In order to study the effect of high-dose thiazide treatment and low-K diet on citrate uptake by rat renal brush border membrane, we measured citrate uptake by rat renal brush border membrane vesicles (BBMV) and analyzed the acid-base balance of non-treated rats, high-dose thiazide-treated rats and low-K diet rats. Seven-week male Wistar rats (Jcl) were housed in metabolic cages, given 10 mg/Kg BW/day hydrochlorothiazide (HCTZ) by a gastric tube once a day for 3 weeks (high-dose thiazide treated rats) or a low-K diet for 3 weeks (low-K diet rats). Arterial blood was taken from the aorta and BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by a Millipore rapid membrane filtration technique. High-dose thiazide treatment for 3 weeks showed a significant metabolic alkalosis and increase of urinary citrate excretion. However, it had no significant effect on citrate uptake by BBMV. On the other hand, low-K diet for 3 weeks showed significant hypokalemia, metabolic alkalosis and decrease in urinary citrate excretion. Moreover, it increased the maximal activity (Vmax) with no difference in citrate affinity (Km). These data suggested that urinary citrate excretion was more affected by the K depletion than by the acid-base balance.

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In this study, we measured cross sectional areas of glomerular arterioles and glomerular volume in heminephrectomized spontaneously hypertensive rats (SHR) treated with a calcium antagonist, nisoldipine (NSL). We also examined the relevance of these parameters to the progression of hypertensive renal injury. Male 6-week-old SHR (n=14) were heminephrectomized and divided into 2 groups. They were fed regular chow (control, n=7) or chow containing 0.1% NSL (n=7). After 12 weeks, urinary protein excretion (UpV) and systolic blood pressure (SBP) were measured. The control rats developed marked hypertension reaching 228±2 mmHg, and NSL lowered this by 27 mmHg (p<0.001). NSL reduced UpV by 22% (p<0.05). Microvascular cast of the kidney was prepared, and the cross sectional areas of the afferent and efferent arterioles as well as glomerular volume were measured using scanning electron microscopy. In the juxtamedullary and subcapsular glomeruli with minor abnormalities, the afferent arteriole was narrower and the glomerular volume was smaller in the NSL-treated rats than in the control rats. These results suggest that the calcium antagonist, NSL, offers the advantage of protecting kidney from hypertensive injury by reducing afferent arteriolar diameter, glomerular hypertrophy and intraglomerular pressure in heminephrectomized SHR

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The effects of MRX-III, a new amino acid solution for renal failure, on survival, progression of renal insufficiency, metabolism of calcium and phosphorous, and nutritional status were studied in rats with chronic renal failure induced by 7/8 renal ablation. These rats were injected intraperitoneally with MRX-III, an essential amino acid solution for renal failure (Amiyu^(R); Sol. A) or a general amino acid solution (Moripron-F^(R); Sol. M) for 12 weeks under the condition of a 3.5% protein diet, and these effects were compared with those in control rats infused with Sol. M under a 22% protein diet.1) Infusion of MRX-III or the other solutions under a low protein diet prolonged survival time and improved the uremic status indicated by azotemia, polyuria, albuminuria, hypocalcemia and hypertension. 2) Increase in body weight and tissue weight of rats treated with MRX-III or So1. A was better than those in rats treated with Sol. M. MRX-III as well as Sol. A showed a tendency to provide a better nutritional effect in comparison with Sol. M.

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Expression of fibronectin and vitronectin receptors was studied in normal human kidney tissues and renal tissue biopsies from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that fibronectin receptor was present along the glomerular capillary walls, and that vitronectin receptor was present in the vessel walls, but was almost absent from the glomerulus. In kidney tissues biopsied from patients with various renal diseases, expression of fibronectin and vitronectin receptors was correlated with increase in the mesangial expansion. Expression of these receptors was decreased in the sclerosed area and hyalinized glomeruli compared with normal tissues. Fibronectin and vitronectin receptors were occasionally colocalized in the glomeruli with fibronectin and vitronectin, respectively. In situ hybridization showed that fibronctin recep tor mRNA and vitronectin receptor mRNA were expressed in the diseased glomeruli. These findings indicate that expression of fibronectin and vitronectin receptors was altered in human glomerulonephritis, and that integrin expression may be important in cell-matrix interaction in the diseased glomeruli.

