To elucidate the mechanisms by which factors in the digestive tract influence the progressive chronic renal failure in rats, we employed the oral adsorbent, AST-120, which can adsorb certain uremic toxins in the gastrointestinal fluid. Administration of AST-120 firstly delayed the appearance of systemic hypertension, secondly delayed the increase in the amount of urinary protein excretion, and finally delayed the emergence of glomerular hypertrophy and glomerulosclerosis . The data obtained did not provide evidence for an inhibitory effect of AST-120 on hypertension. Our results therefore suggest that a pressor substance or its precursor exists in the digestive tract of rats with chronic renal failure .

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The effects of tannins purified from Rhei Rhizoma on various parameters of renal function were investigated in rats with adenine-induced renal failure . The glomerular filtration rate, renal plasma flow and renal blood flow were significantly increased in rats given (-)-epicatechin 3-O-gallate at a dose of 5 or 10 mg/kg body weight/day for 24 days. Administration of 5 mg of procyanidin B-2 3, 3′-di-O-gallate also led to a significant increase in renal functional parameters . However, unlike the former two components, procyanidin C-1 3, 3′, 3″-tri-O-gallate caused aggravation of renal function .

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The expression of glomerular extracellular matrix receptors of the very late a ntigen (VLA) family was examined in the human renal glomerulus by indirect immunofluorescence studies. β1 subunits of integrin were localized in glomerular epithelial, endothelial and mesangial cells and Bowman's capsule . α3 integrin was localized dominantly in the glomerular capillary wall and less in the mesangium and Bowman's capsule. α2, α4 and α5 integrins were barely stained in the glomerulus. Our findings indicate that the VLA family of integrins plays an important role in the attachment of glomerular cells to the extracellular matrices.

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Intraglomerular coagulation and fibrinolysis could be involved in the exacerbation of renal diseases, and urinary fibrin/fibrinogen degradation products (FDP) may be applicable as an index. Although the urinary FDP can be estimated by the latex agglutination method, this technique has disadvantages such as a poor sensitivity and is of the semiassay type. Recently, a new method of measurement which improves on these disadvantages, termed the latex photometric immunoassay (LPIA) method, has been developed. However, since FDP measurement by LPIA was designed for the purpose of serum FDP estimation, a measurement technique for urinary FDP has not yet been established. The purpose of the present study was to devise a measurement procedure for urinary FDP employing the LPIA method, and to obtain data on the normal levels of urinary FDP in healthy subjects. The results obtained may be summarized as follows. (1) The urinary pH and coexistent substances such as bovine serum albumin, glucose, urea, bilirubin, ascorbic acid, and hemoglobin, did not influence the urinary FDP measurement. (2) No changes in urinary FDP were observed after 28-day storage at -20°c or -80°c in the presence or absence of tranexamic acid. (3) The coefficient of variation was 5.3%. (4) The normal level of FDP excretion was 3.33±7.95 μg/day. The present data demonstrated that the LPIA method enables the urinary FDP to be measured quantitatively with a good sensitivity.

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It is possible that abnormalities of intraglomerular coagulation and fibrinolysis are involved in the exacerbation of kidney diseases. Urinary fibrin/fibrinogen degradation products (FDP) are regarded as an index of the intraglomerular coagulation and fibrinolysis. Although the conventional latex agglutination method for detecting urinary FDP has disadvantages such as a poor sensitivity and is of the semiassay type, latex photometric immunoassay (LPIA), a recently developed technique, is an assay with a high sensitivity. The present study was undertaken in an attempt to clarify the significance of urinary FDP as measured by latex photometric immunoassay in renal diseases. The subjects comprised were 60 patients with 15 kinds of renal diseases. Occasional urine samples and blood samples withdrawn at the time of urinary collection were examined. The FDP and F'DP-E fractions (FDP-E) were measured by LPIA, and the FDP-D fraction (FDP-D) and fibrinopeptide A (FPA) were measured by enzyme immunoassay. The highest level of urinary FDP was seen in cases with diabetic nephropathy, followed by renal amyloidosis and chronic glomerulonephritis. While no correlation was noted between the urinary FDP levels and blood FDP levels, positive correlations were observed among the urinary protein, urinary FDP-E, FDP-D and FPA. The urinary FDP also reveled an inverse correlation with the 1/serum creatinine. All cases with high levels of urinary FDP displayed renal dysfunction. These findings suggest that quantitative assay of the urinary FDP using LPIA is important for determining the degree of abnormality of intraglomerular coagulation and fibrinolysis in renal diseases.

