Kazuhiro Ozawa

IgA Nephropathy and Henoch-Schönlein Purpura Nephritis with Anterior Uveitis

Two patients with IgA nephropathy and a patient with Henoch-Schönlein purpura nephritis each associated with anterior uveitis are described. As anterior uveitis accompanying IgA nephropathy improved, renal manifestations were relieved. The patient with Henoch-Schönlein purpura nephritis suffered from not only anterior uveitis but also keratitis. It is suggested that immune mechanisms which induce IgA nephropathy may play a role in the development of anterior uveitis and keratitis.

Case Report of Amyloidosis-Like Glomerulopathy with Hepatic Involvement

A few cases of nephrotic syndrome with the glomerular deposition of an amyloid-like material which did not stain with Congo red have been documented. But extrarenal deposits have not been previously reported in this disease. We describe here a case of nephrotic syndrome associated with the deposition of an amyloid-like material in the liver as well as in the renal glomeruli. The deposits were made up of fibrillar structures which resembled those of amyloid when viewed through the electron microscope but they did not stain with Congo red. This is the first report of amyloidosis-like glomerulopathy with extrarenal deposits.

Glomerular Deposition of Hageman Factor in IgA Nephropathy

Glomerular localization of Hageman factor and fibrin-related antigen (FRA) was examined in 31 cases of IgA nephropathy by immunofluorescent techniques. Hageman factor was observed in 21 cases (68%) and FRA in 24 cases (77%). It is suggested that blood coagulation occurs and fibrin is formed in the glomerulus of IgA nephropathy.

Elevated serum secretory IgA in patients with IgA nephropathy.

Serum secretory IgA was measured to elucidate the significance of secretory IgA in patients with IgA nephropathy. The levels of serum secretory IgA and IgA were, respectively, 6.8 +/- 3.5 micrograms/ml and 231.0 +/- 69.2 mg/dl in the controls and 11.8 +/- 3.2 micrograms/ml and 385.3 +/- 78.7 mg/dl in the patients. The levels of serum secretory IgA and IgA in the patients were significantly higher than those in controls (p less than 0.01). Elevated serum secretory IgA may reflect the excessive state of the IgA-secreting system in IgA nephropathy patients.

Mechanism of Urinary Erythrocyte Deformity in Patients with Glomerular Disease

Hiroharu Kubota, MD, Second Department of Internal Medicine, Hirosaki University, School of Medicine, 5 Zaifucho, Hirosaki 036 (Japan) Dear Sir, Birch and Fairley [1,2] and Birch et al. [3] described glomerular bleeding giving rise to a wide range of morphological alterations in red cells such as dysmorphic red cells. In these alterations, we suspect that the doughnut type of deformity is the most characteristic (fig. 1). The mechanism of urinary erythrocyte deformity in patients with glomerular disease is considered to be the result of continuous changes in osmotic pressure and urinary pH in tubuli [2, 3]. However, in our experiments no doughnut-type erythrocytes were seen under osmotic pressure changes and there were no differences in urinary pH between the dysmorphic group (48 cases) and isomor-phic group (35 cases). In glomerular hematuria, another important factor was the passage of erythrocytes through the glomerular capillary wall composed of endothelium, basement membrane and foot process of epithelium [4, 5]. In view of the important finding that erythrocytes were distorted by passage through the ruptured glomerular capillary wall, we carried out further experiments as follows. 1 ml venous blood in 100 ml saline was incubated at 38 ¤C for 30 min. About 50 mm Hg pressure was applied to the suspended erythrocytes filtered by 3 kinds of membrane filters (pore size: 5 and 3 μm, fibrin-coated 5-μm narrowing in size). The filtrates were examined by phasecontrast microscopy and scanning electron microscopy. In this experiment, doughnut-type erythrocytes were seen in the fibrin-coated 5-μm membrane filter group and

Elevated Salivary IgA in Patients with IgA Nephropathy

Elevated Salivary IgA in Patients with IgA Nephropathy H. Yamabe K. Ozawa K. Fukushi H. Ohsawa N. Chiba K. Onodera 2 Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan H. Yamabe, 2 Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki 036 (Japan) Dear Sir, Secretory IgA, which exists in mucosal surfaces of respiratory and digestive tracts, provides the primary defense mechanism against some local infections owing to its abundance in saliva, tears, bronchial secretions and mucous secretions of the small intestine [1]. It is well known that many patients with IgA nephropathy show deteriorated urinary findings when they have an upper respiratory tract infection. But there has been little interest in secretory IgA because it was not detected in the glomeruli [2, 3]. We examined salivary IgA to elucidate the significance of secretory IgA in IgA nephropathy patients. Saliva was obtained without any stimulus from 21 patients with IgA nephropathy and 16 normal controls. Salivary IgA and serum IgA were measured simultaneously by single radial immunodiffusion. The mean levels of salivary IgA and serum IgA were 24.1 ± 10.4 and 266.9 ± 100.9 mg/dl in the controls, 40.0 ± 16.1 and 414.6 ± 98.1 mg/dl in the patients. The levels of salivary IgA and serum IgA were significantly higher in the patients than in the controls (p < 0.001). There was a positive correlation between salivary IgA and serum IgA (r = 0.44, p < 0.01; fig. 1). All salivary IgA is secretory IgA. Secretory IgA is different from serum IgA in its origin, molecular weight and immunological property. It is widely recognized that the patients with IgA nephropathy often have elevated serum IgA, the causes of which remain unexplained. The reason of elevated salivary IgA is also unknown. Bene et al. [4] reported an imbalance in the IgAproducing system of patients with IgA nephropathy. They mentioned that the number of tonsillar IgA-secreting cells was higher than that of IgG-secreting cells in the patients, while the opposite was observed in the controls. Elevated salivary IgA may be caused by the change of the IgAsecreting system in IgA nephropathy.

