Pleuroperitoneal Communication and Ovarian Cancer Complicating Peritoneal Dialysis: A Case Report of a Patient with End-Stage Kidney Disease.

Peritoneal dialysis has been a widely accepted modality for treating end-stage kidney disease, but a regular dialysis schedule can be seriously disrupted by various comorbid conditions requiring surgical intervention. A 40-year-old woman who had been receiving peritoneal dialysis was sequentially but separately complicated by pleuroperitoneal communication and ovarian cancer. Despite the need for temporary interruption of her peritoneal dialysis schedule, it was successfully resumed after the relevant surgeries for each disease. Several concerns regarding overall postoperative dialytic management strategies, including how to deal with the peritoneal dialysis catheter during the postoperative period as well as how long peritoneal dialysis should be interrupted, which remain an unresolved issue in the field of nephrology, are also discussed.

Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue.

Because of their mechanical strength, chemical stability, and low molecular weight, carbon nanotubes (CNTs) are attractive biological implant materials. Biomaterials are typically implanted into subcutaneous tissue or bone; however, the long-term biopersistence of CNTs in these tissues is unknown. Here, tangled oxidized multi-walled CNTs (t-ox-MWCNTs) were implanted into rat subcutaneous tissues and structural changes in the t-ox-MWCNTs located inside and outside of macrophages were studied for 2 years post-implantation. The majority of the large agglomerates were present in the intercellular space, maintained a layered structure, and did not undergo degradation. By contrast, small agglomerates were found inside macrophages, where they were gradually degraded in lysosomes. None of the rats displayed symptoms of cancer or severe inflammatory reactions such as necrosis. These results indicate that t-ox-MWCNTs have high biopersistence and do not evoke adverse events in rat subcutaneous tissue in vivo, demonstrating their potential utility as implantable biomaterials.

The interaction of LFA-1 on mononuclear cells and ICAM-1 on tubular epithelial cells accelerates TGF-ß1-induced renal epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) of renal epithelial cells (RTECs) has pivotal roles in the development of renal fibrosis. Although the interaction of lymphocyte function-associated antigen 1 (LFA-1) on leukocytes and its ligand, intracellular adhesion molecule 1 (ICAM-1), plays essential roles in most inflammatory reactions, its pathogenetic role in the EMT of RTECs remains to be clarified. In the present study, we investigated the effect of the interaction of LFA-1 on peripheral blood mononuclear cells (PBMCs) and ICAM-1 on HK-2 cells after stimulation with TGF-ß(1) on the EMT of RTECs. ICAM-1 was highly expressed in HK-2 cells. After TGF-ß(1) stimulation, the chemokines CCL3 and CXCL12 increased on HK-2 cells. After co-culture of PBMCs and HK-2 cells pre-stimulated with TGF-ß(1) (0.1 ng/ml) (HK-2-TGF-ß(1) (0.1)), the expression of the active form of LFA-1 increased on PBMCs; however, total LFA-1 expression did not change. The expression of the active form of LFA-1 on PBMCs did not increase after co-culture with not CCL3 but CXCL12 knockdown HK-2-TGF-ß(1) (0.1). The expression of epithelial cell junction markers (E-cadherin and occludin) further decreased and that of mesenchymal markers (vimentin and fibronectin) further increased in HK-2-TGF-ß(1) (0.1) after co-culture with PBMCs for 24 hrs (HK-2-TGF-ß(1) (0.1)-PBMCs). The phosphorylation of ERK 1/2 but not smad2 and smad3 increased in HK-2-TGF-ß(1) (0.1)-PBMCs. The snail and slug signaling did not increase HK-2-TGF-ß(1) (0.1)-PBMCs. Although the migration and invasion of HK-2 cells induced full EMT by a high dose (10.0 ng/ml) and long-term (72-96 hrs) TGF-ß(1) stimulation increased, that of HK-2-TGF-ß(1) (0.1)-PBMCs did not increase. These results suggested that HK-2 cells stimulated with TGF-ß(1) induced conformational activation of LFA-1 on PBMCs by increased CXCL12. Then, the direct interaction of LFA-1 on PBMCs and ICAM-1 on HK-2 cells activated ERK1/2 signaling to accelerate the part of EMT of HK-2 cells induced by TGF-ß(1).

A case of cervical cancer-related membranous nephropathy treated with radiation therapy.

Paraneoplastic nephropathy is a rare complication of malignant disease. We present a case of cervical cancer with biopsy-proven membranous nephropathy and associated nephrotic syndrome. Irradiation to the specific neoplasm site and to the metastatic paraaortic lymph node tissues lead to regression of the nephrotic syndrome without causing severe adverse events. Radiation therapy can be the first choice in the treatment of paraneoplastic nephrotic syndrome if the primary neoplasm is unresectable. Invasiveness of intervention and patient prognosis should be carefully deliberated in the management of the two diseases.

