Significance of urinary fibrin/fibrinogen degradation products (FDP) D-dimer measured by a highly sensitive ELISA method with a new monoclonal antibody (D-D E72) in various renal diseases.

To diagnose the abnormalities of coagulation-fibrinolysis in various renal diseases, we developed a new monoclonal antibody (D-D E72) against fibrin/fibrinogen degradation products D-dimer (FDP D-dimer) and established a highly sensitive enzyme-linked immunosorbent assay (ELISA) for its measurement. FDP D-dimer was assessed in 102 patients with various renal diseases, and the following results were obtained: 1. The mean level of urinary FPD D-dimer in 32 normal controls was 0.69 +/- 0.60 ng/ml (mean +/- SD). 2. The level of urinary FDP D-dimer was significantly higher in primary nephrotic syndrome group (NS), chronic renal failure group (CRF) and in the group of diabetic nephropathy (DM) than in the control group. However, no difference was observed in the level of urinary FDP D-dimer between non-nephrotic chronic glomerulonephritis group (CGN) and control group. 3. No significant correlation was revealed between D-dimer and urinary protein in CGN and NS groups. These results suggest that in addition to plasma filtration the urinary FDP D-dimer in NS, CRF and DM may be also related to abnormalities of secondary fibrinolysis in intra-glomerular fibrin deposits.

[Tuberculosis in patients undergoing hemodialysis].

The incidence of tuberculosis is very high in patients treated by hemodialysis particularly in the early stage of hemodialysis. The diagnosis of tuberculosis in dialysis patients was obscured as symptoms were nonspecific and extrapulmonary involvement was seen frequently. We investigated cell mediated immunity in dialysis patients in relation to the period of dialysis. The data indicate that dialysis patients show the following immunological impairments; 1) lymphopenia, 2) decreased B cell, 3) alteration of T cell subset, 4) decreased reaction of PPD skin test, 5) decreased T cell activity, 6) decreased IL-2 production, 7) decreased PHA induced lymphocyte blastogenesis, 8) decreased NK cell. Decreased immunologic host defence mentioned above may contribute to the high incidence of tuberculosis in the early stage as well as in the maintenance phase of dialysis.

[Measurement of secretory IgA in salivary juice and the localization of secretory IgA in duodenal mucosa in patients with IgA nephropathy].

In order to clarify whether or not the local IgA immune system plays a role on the pathogenesis of IgA nephropathy, we measured serum levels of IgA, serum and salivary levels of secretory IgA in patients with IgA nephropathy and in healthy subjects, and compared them with the results of immunohistochemical study of the duodenal mucosa obtained from patients with IgA nephropathy and healthy subjects. The results were as follows. 1. The serum levels of IgA were significantly higher in patients with IgA nephropathy than in healthy subjects. 2. The salivary levels of secretory IgA were significantly higher in patients with IgA nephropathy and non IgA nephropathy than in healthy subjects. 3. There was no significant difference in the serum levels of secretory IgA between patients with IgA nephropathy and healthy subjects, but they were significantly higher in patients with hematuria than without hematuria. 4. The salivary levels of secretory IgA were lower in some patients with IgA nephropathy, in spite of the intense staining of the secretory component and J chain in the duodenal mucosa, than in healthy subjects. On the other hand, the salivary levels of secretory IgA were lower in other patients with IgA nephropathy, in addition to the weak staining of secretory component and J chain in the duodenal mucosa than in healthy subjects. These results suggested that the disorder of IgA mucosal immunity may contribute to the pathogenesis of IgA nephropathy.

Charge distribution of plasma IgG and IgG immune complexes in IgA nephropathy.

