Hiroshi Inuma

Glomerular deposition of hepatitis C virus in membranoproliferative glomerulonephritis.

Hideaki Yamabe, MD, Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifucho, Hirosaki 036 (Japan) References Johnson RJ, Gretch DR, Yamabe H, et al: Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl JMed 1993;28:465-470. Yamabe H, Johnson RJ, Gretch DR, et al: Hepatitis C virus infection and membranoproliferative glomerulonephritis in Japan. J Am SocNephrol 1995;6:220-223. Doutrelepont JM, Adler M, Willems M, et al: Hepatitis C infection and membranoproliferative glomerulonephritis. Lancet 1993;341:317. Misiani R, Vicari O, Bellavita P, et al: Hepatitis C virus in renal tissue of patients with glomerulonephritis. Nephron 1994;68:400. Dear Sir, Membranoproliferative glomerulonephritis (MPGN) associated with hepatits C virus (HCV) infection has been recently reported [1] and its prevalence may be very high in primary MPGN [2]. This disease is clinically characterized by nephrotic syndrome, active HCV infection, frequent existence of cryoglobulinemia and hypocomple-mentemia and its pathogenesis is assumed to be caused by immune complex including HCV [1,2]. However, the glomerular deposition of HCV has not yet been demonstrated because the amount of HCV may be very small. We tried to detect the glomerular HCV deposition in this disease. Freezed kidney specimens obtained by renal biopsy in 6 patients were examined for glomerular HCV detection. Polyclonal rabbit antibody to HCV core antigen, which was provided by Dr. K. Shimotohno (National Cancer Center, Tokyo, Japan), was used as first antibody in the indirect immunofluorescence techniques. FITC-conjugated goat anti-rabbit IgG (Organon Teknika Co., Durham, N.C., USA) was used as second antibody. Negative control consisted of staining with normal rabbit serum or antibody to HCV absorbed with HCV core antigen, followed by FITCconjugated goat anti-rabbit IgG. Glomerular HCV deposition was observed in 2 of 6 patients with granular manner along the capillary wall and in the mesangium (fig. 1). Doutrelepont et al.

A case of sjögren's syndrome associated with sweet's syndrome

SummaryWe report a case of Sjögrens syndrome whose clinical course had been indolent until the patient presented with Sweets syndrome (acute febrile neutrophilic dermatosis). This patient showed renal failure and renal tubular acidosis. Sweets syndrome resolved within 3 weeks without corticosteroid therapy. Renal biopsy findings were consistent with interstitial nephritis. His renal manifestations responded to corticosteroid therapy and the renal function remained stable during 6 years follow-up without recurrence of Sweets syndrome. Although close association of both syndromes is already known, in our case Sjögrens syndrome may have been exacerbated by occurrence of Sweets syndrome.

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.

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

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.

Worse urinary findings after stimulating tonsils in patients with IgA nephropathy.

Hideaki Yamabe, MD, Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifucho, Hirosaki 036 (Japan) Dear Sir, Although the pathogenesis of IgA nephropathy still remains uncertain, the IgA-type immune complex is presumed to be one of the causative factors of this disease [1]. The predominant deposition of IgA in the glome-ruli makes us consider the role of mucosal immunity in the pathogenesis because of the importance of IgA in immune defense mechanism at the mucosal sites. It is well known that IgA nephropathy patients often show gross hematuria or deteriorated urinary findings after upper respiratory tract infection such as rhinopharyngitis or tonsillitis and it is supposed that the pathogen that causes the preceding infection may play a role as an antigen. It is also suggested that abnormalities of the secretory immune system may exist in IgA nephropathy patients. Several investigators reported the increase of tonsillar IgAse-creting cells [2], the increase of IgA concentration in pharyngeal washings [3] and elevated salivary IgA in IgA nephropathy patients [4, 5]. We speculated that chronic tonsillitis may be involved in the development of IgA nephropathy and tried to clarify the deleterious effect of mechanical tonsil stimulation on urinary findings. The subjects were 62 patients with IgA nephropathy (35 male and 27 female; mean age 26.3 years, age range from 14 to 55 years) and 20 patients with other renal diseases (12 male and 8 female; mean age 29.6 years, age range from 15 to 54 years). Other renal diseases included 11 cases of mesangial pro-liferative glomerulonephritis without IgA deposition, 4 membranous nephropathy, 3 acute glomerulonephritis and 2 idiopathic renal bleeding. Each tonsil was stimulated for 5 min with the Tonsil Provocator (Nagashima Medical Instruments, Tokyo, Japan) producing an ultra shortwave to 40.68 MHz. The probe was put into the mouth until directly attached to the tonsil. A serial quantitative analysis of proteinuria and hematuria was evaluated before, 3 and 24 h after the stimulation. When

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.

Disappearance of Glomerular IgA Deposits in Steroid-Responsive Nephrotic Syndrome

Kazuhiko Fukushi, Second Department of Internal Medicine, Hirosaki University, School of Medicine, Hirosaki (Japan) Dear Sir, Nephrotic syndrome or nephrotic range-proteinuria in IgA nephropathy is generally accepted as one of the possible indicators of a poor prognosis [1]. However, several descriptions of steroidresponsive nephrotic syndrome associated with glomerular IgA deposits, with a feature like minimal change nephrosis, have been recently recognized by several investigators [2–12], and several hypotheses for those occasions are realized at present, but the precise pathognomonic cognition is controversial. In our series of steroid-responsive nephrotic syndrome with IgA deposits, we report 2 patients in whom serial renal biopsy revealed the disappearance of glomerular IgA deposits. Case 1. A 30-year-old man developed edema with a prior history of common cold, and was admitted on January 20,1987. Five years earlier, he had been hospitalized for nephrotic syndrome. Shortly after the diagnosis of IgA nephritis (mesangial proliferative glomerulonephritis) was established (fig. 1), he subsequently received corti-costeroid therapy, just when the nephrotic syndrome was remarkable for complete remission. On this admission, urinalysis revealed 7.0 g of daily proteinuria without hematuria. Total protein was 4.7 g/l00 ml and serum creatinine was 0.8 mg/l00 ml. The profiles of immunological and serological parameters were essentially normal. IgA levels were raised to 512 mg/l00 ml, IgG 585 mg/l00 ml, IgM 135 mg/l00 ml. Percutaneous renal rebiopsy included 10 glomeruli on light microscopic examination that showed mild mesangial proliferative glomerulonephritis. On immunofluorescence, not only IgA but other immunoglobulins and complements were negative. Electron microscopic examination was not studied. Corticosteroid therapy completely relieved nephrotic syndrome. Subsequently, elevated serum IgA levels returned to normal values accompanied by remission of nephrotic syndrome.