Development of a technique for introduction of an expressed complementary deoxyribonucleic acid into parathyroid cells by direct injection.

PTH is a major mediator of bone and mineral metabolism. However, physiological and pathological investigations of parathyroid cells (PTCs) have been limited because of the lack of available cell lines and because the organ is too small for detailed studies. Here, we describe a novel method for adenovirus-mediated cDNA transfer into PTCs, and we show the accuracy of the method in a rat model of uremia-induced secondary hyperparathyroidism. Rats underwent a 5/6-nephrectomy and were fed with a high-phosphate diet for 8 wk. The parathyroid glands were surgically exposed and adenoviruses containing LacZ or Ca-sensing receptor (CaSR) were directly injected into the glands under a zoom-stereo microscope. The parathyroid glands were analyzed for infection of adenovirus and immunohistochemically for expression of CaSR. The functional activity of exogenous CaSR in PTCs after this treatment was investigated based on changes of the calcium and PTH curve. A virus concentration of more than 10(9) plaque-forming units/ml was required for adequate infection of PTCs within 7 d after treatment. Marked increase of CaSR-positive PTCs by 2.39 +/- 0.72 times relative to control treatment, and significant colocalization of CaSR overexpression and virus labeling, were observed in glands after gene introduction. The calcium and PTH curve was shifted to the left from the basal position (set point, 1.10 +/- 0.09 to 0.76 +/- 0.12 mm; P < 0.0001), indicating successful introduction of a functionally active cDNA into the PTCs. This technique may facilitate an elucidation of biological effects through targeting and identification of specific features of PTCs, which may provide the basis for new clinical approaches.

[Case of lupus nephritis and enteritis associated with bilateral hydronephrosis].

A case of nephrotic syndrome associated with bilateral hydronephrosis in a 26-year-old female is reported. She was referred to our hospital because of persistent diarrhea, abdominal pain, and urinary disorders. On admission, ascites, intestinal edema, and bilateral hydronephrosis, were demonstrated by radiographic analysis. The findings of both physical and laboratory examinations showed evidence of systemic lupus erythematosus (SLE). In addition, diffuse proliferative lupus nephritis was consistently confirmed by a renal biopsy. Immediately after the initiation of steroid treatment, her abdominal symptoms disappeared followed by an improvement in the symptoms of intestinal edema, hydronephrosis, and the renal function. The relationship between ureterohydronephrosis and lupus cystitis, and the fact that lupus enteritis is often associated with lupus cystitis have been demonstrated by previous studies. Finally, the clinical manifestations observed in our case led us to consider the association of lupus enteritis and cystitis. We should bear in mind the possible association of several disorders, including nephrotic syndrome, enteritis, and hydronephrosis due to cystitis, in cases presenting with SLE.

[Nephrotic syndrome associated with lung adenocarcinoma: report of an autopsy case].

A 73-year-old male with nephrotic syndrome was admitted to our hospital. He was empirically treated with prednisolone, which resulted in the alleviation of proteinuria, hypoproteinemia, and pleural effusion. Thereafter, a computed tomographic scan revealed a mass lesion in the right-lower lung field. Finally, the patient died of multiple organ failure induced by disseminated intravascular coagulation. Adenocarcinoma of the lung and membranous nephropathy (MN) were revealed by autopsy. MN tends to occur in the elderly, and is also occasionally associated with solid tumors, such as lung and gastrointestinal cancer. Therefore, a malignancy survey may be useful in the management of cases with nephrotic syndrome in which MN is pathologically defined. However, the initiation of empirical treatment without a pathological diagnosis is not an exceptional phenomenon. Physicians should, therefore, bear in mind the potential association of malignancy and immediately and carefully investigate the potential presence of a malignancy in elderly patients with a new onset of nephrotic syndrome.

[Case of Henoch-Schönlein purpura nephritis associated with IgA monoclonal gammopathy of undetermined significance].

We report the case of a 72-year-old man with nephritic syndrome and rapidly progressive renal failure due to Henoch-Schönlein purpura nephritis (HSPN). He was successfully treated with methylprednisolone pulse therapy, followed by oral prednisolone at the dose of 30 mg per day. He was also diagnosed by immunoelectrophoresis as IgA-lambda monoclonal gammopathy of undetermined significance (IgA-MGUS). Renal biopsy revealed the diffuse crescentic glomerulonephritis associated with mesangial deposition of IgA and C3. Since an immunofluorescence examination failed to show the deposition of lambda, the significance of IgA paraproteinemia on the HSPN was obscure in the present case. However, we must bear in mind the latent presence of IgA-MGUS in cases of HSPN.

