the GFR decreasing slope, IgA nephropathy was defined as the worst (-1.80 mL/min/year) due to the high ratio of proteinuria. Proteinuria (-2.13 mL/min/1.73 m(2)/year, p=0.005), smoking habit (-2.06 mL/min/1.73 m(2)/year, p=0.014), low serum HDL (-1.95 mL/min/1.73 m(2)/year, p=0.035), and hypertension (-1.73 mL/min/1.73 m(2)/year, p=0.045) were all significantly related to the eGFR slope. The estimated GFR for the highest BMI quartile was significantly higher than that of the eGFR for the lowest BMI. CONCLUSION: Proteinuria, smoking habit, hypertension and low HDL were clearly related to accelerated disease progression in patients with early-stage CKD. Therefore, aggressive treatment of these risk factors is essential in the early stages of CKD.

[Effects of steroid therapy on membranous nephropathy].

BACKGROUND: Although membranous nephropathy is a common cause of nephrotic syndrome in adults, its treatment remains under debate. METHODS: To clarify the effects of steroid therapy, the data of 51 Japanese adult patients with idiopathic membranous nephropathy who received treatment at our department were analyzed retrospectively. We divided the patients with nephrotic syndrome and a serum creatinine level <1.7 mg/dL, into two groups: the steroid therapy group (n=20) and the non-steroid therapy group (n=7), and compared the clinical characteristics between the two groups. RESULTS: Significantly decreased proteinuria levels (p<0.05) after 2 and 5 years were observed in the steroid therapy group as compared to the non-steroid therapy group. There was no significant difference in the serum creatinine levels after 2 and 5 years between the steroid therapy group and the non-steroid therapy group. CONCLUSION: Steroid therapy in idiopathic membranous nephropathy showed good efficacy in patients with nephrotic syndrome.

ATF3 protects against renal ischemia-reperfusion injury.

Oxidative stress-induced cell death plays a major role in the progression of ischemic acute renal failure. Using microarrays, we sought to identify a stress-induced gene that may be a therapeutic candidate. Human proximal tubule (HK2) cells were treated with hydrogen peroxide (H2O2) and RNA was applied to an Affymetrix gene chip. Five genes were markedly induced in a parallel time-dependent manner by cluster analysis, including activating transcription factor 3 (ATF3), p21(WAF1/CiP1) (p21), CHOP/GADD153, dual-specificity protein phosphatase, and heme oxygenase-1. H2O2 rapidly induced ATF3 approximately 12-fold in HK2 cells and approximately 6.5-fold in a mouse model of renal ischemia-reperfusion injury. Adenovirus-mediated expression of ATF3 protected HK2 cells against H2O2-induced cell death, and this was associated with a decrease of p53 mRNA and an increase of p21 mRNA. Moreover, when ATF3 was overexpressed in mice via adenovirus-mediated gene transfer, ischemia-reperfusion injury was reduced. In conclusion, ATF3 plays a protective role in renal ischemia-reperfusion injury and the mechanism of the protection may involve suppression of p53 and induction of p21.

The characteristics of relapse in adult-onset minimal-change nephrotic syndrome.

BACKGROUND: Although minimal-change nephrotic syndrome (MCNS) is highly steroid-responsive, the frequency of relapses in some patients is high, necessitating the administration of repeated courses of prednisolone in high doses. It is, therefore, necessary to identify factors that can predict this increased risk of relapse in some patients in order to establish useful treatment methods to reduce the risk. METHODS: To clarify the factors that might increase the risk of relapses, the data of 82 Japanese adult patients with MCNS receiving treatment at our department were analyzed retrospectively. Of the total, 55 patients (67.1%) experienced relapse after showing an initial response. We divided the patients into two groups; namely, the nonrelapse group (n = 27) and the relapse group (n = 55), and compared the clinico-pathophysiological characteristics between the two groups. RESULTS: Significantly increased serum immunoglobulin E (IgE) levels (P = 0.0002) and increased frequency of steroid side effects were observed in the relapse group as compared to the nonrelapse group. CONCLUSIONS: To develop effective therapeutic modalities, it is important to have a thorough understanding of the clinico-pathophysiological characteristics of MCNS patients showing relapse.

Protective effect of carbon monoxide donor compounds in endotoxin-induced acute renal failure.

