Rabbit antisera were produced against antigens obtained from pharyngeal cell of patients with IgA nephropathy (IgAN). Extracts of pharyngeal cells from patients with IgAN were frozen and thawed, and the supernatants were cocultured with fibroblasts (Vero and Hel cells). Pieces of renal biopsy specimens of the same patients were sectioned and centrifuged. The supernatants which contained IgA were incubated with the fibroblasts, and were stained with FITC-labeled anti human IgA antisera. Two positive (A and B) and one control Vero cell lines were destroyed and centrifuged. The precipitates were injected into rabbits, and rabbit antisera (A, B and control) were produced. Renal tissues from patients with IgAN and proliferative glomerulonephritis without IgA deposition (PGN) were stained with the FITC-labeled antisera.Positive stainings with FITC-labeled antiserum A was observed in 87% and that with FITC-labeled antiserum B in 55% of the patients with IgAN. No positive staining was detected with FITC-labeled control antiserum. There was also no positive staining with these antisera in renal tissues with PGN. The immunological specificity of the antisera was evaluated. It was found that these antisera did not react with complements components or immunoglobulins. The above findings suggested that some antigens from pharyngeal cells were deposited in the glomeruli from IgAN patients.

抄録全体を表示

We induced aminonucleoside (AN) nephrosis in male Sprague-Dawley rats and evaluated the decreases in negative charge in the peripheral and proximal portions of the loop basement membrane and the basement membrane in the paramesangial area. Following intravenous injection of polyethyleneimine (PEI), the number of PEI granules per 0.1μm² of the basement membrane, and those per 1μm length of the lamina rara externa (LRE) and lamina rara interna (LRI) were counted in each portion under an electron microscope and compared with those in the control group. In the rats with AN nephrosis, the number of PEI granules per 0.1μm² was significantly decreased in each portion of the basement membrane. However, the degree of decrease was similar among the 3 portions. The ratio of the numbers of granules in the proximal and paramesangial portions to that in the peripheral portion (peripheral:proximal:paramesangial) was 1:0.89:0.64 in the control group and 1:0.88:0.62 in the AN nephrosis group. Similar results were obtained for the numbers of PEI granules per 1μm length of the LRE and LRI. These findings suggest that the negative charge is decreased in the loop basement membrane and paramesangial basement membrane in AN nephrosis, but the degree of decrease appears to be uniform.

抄録全体を表示

In order to study the localization of Lentil lectin (LCH)-binding glycoresidues in glomeruli from patientsith a variety of glomerulopathies, and to elucidate the relationship between LCH-binding sugars and the components of the extracellular matrix, laminin and type IV collagen, investigations of formalinfixed, paraffindembedded kidney tissues digested with trypsin were carried out by the direct and indirect imrnunofluoresceiice microscopy techniques. The glomerular basement membrane (GBM) and the rnesangium reacted well with LCH, whereas areas with sclerotic lesions exhibited a decreased reactivity.The pattern of I., CH binding to the GBM in various glomerulopathies was similar to that of laminin but different from that of type IV collagen. The pattern of localization of LCH-reacting sites and of laminin in the GBM included the double linear lines in diabetic nephropathy, inner linear line with outer projections (spikes) in membranous nephropathy, and reduplicated basement membrane in rnembranoproliferative glomezulonephritis. The results obtained by enzymenlinked immunoadsorbent assay showed that LCH had a stronger reactivity for laminin than for type IV collagen or fibronectin. These findings suggest that LCH is more reactive with lammin than with other components of the glomerular extracellular matrix.

抄録全体を表示

To produce a compatible model of early renal failure easily, we prepared three-quarters nephrectomized animals. 20 Sprague-Dawley rats were divided into the following two groups: 10 rats which received threequarters nephrectomy (Nx group), assuming the weight of both kidneys to be equal, and another 10 rats which underwent sham operations (S group). The levels of creatinine clearance in Nx group and S group were 286.5±33.5 vs. 431.1±55.9μl/min/100 g BW (P <0.001) on week 2, and 233.0±16.7 vs. 562.3±62.9μl/min/100 g BW (P<0.001) on week 10, respectively. The indirect and direct systolic blood pressure (SBP) values of Nx group and S group at the 10th week were 154.5±5.5 vs. 131.1±3.6 mmHg (P <0.01), and 148.2±4.8 vs. 130.7±6.6 mmHg (P <0.01), respectively. Significant changes in the levels of urinary protein excretion, urinary sodium output, urinary epinephrine, urinary norepinephrine and plasma renin activity between both groups were recognized on the 10th week. The planar area of Nx group was significantly increased as compared to that of S group (11.0±0.3 vs. 7.2±0.1X10-3 mm2, P<0.001). It is concluded that this model resembles early renal failure in humans because slow progression of renal dysfunction occurred with mild elevation of SBP, and that it is adequate for evaluating the influence of glomerular hypertrophy, resulting in glomerulosclerosis.