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It is not certain whether the life expectancy of patients with membranous nephropathy is shorter than that of an age-matched healthy population. Forty-one patients (21 males, 20 females) aged between 16 and 70 years (average age: 33.3 years) were followed for 20 years. The patients were divided into two groups: group I (n=18), consisting of patients in whom nephrotic syndrome persisted for more than two years or until death, and group II (n-23), consisting of patients except for group I . The non-survival criteria are death or renal death. Twelve patients (29.3%) died during the study period. Eight patients belonged to group I and 4 to group II. The causes of death in group I patients were end-stage renal failure in 3 cases, ischemic heart disease in 1 case, subarachnoid hemorrhage in 1 case, malignancy in 2 cases, suicide in 1 case, and those in the group II patients were pneumonia, malignancy, cerebral softening, and diabetes mellitus, respectively. Eight patients who died in group I had a significantly longer difference between their actual life span (ALS) and life expectancy (LE) and a significantly smaller ratio of ALS to LE than the patients who died in group II (ALS-LE: -29.9±4.5 years in group I vs. -9.0±6.8 years in group II, p<0. 05, ALSx 100/LE: 22.5±8.0% in group I vs. 80.9±25.2% in group II, p<0.05). In group I, the ratio of observed to expected death was 4.76 (95% confidence interval, 2.05 to 9.37) and significa-ntly higher than that of the control population. In group II, however, the ratio was 1.09 (95% confidence interval, 0.30 to 2.80), and the difference from the control population was not statistically significant. These results suggest that longstanding nephrotic syndrome is associated with a shortened life expectancy in patients with membranous nephropathy.

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Coagulation and fibrinolytic factors in the blood were measured during heparinurokinase (UK)-pulse combined therapy in order to investigate the background for the availability of the therapy. Five patients with nephritis resistant to conventional treatment were treated with this combined therapy (heparin:350-450 U/kg day, continuously i.v.during the therapy;UK:5000 IU/kg/2hrs, i.v., two times a day, for 3 days=l Kur; methyl-prednisolone 20mg/kg/2hrs, d.i.v., for 3 days=l Kur; 3 Kurs of UK and 3 Kurs of pulse were alternately administered).1) Blood levels of α2-plasmin inhibitor (α2PT) antigen were decreased and those of α2-plasmin inhibitor· plasmin complex (α2-PI. PmC) were elevated during 3 Kurs of UK administration.Accordingly, activation of the fibrinolytic system was confirmed during the combined therapy, suggesting that both α2-PI and α2-PI·PmC were relevant in monitoring the fibrinolytic state in blood.2) Both tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAT-1) levels were sustained continuosly in the elevated levels in the blood during both UK administration and pulse therapy. This movement of t-PA and PAI-1 was independent of that of the other fibrinolytic factors, such as α2-PI, α2-PI·PmC and plasminogen.3) Inflammatory reactants such as fibrinogen, α2-PI, α2macroglobulin and α1-antitrypsin decreased more significantly during this heparinurokinase-pulse combined therapy than during our previous combined therapy consisting of only heparin and urokinase. Therefore, we conclude that the anti-inflammatory effect was reinforced by adding the pulse therapy and that the combined therapy had some effect on the release of t-PA from vascular endotherial cells

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Decreased plasma level of antithrombin III was assumed to be one of the major factors underlying hypercoagulable state in nephrotic syndrome. Concentrated antithrombinIII preparation was given to 8 children with nephrotic syndrome with a plasma antithrombin III activity of less than 70%, to evaluate the effect on hypercoagulable state. Plasma antithrombin III activity was elevated to more than 70% in 7 of 8 children after treatment, while plasma levels of plasmin-α2 plasmin inhibitor complex and FDP-D dimer were not significa-ntly decreased. One patient developed brain infarction after the treatment, suggesting that prophylactic administration of concentrated antithrombin III preparation is not fully protec-tive against thrombotic complications in nephrotic syndrome.