BACKGROUND: Sepsis is a common cause of acute renal failure (ARF) in clinical practice. However, the precise mechanism of endotoxin-induced ARF is not fully understood. There have been several reports that inhalation of carbon monoxide (CO) gas could be protective against acute rejection in intestine, lung, and kidney transplantation. Thus, we investigated the direct effect of CO in an experimental ARF model of septic shock induced by lipopolysaccharide (LPS). METHOD: Mice were pretreated with [Ru(CO)3Cl2]2 (CO donor compounds) at various concentrations (0.5, 1.0 and 2.0 microg) which were intravenously injected 24 h before intraperitoneal LPS injection. Biomarkers including myeloperoxidase activity and histochemical staining were evaluated. RESULTS: The elevation of plasma creatinine was suppressed in CO donor-pretreated mice compared with vehicle-treated mice (creatinine 0.35 vs. 0.25; p < 0.05) 24 h after LPS injection. Renal myeloperoxidase activity slightly decreased in CO donor-pretreated mice. In the histological examination, neutrophil infiltration was significantly diminished in CO donor-treated mice. Real-time polymerase chain reaction revealed significant improvements in inflammatory related genes, such as TNFalpha, MCP-1, RANTES and IL4. CONCLUSION: Our results suggest the protective effect of the CO donor against endotoxin-induced renal injury; however, further study is needed to elucidate the mechanism.

Klotho reduces apoptosis in experimental ischaemic acute renal failure.

BACKGROUND: Klotho is associated with the suppression of several ageing phenotypes. Because high klotho gene expression was detected in the kidney and several studies have found altered expression in animal models, we explored the physiological relevance of klotho expression in the kidney under renal ischemia reperfusion injury (IRI). METHODS: Male Wistar rats were subjected to bilateral renal ischemia or sham operation, followed by reperfusion for 6, 12 or 24 h, or 2 to 10 days. Renal expression of klotho was assessed by real-time PCR or Western blotting. Creatinine levels were determined. Immunohistochemical studies and TUNEL staining were performed. An adenovirus harbouring the mouse klotho gene (ad-kl) was intravenously administered to one group of rats before renal IRI. RESULTS: Renal klotho mRNA and protein expressions were significantly reduced in IRI rats the first day after ischemia. Pre-treatment with ad-kl resulted in a robust induction of klotho mRNA and protein in the liver but not in the kidney. Ad-kl gene transfer improved serum creatinine and the histological changes. Apoptosis induced by IRI was attenuated following ad-kl administration. CONCLUSION: The data suggest klotho to be involved in the pathophysiology of IRI. Downregulation of renal klotho exacerbates ischaemic acute renal failure, and klotho gene induction has therapeutic potential in managing ischaemic renal damage.

CD2AP expression in a renal ischemia/reperfusion injury model and analysis of its related genes using overexpression and RNA interference technique.

BACKGROUND: CD2-associated protein (CD2AP) is a ubiquitously expressed 80-kDa intracellular protein, and has been speculated to act as an intracellular signaling pathway between plasma membrane proteins and cytoskeleton proteins. CD2AP expression has been reported in both the glomerulus and tubular epithelium in the kidney, and CD2AP knockout mice exhibit congenital nephrotic syndrome. However, the precise properties and its role in the renal tubules have not been clarified. METHODS: We used an established rat model of ischemic/reperfusion renal injury (IRI) to examine the expression of CD2AP by real-time PCR, Western blotting, and immunohistochemistry. We also investigated the expression of genes related to apoptosis and cell proliferation in mouse collecting duct-derived cells (M1 cells) transfected with full-length of CD2AP cDNA or short interfering RNA. RESULTS: CD2AP mRNA and protein expression had significantly increased in the IRI kidney. Real-time PCR indicated that expression of genes regulating apoptosis, such as B-Raf and Caspase-12, and genes regulating cell proliferation factors, CDC2, was decreased in CD2AP-overexpressing M1 cells and increased in CD2AP-interfered M1 cells. CONCLUSIONS: These results suggest that CD2AP expression was increased following renal ischemia and that CD2AP may be related to the process of cell repair and/or cell differentiation following injury.

Oxidative stress decreases klotho expression in a mouse kidney cell line.