抄録全体を表示

Lytic changes to the mesangium and subendothelial area in diabetic glomerulosclerosis were studied by electron microscopy with an emphasis on the mechanism of nodule formation. Renal biopsy specimens were obtained from 30 diabetics (11 males, 19 females; 27 NIDDM, 3 IDDM; mean age, 52.2 years) with renal involvement. Evaluations were made of the glomerular lesions, particularly the ultra-structural findings contributing to nodule formation, mainly by electron microscopy. Varying degrees of lytic change, such as a loose and edematous mesangial matrix, widening of the subendothelial space, followed by endothelial detachment, and destruction of anchor points, were observed in close association with progression of the diffuse lesions. Plasma proteins were found to infiltrate into the widened subendothelial space. Mesangial cells also protruded into the same space and encroached around the whole capillary wall. The interposed mesangial cells were occasionally separated from the basement membrane. Monocytes identified from their ultrastructure were frequently present noticed in the lytic areas, suggesting a reaction to lytic changes. These processes may occur repeatedly with direct expansion of the mesangial matrix, subsequently revealing a nodular appearance.

抄録全体を表示

We analyzed the components of urinary proteins in 58 diabetic patients with either short duration or long-standing disease using sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (SDS-PAGE), in comparison with 21 healthy volunteers. It was found that the percentage of protein with a molecular weight (Mr) of 140 kDa was greater in diabetics with normal renal function and negative clinical proteinuria (<100 mg/24 h) than in normals. In patients with clinical proteinuria (>100 mg/24 h), the percentage of protein with an Mr of 67 kDa (presumably albumin) was predominantly increased, while the percentage of lower Mr proteins was considerably decreased. A positive correlation existed between the total urinary protein excretion and the percentage of 67 kDa protein in diabetics without clinical proteinuria (r = 0.487, p <0.01), but not in normal subjects. Recovery of glycemic control led to a decrease of urine proteins with an Mr lower than 67 kDa, while deterioration of the control resulted in an increase in these proteins. The present data confirm the idea that analysis of the components of urine proteins by SDS-PAGE represents a useful approach to understanding the glomerular and tubular functions in diabetic patients. Additionally, this investigation appears to provide biochemical evidence that dysfunction of the glomerular permselectivity to plasma proteins might already have occurred in diabetic patients without clinical evidence of diabetic nephropathy.

抄録全体を表示

The phosphate kinetics during bicarbonate dialysis (BCD) and Acetate-free Biofiltration (AFB) were determined in 3 stable regular dialysis patients. These patients were switched to a 6-month period of AFB after a 12-month period of BCD. The plasma levels of phosphate, urea, and bicarbonate, and mass removal of phosphate and urea were measured every hour, during 3 consecutive dialysis sessions on BCD and AFB. The plasma phosphate behavior revealed a peculiar form with two main components, which differed from that of urea. The plasma phosphate level fell sharply during the first 2 hours of treatment, and then remained at a plateau towards to the end of the session. The plasma bicarbonate levels during the treatment sessions in the case of AFB were significantly higher than that in BCD. The actual mass removal in AFB was similar to that BCD, despite a significantly lower value of pre-plasma phosphate. A high ultrafiltration rate and better control of acidosis might be the reason for the better performance of phosphate mass removal in AFB. Better control of phosphatemia due to AFB can lead to a reduction in the amount of phosphate binders which have several untoward side effects.

抄録全体を表示

The present study documents the occurrence of renal failure in 4 nephrotic patients including 3 with minor glomerular lesions and one with membranoproliferative glomerulonephritis. One patient died of sepsis at 3 months after onset of the acute renal failure. In the remaining 3, forced diuresis employing albumin plus furosemide in increasing doses to 600 mg/day reversed the renal failure independent of corticosteroid therapy. All of the 4 patients showed characteristic findings consisting of a remarkably low fractional excretion of sodium and an unexpectedly low urine osmolality at the onset of acute renal failure, although they were rather hypervolemic. Our findings suggest that the occurrence of a low fractional excretion of sodium and low osmolality may provide a good index of an absolute indication for intensive weight reduction therapy such as high-dose furosemide in nephrotic patients with acute renal failure in order to reverse the acute renal failure.

抄録全体を表示

Uremic patients often complain of fatigue and muscle weakness. In order to elucidate the abnormalities of energy metabolism in the muscles of such patients, we measured the concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and adenosine triphosphate (ATP) as well as the intracellular pH in skeletal muscles by 31P-NMR at rest, during aerobic and anaerobic exercise and during recovery in 15 uremic patients (7 non-dialyzed patients and 8 dialyzed patients) and 6 control subjects. At rest, there was no difference in intracellular pH between the uremic patients and controls, but the concentrations of PCr and ATP in the skeletal muscle were lower in the uremic patients. However, during aerobic exercise, the uremic patients showed a rapid decrease in intracellular pH and a delay in its recovery. They also revealed an increased PCr utilization during aerobic exercise and its delayed resynthesis during recovery. During anaerobic exercise, the uremic patients, especially non-dialyzed patients, displayed a slower decrease in pH than the controls and a delay in its recovery. An increased PCr utilization during anaerobic exercise and a delayed resynthesis during recovery were also demonstrated. These findings suggest that the aerobic and anaerobic energy productions in uremic patients are impaired and that the energy production of the muscle depends on anaerobic glycolysis during exercise. Hemodialysis apparently facilitates recovery of the inhibited enzyme activities of oxidative phosphorylation and glycolysis in uremic patients.

