Takahiko Ogawa

Immunohistochemical Studies of Vitronectin, C5b-9, and Vitronectin Receptor in Membranous Nephropathy

To investigate the involvement of vitronectin, the terminal complement complex (C5b-9), and the vitronectin receptor in the pathogenesis of membranous nephropathy, the immunohistochemical localization of these antigens in the kidney was determined using the immunoperoxidase method and monoclonal antibodies: antivitronectin, anti-SC5b-9 (neoantigen), and antivitronectin receptor (specific for alpha v beta 3 and alpha v). The subjects were 6 patients with membranous nephropathy, and the controls were 2 patients with minimal-change nephrotic syndrome. In membranous nephropathy, vitronectin was localized in subepithelial deposits and in epithelial cell foot processes and was intensely positive in the foot processes adjacent to subepithelial deposits. C5b-9 showed a similar pattern of localization to vitronectin. Both alpha v beta 3 and alpha v were localized in the basal portions of the foot processes of visceral epithelial cells as well as along the borders of these cells adjacent to the urinary space. Deposition at the former site was heavier than at the latter, and localization was especially prominent adjacent to the subepithelial deposits. In addition, alpha v was localized around and within some of the electron-lucent subepithelial deposits in the basement membrane. In contrast, the deposition of vitronectin, C5b-9, alpha v beta 3, and alpha v was always less intense in minimal-change nephrotic syndrome than in membranous nephropathy. Vitronectin and C5b-9 were localized to small parts of mesangium and glomerular basement membrane, while alpha v beta 3 and alpha v deposits showed no difference in intensity between the basal portions of the foot processes and the urinary border of the visceral epithelial cells. Thus, membranous nephropathy featured increased localization of vitronectin, C5b-9, and vitronectin receptors both within and around the subepithelial deposits, suggesting that the mechanism of immune complex disposal via the vitronectin receptor and the vitronectin-C5b-9 complex, associated with complement activation due to subepithelial immune complex formation, may also be active.

Precise ultrastructural localization of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in patients with IgA nephropathy

Using light and electron microscopy, we performed an immunohistochemical study of endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in 15 patients with IgA nephropathy to clarify the localization of these adhesion molecules. The normal portions of 2 kidneys removed due to localized carcinoma and 3 biopsies from patients without glomerular disease were used as a control. By light microscopy, ELAM-1, VCAM-1, and ICAM-1 all showed positive staining in IgA nephropathy, with the intensity of staining following the sequence ICAM-1 > VCAM-1 > ELAM-1. ELAM-1 and VCAM-1 showed a patchy distribution of moderate staining in the tissues, including the mesangium, crescents, adhesions, and tubules. In contrast, there was marked linear ICAM-1 staining throughout the vascular walls. ELAM-1 and VCAM-1 were positive on the basolateral surfaces of a few proximal tubular epithelial cells in association with inflammatory cell infiltration, while ICAM-1 was found on the brush border. ICAM-1 was positive in the glomerular capillary walls and interstitial vessels of the control kidney tissue, while ELAM-1 and VCAM-1 were virtually absent. By electron microscopy, ELAM-1 positivity on the urinary surface of the parietal/visceral epithelial cells was often associated with adherent mononuclear cells in the urinary space. VCAM-1 positivity was increased in the perinuclear space and/or cytoplasm of mesangial cells as well as at the mesangial cell-endothelial cell interface. These findings suggest that ELAM-1 and VCAM-1 may be more closely related than ICAM-1 to the major histopathological changes occurring in IgA nephropathy, including mesangial expansion, formation of crescents and adhesions, and tubulointerstitial injury.