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The aim of the present study was to clarify the role of intrarenal coagulation in the progression of renal dysfunction and to assess the efficacy of anticoagulant therapy in diabetic nephropathy patients. Forty-one diabetic patients were divided into 2 groups: group 1(G-1), 20 patients with nephropathy; and group 2 (G-2), 21 patients without nephropathy. The levels of fibrinopeptide A (FPA) and fibrinopeptide B_15-42s(FPBβ_15-42), fibrin/fibrinogen degradation products-D dimer (FDP-D dimer), and FDP-E products (FDP-E) and FDP, which are sensitive parameters of coagulation and fibrinolysis, were measured by radioimmunoassay, enzyme immunoassay (ETA), and latex photometric immunoassay, respectively, in both the blood and urine. The levels of urinary FPA, FDP-D, FDP-E, and FDP were found to be much higher in G-1 than in G-2. Significant relations were observed among the urinary levels of these four parameters. The renal function in all cases with higher levels of urinary parameters was severely deteriorated. Following heparin administration to these patients, marked reductions of the urinary FPA, FDP-D, and FDP-E and improvement of nephrotic syndrome were observed. The present data suggest that in diabetic nephropathy:(1) intrarenal coagulation is likely to occur and to induce progression of renal dysfunction; and (2) heparin therapy could be effective in diabetic nephropathy when the patients are selected according to the above parameters of coagulation and fibrinolysis.

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It has been found that polycystic kidney (ADPKD) is often associated with gout. On the other hanj, there are reports describing that the hyperuricemia (HU) seen in ADPKD corresponds to a reduction in renal function. We investigated the uric acid metabolism in 44 patients with ADPKD (age, 50±12.8 years; C_CR, 50.5±41.1 ml/min) at our hospital. From among these 44 patients, 14 with a C_CR of 80 ml/min were selected. Their data for uric acid metabolism were compared against those from the previous year's studies on various disease types (114 normal subjects, 70 with membranous nephropathy, 175 with IgA nephritis, 122 with gout, 137 with asymptomatic hyperuricemia, and 42 with diabetes mellitus). Among the 44 patients with ADPKD, the serum uric acid (S_UA) was 7.7±1.9 mg/dl and HU affected 28 (63.6%). The incidence of gouty arthritis was also high (6 patients, 13.6%), revealing a positive correlation between S_UA and C_CR. Compared with membranous nephropathy and IgA nephritis, ADPKD exhibited an accentuated increase in S_UA associated with a reduction in C_CR. It is believed that this represents a factor for a high incidence of complications of hyperuricemia and gouty arthritis in ADPKD in contrast to other diseases. However, no increase in the production of uric acid was noted in ADPKD.

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Hydroxyproline (HYP) is an amino acid which is highly specific for bone collagen . Measurement of HYP provides an index of bone resorption, although the usefulness in this respect of the serum free HYP, which is the easiest HYP fraction to determine, has not yet been established. In the present study, the serum free HYP was measured using the method of Dabev et al., and the data were compared against other parameters of renal osteodystrophy (ROD). In comparison with values for the normal control group (n=10), the serum free HYP was significantly elevated in the patient group with conservatively treated end-stage renal failure (n=14) and in the patient group on chronic hemodialysis (n=107), with the latter group showing the highest value. Also, in the group with radiographic evidence of bone resorption, the free HYP exhibited a significant elevation. Significant positive correlations were noted between the free HYP and both the parathyroid hormone (PTH) and alkaline phosphatase (Al-P) levels . When the subjects undergoing bone biopsy were divided according to their histological findings into an increased osteoid group and an increased osteoid+resorption group, the latter displayed a significantly higher free HYP value. In addition, the free HYP values were low in the group administered lα-OH-D ₃ and showing only slight bone resorption.These results suggest that since the free HYP closely reflects accelerated bone resorption in ROD and is easier to measure than non-protein-bound HYP, it can serve as a clinically useful index of ROD.

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Although various simplified calculation formulae of Kt/V-urea based on urea kinetic modeling have been reported, all the formulae include errors such as post-dialysis urea rebound and urea generation during a dialysis session. In the present study, in order to calculate the precise Kt/V-urea, a formula of Kt/V-urea, taking into account post-dialysis plasma urea rebound and urea generation during a dialysis session (Kt/V-P) was proposed, and compared to other formulae already published, in 49 dialysis patients without residual renal function (26 M and 23 F; mean age, 65±2 years; mean dialysis duration, 70±7 mos). The precise post-dialysis plasma urea concentration was significantly higher than the actually measured post-dialysis plasma urea concentration by approximately 12%, and Kt/V-P corresponded to Kt/V-urea=In(Ci/Cf) with the best correlation in the formulae utilized in the present study, around 1 of Kt/V-urea, which is clinically the most important range. It is concluded that Kt/V-urea=In(Ci/Cf) is the most suitable formula for the calculation of Kt/V-urea, when post-dialysis plasma urea rebound and urea generation during a dialysis session are taken into account.