抄録全体を表示

As an approach to the geopathological evaluation of kidney disease, we conducted a comparative study on IgA nephropathy (IgANP) between Saga Medical School (SMS) in Japan and Kosin Medical College (KMC) in Korea for the period 1983-1987. The relative incidence of IgANP among primary glomerular diseases was significantly higher (P.(0.05) at SMS (103 cases of IgANP among 250 cases of primary glomerular diseases, 41.2%) than at KMC (63 cases among 201 cases, 31.3%). Clinical and histological comparisons of the IgANP between the institutions revealed that the SMS series was generally milder than the KMC series. When the renal manifestations at the time of biopsy for all cases with primary glomerular diseases were compared, asymptomatic urinary abnormalities were more commonly found at SMS than at KMC. This suggests that certain differences in medical practice may exist between the two institutions, as follows: l) the medical checkup system may be more efficient, 2) the accessibility to medical service may be easier, and 3) the biopsy criteria may be more liberal in Japan/SMS than in Korea/KMC. Thus, the real differences in incidence and severity of IgANP between the two institutions could be smaller than those reported here.

抄録全体を表示

The renal disease in an adult woman with Type 1 glycogen storage disease (GSD) is reported. Since she was 15 years old, several episodes of gouty arthritis had developed. At the age of 18, proteinuria was pointed out. Hepatomegaly, renomegaly out of proportion to the impairment of renal function, hyperuricemia, hyperlipidemia, fasting hypoglycemia and lactic acidemia were observed. The diagnosis of GSD was established on the basis of a glucose tolerance test, glucagon test and liver biopsy. The findings of renal biopsies performed at the ages of 24 and 27 years old suggested that glomerular damage might have preceded the tubulo-interstitial lesion.

抄録全体を表示

A case of IgA glomerulonephritis associated with renal cell carcinoma is reported. A 61-year-old male was admitted because of a left renal mass and proteinuria. A diagnosis of renal cell carcinoma was made by computed tomography and angiography. Left radical nephrectomy was performed. Microscopically, the tumor tissue revealed renal cell carcinoma of the clear cell type. Light, immunofluorescent and electron microscopic examinations demonstrated characteristic features of IgA glomerulonephritis. The proteinuria and hematuria disappeared 8 months after removal of the tumor. These findings suggest that the IgA glomerulonephritis in our patient may have been attributable to an immune response against the renal cell carcinoma.

抄録全体を表示

Acute renal failure (ARF) associated with primary nephrotic syndrome (PNS) was analyzed clinically in order to evaluate the mechanism of onset. The incidence of induced ARF with PNS was found to be cases (2.1%) out of 420 cases attending our outpatient clinic. The renal histological changes included 2 cases of minimal change nephrotic syndrome (MCNS), 6 of focal glomerular sclerosis (FGS) and one of unknown origin. The 6 cases which recovered from ARF were designated as group A. The 3 cases of group B required maintenance dialysis; they included one case of MCNS, one of FGS and one of unknown origin, and showed resistance to aggressive treatments, such as steroid pulse therapy, anticoagulants and plasmapheresis. In the patients of group A, follow up studies for 10 years confirmed that their condition was not progressive. There were no significant differences between the reversed group A cases recovering from ARF and the non-reversed group B cases in terms of their clinical parameters, such as age, sex, urinary protein excretion, initial renal function, blood pressure, renal histological damage and complications. Specific factors associated with the induction of reversibility from ARF could not be identified. Further research is needed to elucidate the precise characteristics of the ARF occurring in PNS.

抄録全体を表示

The present study deals with intraglomerular lipid deposition and its relation to the development of focal glomerular sclerosis (FGS) in rats. Experimental FGS was induced by repeated administration of puromycin aminonucleoside (AN) and was observed from the 3rd to 6th month. At 3 months after the beginning of the experiment, FGS lesions, marked proteinuria and hyperlipidemia were observed. Sudan III-stained sections revealed intraglomerular deposition of lipid, especially in the sclerotic lesions. An immunofluorescent study demonstrated nodular or massive deposition of IgM, IgG and fibrinogen in the sclerotic areas. Significant positive correlation was observed between the degree of intraglomerular lipid deposition and glomerular damage. In order to examine the intraglomerular lipid, isolated glomeruli which were obtained by a sieving method were analyzed by thin layer chromatography. The intraglomerular lipid consisted of cholesterol ester with a small amount of triglyceride. The incidence of sclerosis and excretion of urinary protein attained peak levels at the 3rd month and then decreased, but hyperlipidemia was prolonged. It is suggested that hyperlipidemia and intraglomerular lipid deposition may contribute to the development of FGS in aminonucleoside nephrosis.

抄録全体を表示