Continuous Ambulatory Peritoneal Dialysis Is Superior to Hemodialysis in Chronic Dialysis Patients with Cerebral Hemorrhage

Continuous Ambulatory Peritoneal Dialysis Is Superior to Hemodialysis in Chronic Dialysis Patients with Cerebral Hemorrhage N. Noriaki Yorioka H. Hiroaki Oda T. Takahiko Ogawa Y. Yoshihiko Taniguchi S. Shigeyuki Kushihata A. Atsuo Takemasa K. Koji Usui K. Kenichiro Shigemoto S. Satoru Harada M. Michio Yamakido 2nd Department of Internal Medicine, Hiroshima University School of Medicine, and Ichiyokai Harada Hospital, Hiroshima, Japan

Localization of Hepatocyte Growth Factor and Tubulointerstitial Lesions in IgA Nephropathy

To investigate the relationship between localization of hepatocyte growth factor (HGF) and tubulointerstitial lesions (TILs) in the cortical area of renal biopsy specimens, a clinicopathological study was performed in 35 patients with IgA nephropathy. HGF was detected by an enzyme-antibody method and TILs were assessed semiquantitatively by light microscopy. HGF was observed mainly on epithelial cells in the tubules, but not in the glomeruli. Fourteen patients had biopsies that were positive for HGF. There was a correlation between HGF positivity and histological damage, the TIL grade, and several clinical parameters determined at biopsy. Thus, HGF is related to TILs in IgA nephropathy, and may be a factor in the exacerbation of this disease.

Ultrastructural localization of vascular cell adhesion molecule-1 in proliferative and crescentic glomerulonephritis

Recent studies have demonstrated an important role of vascular cell adhesion molecule-1 (VCAM-1) in the pathogenesis of nephritis. In the present study, renal biopsy specimens from patients with proliferative and crescentic glomerulonephritis were subjected to immunoelectron microscopy using an anti-VCAM-1 monoclonal antibody. In control normal kidney tissue, VCAM-1 expression was restricted to the free surface of parietal epithelial cells. In diseased glomeruli, VCAM-1 was expressed on the free surface of parietal and visceral epithelial cells, on the luminal surface of capillary endothelial cells, on infiltrating monocyte/macrophage-like cells, on mesangial cells, and in the matrix of the expanded mesangium. There was also VCAM-1 expression on almost all cell types in the crescents, including macrophage-like cells, fibroblast-like cells, and epithelial cells. Some cells also showed VCAM-1 positivity in the rough endoplasmic reticulum and the perinuclear space. Both the glomerular capillary lumen and urinary spaces of Bowmans capsule contained positive reaction products, which were often associated with exocytosis by the surrounding cells. VCAM-1 was predominantly expressed on the basal and lateral surfaces of a few proximal tubules, but it could not be localized ultrastructurally. These findings suggest that production and secretion of VCAM-1 by both infiltrating monocyte/macrophages and resident glomerular cells may be related to the pathogenesis of proliferative and crescentic glomerulonephritis.

Glomerulocystic Kidney Disease in a Young Adult

We report an 18-year old woman who had glomerulocystic kidney disease (GCKD) without a family history of renal disease or hypertension and no known congenital abnormalities. Her renal function was normal. Renal biopsy showed cystic dilatation of the Bowmans spaces and atrophy of the glomerular tufts. Electron microscopy revealed specific changes in the basement membranes of noncystic glomeruli, suggesting a congenital origin for her renal pathology. This relatively rare case contrasts with the usual presentation of GCKD in neonates or children.

Role of Tenascin in Human Immunoglobulin a Nephropathy

Tenascin is a component of the extracellular matrix that responds rapidly to inflammation or injury. The activity index and chronicity index of immunoglobulin A nephropathy are mainly used to decide whether or not steroid therapy is indicated, but are sometimes difficult to evaluate histologically. We investigated whether tenascin staining of the glomeruli was an indicator of the activity or chronicity indices in patients with immunoglobulin A nephropathy. Tenascin staining was evaluated immunohistochemically in 38 renal specimens, including 32 from patients with immunoglobulin A nephropathy and six from control kidneys, and the extent of staining was scored. Tenascin staining was correlated with the chronicity index (r = 0.643, P < 0.0003) but not with the activity index.

Hemodialysis immediately after cardiac catheterization is a risk factor for intradialytic hypotension.