Intraglomerular Lipid Deposition in Experimental Focal Glomerular Sclerosis in the Rat

Hiroshi Ohsawa, Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifucho, Hirosaki Aomori 036 (Japan) Dear Sir, It is well known that focal glomerular sclerosis is observed in rats by administration of puromycin amino-nucleoside (AN). Although the pathogenesis of glomerular sclerosis in this model is still unknown, some hypotheses have been reported, such as mesangial overloading [1]. A recent report [2] suggests that chronic renal disease may be mediated by abnormalities of lipid metabolism. We studied the intraglomerular lipid deposition in this model and analyzed the intraglomerular lipid. AN (1.5 mg/l00 g of body weight) was injected daily, first for a week, and then again 6 weeks later. AN-treated rats and control rats were sacrificed monthly from the 3rd to the 6th month. Kidney tissues were observed by light microscopy and electron microscopy. To examine the intraglomerular lipid deposition, sections stained with Sudan III were observed and lipid extracted from isolated glomeruli was analyzed by thin layer chromatogra-phy. Isolated glomeruli were obtained by the sieving method. At the sacrifice, blood was sampled to measure total protein, creatinine and lipid according to the standard method. Urinary protein was measured by sulfosali-cylic acid method. After 3 months, 87% of the glomeruli revealed glomerular sclerosis in AN-treated rats. Electron microscopy showed that the main pathologic change in sclerosis was an increasing of mesangial matrix. Lipid deposition was seen in 95% of the sclerotic glomeruli, especially in the sclerotic lesions. Morphological changes were not observed in control rats. Serum levels of total protein and creatinine were normal in each group. Significant pro-teinuria and hyperlipemia were observed in AN-treated rats, but not in control rats. Thin layer chromatography revealed that the intraglomerular lipid consisted of cholesterol ester and triglyceride (fig. 1). Grond et al. [1,3] suggested that mesangial accumulation of macromolecular substance leads to glomerular sclerosis [1, 3]. The lipid deposition has some relation to the development of focal

A case of anti-nuclear antibody negative systemic lupus erythematosus associated with penile ulcer

SummaryWe report here an old male patient with anti-nuclear antibody (ANA) negative systemic lupus erythematosus (SLE) with active renal disease and penile ulcer. He revealed nephrotic syndrome, malar rash and oral ulcer. SLE was discussed, however both ANA and anti-DNA antibody were persistently negative. A penile ulcer was also observed. He died of acute respiratory distress. Autopsy findings including onion skin lesion in the spleen and haematoxylin body in the kidney resulted in the final diagnosis of SLE. To our knowledge, association of penile ulcer with SLE has not yet been reported. Therefore, the present case is thought to be extremely unusual.

Electron Microscopic Studies on IgA Nephropathy

We carried out electron microscopic studies on renal tissues from 9 patients with IgA nephropathy. Electron dense deposits were present in the mesangial area in all cases, subendothelial deposits in 4, and subepithelial deposits in only one. In basement membrane, segmental swelling and rarefaction of basement membrane substance were observed. In some cases the degenerated basement membrane substance protruded through the dilated endothelial fenestration into capillary lumina. Focal splitting, attenuation, mouse eaten appearance, and herniation of basement membrane were seen in a high incidence. Mesangial cells possessed well developed rough endoplasmic reticulums and polysomes. In the peripheral areas of mesangial cell cytoplasm, there was accumulation of electron dense substance and this was occasionally continuously present in the mesangial matrix. There was segmental swelling of endothelial cell cytoplasm, resulting in loss of fenestration. Epithelial cells had well developed rough endoplasmic reticulums and polysomes. Segmental foot process fusion was seen, and these processes, regardless of fusion, became electron denser in the area close to the basement membrane. Multivesiculated bodies were present in all cases in the epithelial cells and in 7 cases in the endothelial cells. Spherical microparticles were present in 3 cases in the urinary space or between the basement membrane and the epithelial cells.

Therapeutic Approach for the Deteriorated Renal Function in IgA Nephropathy

Our experience concerning a prospective randomized trial of a cocktail scheme of prednisolone, cyclophophamide and warfarin or dipyridamole for deteriorated renal function in IgA nephropathy is reported.