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We investigated how long continuous ambulatory peritoneal dialysis (CAPD) could be continued in the face of peritoneal sclerosis. 15 CAPD patients with no experience of peritonitis were selected and the time limitation for CAPD was examined retrospectively, based on the dialysate osmolality, serum creatinine concentration, etc.. The values for the dialysate osmolality and serum creatinine concentration increased gradually with the duration of CAPD and were significantly increased from 6 months. 5 patients whose serum creatinine concentration during the first 6 months after initiation of CAPD increased more than 5 mg/dl, could not continue CAPD for more than 24 months because of the appearance of peritoneal membrane failure. When the time limitation for CAPD was assessed in 10 stable patients, close relationships between the mean dialysate osmolality and duration of CAPD (Y=0.52×+351.25, r=0.83, P<0.01), and between the mean serum creatinine concentration and duration of CAPD (Y=0.18×+6.84, r=0.95, P<0.001) were recognized. If the practical limitation for CAPD was set at 400 mOsm/l in terms of the dialysate osmolality or 20 mg/dl in terms of serum creatinine concentration, its value became 94.1 months or 73.1 months, respectively. It is concluded that the time limitation for CAPD can be expected to be approximately 6 to 8 years in stable CAPD patients, and we need to resolve CAPD-induced problems involving the peritoneal membrane in order to continue CAPD for more than 10 years.

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The present report describes a rare case of hematophagic histiocytosis associated with acute renal failure. A 32-year-old woman was referred to us from a local hospital because of progressive deterioration of renal function, jaundice and a bleeding tendency. The physical findings at admission revealed hyperemic conjunctivae, gingival bleeding, hepatomegaly, and generalized myalgia. Laboratory data indicated a decrease in platelet count, azotemia and hyperbilirubinemia. Marked elevation of serum triglycerides and ferritin was also noted. Histiocyte proliferation with phagocytosis of erythrocytes and platelets was observed in a bone marrow aspirate. A renal biopsy specimen exhibited lesions generally observed in acute tubular necrosis:degeneration and necrosis of tubular epithelial cells; round cell in filtration and edema in the interstitium; and unremarkable glomeruli. The serum titer to coxsackievirus B1 rose from<4× at admission to 16 × after recovery from the illness, suggesting that this virus may have been the causal organism of the accompanying infection. The patient's symptoms improved rapidly with supportive therapy, and complete restoration of renal function was achieved in 20 days . The morphological characteristics of the bone marrow aspirate and the clinical course were compatible with hematophagic histiocytosis.

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We report the renal immunohistochemical findings of a patient with thrombotic thrombocytopenic purpura complicated with systemic lupus erythematosus. Aggregated platelets were observed adhering to the arteriole walls. Intense deposition of von Willebrand factor (vWF) was noted in the endothelium, even in areas where thrombi were not seen. This difference in the distribution of platelets and vWF suggested that the endothelium was damaged prior to platelet aggregation.

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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.

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The requirements for a diagnosis of Goodpasture's syndrome (GPS) include:(1) the presence of glomerulonephritis, (2) alveolar bleeding, and (3) the presence of anti-glomerular basement membrane (anti-GBM antibody). Among Japanese case, the 2 patients reported here were rare in that they satisfied all of these requirements. In case 1 (a 40-year-old male), the disease developed with initial signs of proteinuria and hematuria. The patient developed hemoptysis after hospitalization. The interval from onset to hospitalization was 38 days. The serum creatinine (CRN) level was 3.6 mg/dl on admission. The pathological findings were rated as full-circumferential, cellular crescentic nephritis, and the patient did not display oliguria. The renal and pulmonary impairments in this case were markedly improved by glucocorticoid (prednisolone PSL, 60 mg/day), cyclophosphamide therapy (50 mg/day) and plasma exchange (PE 10 times). In case 2 (a 58-year-old male), the initial signs developed as proteinuria and hematuria, followed by rapidly progressive renal functional deterioration and hemoptysis occurred. Compared to Case 1, the interval from onset to hospitalization was longer in Case 2 (125 days) and the CRN level was also higher (10.7 mg/dl). Case 2 was rated as full-circumferential, fibrous crescentic nephritis, and the patient was oliguric. Although the pulmonary impairment was reduced by pulse therapy and 10 PE_s, recovery of renal function has not been achieved, still necessitating maintenance hemodialysis at present. In case 1, the disease relapsed at 4.5 years after remission, presenting with aggravated renal function and hemoptysis. In this case, low-dose PSL therapy had been discontinued at 3 months before the relapse. Following the relapse, the pulmonary impairment was reduced by hemodialysis, PE and pulse therapy, but recovery of renal function has not been achieved, so necessitating maintenance hemodialysis. In general, the percentage of complete remission is high for GPS, but some patients showing relapse have also been reported. The anti-GBM antibody titer, whose determination has become possible in recent years, is expected to represent a useful index in the prevention of relapse of GPS and in the management of patients during gluco-corticoid therapy.

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