Molecular and morphological approach of uremia-induced hyperplastic parathyroid gland following direct maxacalcitol injection.

The mechanisms explaining the clinical effects of direct maxacalcitol (OCT) injection into the hyperplastic parathyroid gland (PTG) in uremic patients with advanced secondary hyperparathyroidism (SHPT) were investigated by molecular and morphological examination. PTG of uremia-induced SHPT model rats were treated by a direct injection of OCT (DI-OCT) or vehicle (DI-vehicle). The changes in serum intact parathyroid hormone (intact-PTH) level, vitamin D and Ca-sensing receptor (VDR and CaSR, respectively) expression levels in PTG, and the calcium (Ca)-PTH response curve were examined; the induction of apoptosis in parathyroid cells (PTC) was also analyzed by the TUNEL method, DNA electrophoresis, and electron microscopic examination. Serum intact-PTH level following DI-OCT significantly decreased. Upregulation of both VDR and CaSR, a clear shift to the left downward in the Ca-PTH curve, and many apoptotic PTCs were observed in the DI-OCT-treated PTGs. However, these findings were not observed in the DI-vehicle-treated PTGs. Moreover, these effects were confirmed by the DI-OCT into one PTG and DI-vehicle alone into another PTG in the same rat. DI-OCT may introduce simultaneous VDR and CaSR upregulation and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH level in uremia-induced advanced SHPT.

Spironolactone suppresses peritubular capillary loss and prevents deoxycorticosterone acetate/salt-induced tubulointerstitial fibrosis.

We examined whether and how peritubular capillary (PTC) loss in the renal cortex contributes to the development of deoxycorticosterone acetate (DOCA)/salt-induced tubulointerstitial fibrosis. Uninephrectomized rats provided with 0.9% NaCl/0.3% KCl drinking solution ad libitum were divided into control, DOCA, and spironolactone groups, which were administered vehicle, DOCA alone, and DOCA plus spironolactone for 1 (initial phase) and 4 weeks (delayed phase), respectively. Exposure to DOCA initiated a sequence of events that initially involved reduced PTC density, followed by a delayed response that involved further reduced PTC density, development of tubulointerstitial fibrosis and hypertension, enhanced expression of transforming growth factor-beta1 and connective tissue growth factor, and impaired renal function. Concomitant with the reduced PTC density, the 2 hypoxia-responsive angiogenic factors (vascular endothelial growth factor and hypoxia-inducible factor-1alpha) and the antiangiogenic factor (thrombospondin-1) were upregulated in cortical tubular cells of the DOCA group during the 2 phases and only in the delayed phase, respectively. In the DOCA group, PTC endothelial cell apoptosis was enhanced during the 2 phases, and PTC endothelial cell proliferation was inhibited in the delayed phase. In accordance with upregulation of thrombospondin-1, p53 expression was enhanced in the DOCA group in the delayed phase. The initial and delayed effects of DOCA were blocked in the spironolactone group. We conclude that exposure to DOCA initially caused the reduced PTC density associated with enhanced apoptosis independent of thrombospondin-1, which induced tubulointerstitial fibrosis via p53-mediated thrombospondin-1 activation, and spironolactone conversely corrected the effects of DOCA to prevent fibrosis.

[Case of Henoch-Schönlein purpura nephritis complicated with essential mixed cryoglobulinemia].

We report a case of purpura nephritis complicated with essential mixed cryoglobulinemia. The patient was referred to our hospital because of a petechial rash on the lower extremities, microscopic hematuria, and progressive deterioration of renal function. The presumptive diagnosis of Henoch-Schönlein purpura (HSP) was made, and the patient was treated with prednisolone at the dose of 40 mg/day. However, there was a persistent purpuric skin rash. On the other hand, immunoelectrophoresis of the serum revealed the presence of IgA-lambda and polyclonal IgG in the cryoprecipitate. Granular staining for polyclonal rather than monoclonal IgA and C3 segmentally along the capillary walls demonstrated by immunofluorescence analysis of renal biopsy led to the diagnosis of purpura nephritis as the major mechanism of renal damage. After three sessions of cryofiltration, the patient's serum cryoglobulins decreased and the active rash finally settled, along with improvement of renal function. These observations suggest that the presence of cryoglobulinemia modulated the clinical course of HSP in our case. Therefore, the possibility of the latent presence of cryoglobulinemia in cases with HSP having an active rash refractory to steroid treatment should not be overlooked.