Many hemodialysis clinicians have noticed that patients frequently develop intradialytic hypotension (IDH) immediately after cardiac catheterization (CC). However, precise data about the incidence of IDH immediately after CC are scarce. This study involved a single‐center, retrospective, cross‐sectional design. We reviewed the medical records of all HD patients who underwent CC between January 2009 and March 2012 at Hiroshima Prefectural Hospital. IDH was defined as a fall of systolic blood pressure of more than 20 mm Hg or a fall of mean blood pressure of more than 10 mm Hg, with symptoms according to the K/DOQI criteria. Data on a total of 112 patients were obtained: 64 patients commenced HD immediately after CC (IA group) and 48 patients underwent HD on the day after CC (ND group). The overall incidence of IDH was 34% (38/112). The incidence of IDH was significantly higher in the IA group than in the ND group (27/64, 42% vs. 11/48, 23%; P < 0.05). Multivariate logistic regression analysis showed that IA (odds ratio, 5.39; 95% confidence interval, 1.76 to 16.49; P < 0.01), coronary stenosis (odds ratio, 4.16; 95% confidence interval, 1.49 to 11.64; P < 0.05) were independently associated with IDH. This study revealed that HD immediately after CC is associated with a higher incidence of IDH. Clinicians should consider that HD following CC be scheduled for the next day, especially in patients with coronary stenosis.

Study of the effects of pravastatin in patients with glomerulonephritis associated with hyperlipidemia

Abstract Pravastatin was administered at a dosage of 10 mg/d for 24 weeks to 21 outpatients with glomerulonephritis with accompanying hyperlipidemia who presented with total serum cholesterol levels of ≥220 mg/dL. As a result, significant reductions in total serum cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein (apo) B levels were observed at 12 and 24 weeks after drug administration when compared with the levels observed before treatment (total cholesterol, 308.7 ± 52.3 mg/dL vs 250.8 ± 40.8 mg/dL vs 238.4 ± 34.5 mg/dL; LDL-C, 215.0 ± 47.8 mg/dL vs 158.5 ± 38.4 mg/dL vs 153.0 ± 33.5 mg/dL; and apo B, 143.2 ± 28.3 mg/dL vs 111.3 ± 18.0 mg/dL vs 112.1 ± 19.7 mg/dL; P P

Seasonal variation in hemodialysis initiation: A single-center retrospective analysis

The number of new dialysis patients has been increasing worldwide, particularly among elderly individuals. However, information on seasonal variation in hemodialysis initiation in recent decades is lacking, and the seasonal distribution of patients’ conditions immediately prior to starting dialysis remains unclear. Having this information could help in developing a modifiable approach to improving pre-dialysis care. We retrospectively investigated the records of 297 patients who initiated hemodialysis at Hiroshima Prefectural Hospital from January 1st, 2009 to December 31st, 2013. Seasonal differences were assessed by χ2 or Kruskal-Wallis tests. Multiple comparison analysis was performed with the Steel test. The overall number of patients starting dialysis was greatest in winter (n = 85, 28.6%), followed by spring (n = 74, 24.9%), summer (n = 70, 23.6%), and autumn (n = 68, 22.9%), though the differences were not significant. However, there was a significant winter peak in dialysis initiation among patients aged ≥65 years, but not in those aged <65 years. Fluid overload assessed by clinicians was the most common uremic symptom among all patients, but a winter peak was only detected in patients aged ≥65 years. The body weight gain ratio showed a similar trend to fluid overload assessed by clinicians. Pulmonary edema was most pronounced in winter among patients aged ≥65 years compared with other seasons. The incidences of infection were modestly increased in summer and winter, but not statistically significant. Cardiac complications were similar in all seasons. This study demonstrated the existence of seasonal variation in dialysis initiation, with a winter peak among patients aged ≥65 years. The winter increment in dialysis initiation was mainly attributable to increased fluid overload. These findings suggest that elderly individuals should be monitored particularly closely during the winter.