IgA nephropathy is characterized by a predominant deposition of IgA in the glomerular mesangium. However, in many cases, deposition of IgG also occurs and the concentration of circulating IgG immune complexes is higher than that in controls. To examine further the possible role of the charge of immunoglobulins in the pathogenesis of IgA nephropathy, we used isoelectric focusing (IEF) and densitometry to investigate the charge distribution of plasma IgG and IgG immune complexes in patients with this disease. Blood samples were taken from patients and healthy adults, and plasma and samples treated with 7.0% polyethylene glycol (PEG) were used. All samples were focused with a Multiphor II flatbet electrofocusing unit apparatus on an agarose gel, then immunofixed with polyclonal goat anti-human IgG, and stained with Coomassie blue R 250. The stained gels were analyzed by densitometry. 1. In plasma, the areas of PI 10-8.9 and PI 10-8.6 in IgA nephropathy were higher in the patients than in the controls. 2. In the 7.0% PEG precipitation, the area PI 8.1-6.1 was higher in the patients than in the controls. These findings suggest that a change in charge distribution of IgG and IgG immune complexes may contribute to the pathogenesis of IgA nephropathy.

A case report of allergic granulomatosis and angiitis (Churg-Strauss syndrome) with a review of the literature.

We report the case of a 67-year-old man with allergic granulomatosis and angiitis (AGA; Churg-Strauss syndrome) who developed nephrotic syndrome during his clinical course and demonstrated membranous nephropathy on renal necropsy by electron microscopy. Following the development of symptoms of bronchial asthma accompanied by eosinophilia and mononeuritis multiplex, transbronchial lung biopsy confirmed a diagnosis of AGA. The patient died of pneumonia and disseminated intravascular coagulopathy, but necropsy revealed severe tubulo-interstitial damage with neutrophilic infiltration and, in half of the glomeruli, mesangial proliferation with subepithelial dense deposits. This paper thus describes a rare case of AGA complicated by a secondary type of stage I membranous nephropathy.

[Significance of urinary fibrin/fibrinogen degradation products (FDP) measured by highly sensitive ELISA method in various renal diseases].

In order to clarify the abnormalities of intra-glomerular coagulation and fibrinolysis in patients with various renal diseases, urinary fibrin/fibrinogen degradation products (FDP) have been examined by several methods. We established a highly sensitive new method of enzyme-linked immunosorbent assay for urinary FDP. The results were as follow: 1) The mean +/- SD of urinary FDP in normal subjects was 10.30 +/- 9.08ng/ml. 2) The urinary FDP levels in chronic glomerulonephritis, nephrotic syndrome and chronic renal failure patients were significantly higher than normal subjects, and the levels in SLE, Alport's syndrome patients were higher than normal subjects. 3) The urinary FDP levels were a little bit higher in the patients with proliferative glomerulonephritis than in chronic glomerulonephritis patients with minor lesion or membranous nephropathy. 4) There was significant correlation between urinary FDP and urinary protein in chronic glomerulonephritis, while there was no correlation in nephrotic syndrome. 5) There was no correlation between urinary FDP and intra-glomerular fibrin deposits examined by immunofluorescent study in chronic glomerulonephritis, while in nephrotic syndrome, there were high levels of urinary FDP in the positive fibrin deposits cases. These results suggested that the most of the part of excretion of the urinary FDP in chronic glomerulonephritis is associated with the filtration of blood FDP to urine through the glomerular basement membrane, while in the nephrotic syndrome cases the origin of urinary FDP is related to the filtration and/or the intra-glomerular coagulation abnormalities.

A case of nephrotic syndrome associated with ischemic colitis exhibiting thickening of the colon wall.

The patient was a 54-year-old male with proteinuria, which was first noted in 1984. Recently, the patient experienced aggravation of the proteinuria, which resulted in nephrotic syndrome. Renal biopsy revealed findings compatible with membranous nephropathy. While being treated with prednisolone (30 mg/day), the patient experienced intense abdominal pain of sudden onset, diarrhea, and melena. A tumor was demonstrated by abdominal ultrasonography and CT scan. A diagnosis of ischemic colitis was made by colonoscopy. FDP and fibrinogen levels were elevated, and abnormalities of the coagulation and fibrinolytic factors were found at the onset of the symptoms.

A case of nephrotic syndrome associated with traumatic chronic osteomyelitis.