BACKGROUND/AIMS: Defects in klotho gene expression in the mouse result in a syndrome that resembles human aging. We recently identified expression of klotho in a mouse inner medullary collecting duct (mIMCD3) cell line for the first time, and in the present study we explored the physiological relevance of the regulation of klotho expression in the presence of oxidant stress injury. METHODS: Klotho expression was analyzed by real-time PCR, Western blot, and immuocytochemical staining during exposure to hydrogen peroxide (H2O2). Overexpression of the klotho gene was induced by klotho adenoviruses, and the number of apoptotic cells was counted by flowcytometry. RESULTS: Oxidant stress injury by H2O2 dose-dependently reduced klotho expression and diminished klotho staining. There were fewer apoptotic cells among the klotho-transfected cells than among the control cells. CONCLUSION: Klotho is expressed in cell line mIMCD3, and the klotho gene may be involved in the process of oxidative stress injury and apoptosis in this cell line.

[Functional analysis of the left-right determinant inv (inversion of embryonic turning) gene].

We identified the inv gene that encodes left and right asymmetry and regulates kidney development based on the information of the inv mutant mouse. However, functional properties and the modulator of gene expression of inv have been unclear. We used the tissue injury model for assessing the functional roles of inv in ischemia reperfusion injury (IRI). The kidney tissue taken from rats with IRI showed reciprocal changes in mRNA expression of inv: a 0.25-fold decrease at 6 hours and then a gradual increase to a maximum 1.8-fold rise at 10 days of reperfusion. Next, oxidative stress was induced by exposing mouse inner medullary collecting duct (mIMCD-3) cells to hydrogen peroxide(H2O2) in the medium. Real-time PCR showed that mRNA expression of inv decreased 0.52-fold at 3 hours with 0.2 mM H2O2 in the medium, and then increased 3.1-fold at 24 hours with 0.1 mM H2O2 in the medium. RNA interference (RNAi) is a powerful tool to inhibit gene expression in experimental model systems. We knocked down inv gene expression in mIMCD-3 cells using RNAi to investigate the function of the inv gene. We designed a small interfering RNA (siRNA) to target the coding region of inv (inv-siRNA) and random-sequence scrambled siRNA(control siRNA). mIMCD-3 cells transfected with either the inv-siRNA or control siRNA were observed by microscopy. The cells transfected with inv-siRNA progressively lost cell-to-cell contact and the cell population significantly diminished approximately 48 hours post-transfection. The changes in gene expression profile were observed at time points (36 hours) using real-time PCR-based gene screening with categorized primer sets. Several genes related to structural protein of the matrix were downregulated. In contrast, repairing related genes were upregulated. In conclusion, gene expression of inv was modulated under oxidative stress and the inv gene may play a role in repairing and regenerating renal epithelial cells.

Osmoadaptation-related genes in inner medulla of mouse kidney using microarray.

To distinguish biological molecular processes of osmotic stress occurring in inner medulla, we utilized microarrays to monitor expression profiles. RNAs from three segments (cortex, outer medulla, and inner medulla) of mouse kidney were isolated and applied to microarrays. We found 35 genes expressed highly in inner medulla. Next, microarrays for the RNAs from mouse medullary collecting duct cell line (mIMCD) cells and osmotically adapted mIMCD cells (HT cells) were performed (designed as resistant to 1270mOsm/H(2)O). Of 35 genes highly expressed in inner medulla, 6 genes such as; B-cell translocation gene protein (BTG), myc-basic motif homologue, gelsolin, cell surface glycoprotein, laminin beta2, and tubulo-interstitial nephritis antigen, were also expressed highly in HT cells. Using real-time PCR, we confirmed the expression of six genes. Additionally acute osmotic stress induced the BTG. By comparing the inner medulla to a mIMCD3, we identified genes which respond to acute and chronic hyperosmotic stress.

Retroperitoneal fibrosis associated with membranous nephropathy effectively treated with steroids.

Corticosteroids were successfully used to treat a 66-year-old man with retroperitoneal fibrosis (RPF) and previously diagnosed membranous nephropathy. Proteinuria was noted at the age of 51 years, and membranous nephropathy was diagnosed by renal biopsy. Ten years later, he presented with right hydronephrosis and renal dysfunction, and was diagnosed as having RPF based on the typical diagnostic imaging findings. Steroid therapy was successful, resulting in improvement of the hydronephrosis and renal function. The hydronephrosis recurred three years later, but corticosteroids were again effective in improving ureteral obstruction. This was a rare case of recurrent RPF with membranous nephropathy in which steroid therapy was effective in treating pleural effusion and hypergammaglobulinemia during the clinical course. This case suggests that an immunological disorder is involved in the pathogenesis of RPF.