A 19-year-old male developed nephrotic syndrome during the course of chronic osteomyelitis complicating a traumatic suppurative arthritis of the knee. Renal biopsy revealed severe mesangial proliferative glomerulonephritis, and immunofluorescent microscopy demonstrated the presence of IgA. Nephrotic syndrome remitted during the treatment for chronic osteomyelitis, suggesting a close association of the two conditions.

[Significance of urinary fibrin/fibrinogen degradation product (FDP) D-dimer measured by highly sensitive ELISA method with a new monoclonal antibody (D-D E72) in various renal diseases].

In order to clarify the abnormalities of the coagulation and fibrinolysis system in patients with various renal diseases, we produced a new monoclonal antibody for FDP (fibrin/fibrinogen degradation product) D-dimer (D-D E72). We also established a new highly sensitive method of enzyme-linked immunosorbent assay (ELISA) for urinary FDP D-dimer using this monoclonal antibody. The urine from 110, patients with various renal diseases was investigated for the FDP D-dimer. The results are summarized as follows: 1) Urinary FDP D-dimer in normal subjects was 0.69 +/- 0.60 ng/ml. 2) The level of urinary FDP D-dimer in patients with primary nephrotic syndrome and in patients with chronic renal failure was significantly higher than that of normal subjects, whereas the urinary FDP D-dimer levels in patients with diabetes mellitus were higher than those of normal subjects. 3) In the CGN and NS groups there was a tendency for an increase in the level of urinary FDP D-dimer in more active forms of the disease. 4) A significant correlation between urinary FDP D-dimer and urinary protein in the CGN and NS groups was demonstrated. 5) In all of the renal diseases investigated in this study, the ratio of urinary FDP D-dimer to total FDP was less than 4%.

[Anti-glomerular basement membrane antibody-mediated glomerulonephritis remarkably improved by pulse therapy with methylprednisolone, plasmapheresis and continuous heparin infusion].

The patient, a 28 year-old-man, was admitted to a hospital because of general fatigue and fever. He was pointed out renal dysfunction and was transferred to Nagasaki University Hospital. The laboratory data on admission showed moderate azotemia (BUN 43 mg/dl, Cr 5.4 mg/dl). A percutaneous renal biopsy on admission revealed a diffuse crescentic glomerulonephritis. A direct immunofluorescence of renal biopsy showed a linear pattern for IgG along the glomerular basement membrane. Radioimmunoassay of his serum for circulating anti-GBM antibody was strongly positive. Aggressive treatment with pulse therapy (methylprednisolone), plasmapheresis, and continuous heparin infusion was performed. He had markedly recovered from renal failure and escaped hemodialysis. The patient is making satisfactory process after 3 years.

Significance of urinary fibrin/fibrinogen degradation products in renal diseases measured by a highly sensitive ELISA.

The urinary fibrin/fibrinogen degradation products (FDP), as sensitive indicators of various renal disorders, have been measured by several methods. For their determination, a new and highly sensitive enzyme-linked immunosorbent assay not requiring the urine concentration has been developed. The study comprised 42 patients with nonnephrotic chronic glomerulonephritis (CGN), 23 patients with primary nephrotic syndrome (NS), and 29 healthy adults. The results were as follows: (1) the content of urinary FDP in normal subjects was 10.30 +/- 9.08 ng/ml; (2) the mean level of urinary FDP in both CGN and NS groups was significantly higher than in normal subjects; (3) in the CGN group itself there was a tendency for an increase of urinary FDP during more active forms of the disease, and (4) there was a significant correlation between urinary FDP and urinary protein in the CGN group, whereas no correlation was observed in the NS group. These results suggest that the major part of urinary FDP in the CGN group derives from the increased filtration, while its origin in the NS group is not related to increased filtration only, but may also have involved intraglomerular coagulation abnormalities. The newly developed enzyme-linked immunosorbent assay can detect urinary FDP levels lower than 3.9 ng/ml. Therefore, this method can be of great value in determining the degree of abnormalities of intraglomerular coagulation and fibrinolysis in renal diseases.