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Cardiovascular complications, such as vascular calcification (VC), have been a major concern in patients undergoing chronic dialysis. The pathogenesis of this VC has been attributed to the altered calcium and phosphate metabolism, but the contributing factors have not been clarified. In order to investigate these factors, 38 CAPD patients were divided into two sub-groups according to the absence of aortic calcification (Group-A; n=18) or the presence of aortic calcification (Group-B; n=20).The number of elderly patients was larger and the duration of CAPD was longer in Group-B than in Group-A.Calcium and phosphate metabolism and serum lipids levels did not differ significantly between groups and the number of patients given VD was 8/18 in Group-A and 14/20 in Group-B. In order to explore the progression of VC in CAPD patients given long-term treatment with VD, 22 patients who were matched for the duration of CAPD were analyzed. These were divided into two sub-groups according to whether they were treated with VD (Group-C; n=11) or not treated with VD (Group-D; n=11). Radiological findings (such as the degree of aortic calcification), bone mineral content, divalent ions, parathyroid hormone levels and lipid profiles were examined. The prevalence of patients with aortic calcification was significantly higher in Group-D than in Group-C (7/11v.s.2/11, P<0.05).However, lipids, mineral and endocrinological parameters did not differ between the sub-groups. No significant difference in the calcium and phosphate balance was observed. The bone mineral content revealed no difference between both of the sub-groups. VD administration by conventional mode, even without significant suppression of PTH or increase of bone mineral content, may enhance vessel calcification in patients on long-term CAPD.

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The prevalence and the clinical significance of hepatitis C (HCV) infection in recipients of kidney transplantation was assessed using second generation anti-HCV antibody (anti-HCV-2). Out of 88 patients whose preoperative sera were available for anti-HCV-2 determi-nation, 27 patients (30.7%) were positive. Transfusion units were significantly larger and the duration of hemodialysis was significantly longer in the patients with anti-HCV-2 than those without. In 10 patients whose preoperative sera were negative for anti-HCV-2, seroconver-sion was documented after the operation, so that the postoperative positive rate of anti-HCV -2 increased to 42.9% (39/91). Seroconversion from positive to negative was observed in only one patient. Out of 91 patients who were followed-up at least 3 months after operation, 66 patients (72.5%) developed liver dysfunction. According to the criteria of non-A, non-B post-transfusion hepatitis established by the Japanese Society of Digestive Disease, 31 of 66 patients (34.1%) were diagnosed as "definite", 21 patients (23.1%) as "suspicious". The anti -HCV-2 positive rate was 90.3% in the "definite" group, which was significantly higher than the other groups. Liver dysfunction in the patients with anti-HCV-2 had a tendency for a chronic or prolonged course. Out of 20 patients in whom liver dysfunction continued for more than 1 year, 18 patients were positive for anti-HCV-2. It is concluded from this study that the prevalence of hepatitis C is very high in kidney transplant recipients with HCV as the main and most important etiologic factor of liver dysfunction, especially in chronic liver impairment.

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We present two cases of hypercalcemic nephropathy associated with primary hyperparathyroidism. Case 1 is a 37-year-old man who had repeated bone fractures and recurrent ureteral stones, which led to the diagnosis of primary hyperparathyroidism. Case 2 is a 35-year-old man in whom parathyroid carcinoma was discovered because of secondary nephrogenic diabetes insipidus, resulting from severe hypercalcemia. Both patients developed mild renal dysfunction during the course of hyperparathyroidism. In the renal biopsy materials obtained from case 1, the renal interstitium showed chronic inflammatory changes. The tubules were partly damaged (focal necrosis). Deposition of calcium was someties noted within the mitochondria of the tubular epithelial cells. Some glomeruli showed glomerular sclerosis. In biopsy materials obtained from case 2 after resection of the carcinoma, similar histological features were observed, but tubular atrophy and necrosis were advanced. Polyuria and hypercalcemia were ameliorated after resection. These findings indicate that severe hypercalcemia might induce tubular dysfunction as well as organized changes.

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We reported a case of type II cryoglobulinemia involving glomerulopathy associated with HCV-induced liver cirrhosis. The patient was a 57-year-old woman. Her past history included chronic hepatitis at 51 years and rheumatoid arthritis at 53 years of age. At 46 years, an erythematous lesion appeared on her legs, which was diagnosed as allergic vasculitis by skin biopsy. At 50 years, proteinuria, hematuria and hypertension were recognized. The next year, the first renal biopsy was performed and showed membranoproliferative glomerulonephritis (MPGN). Recently, the edema of her legs has progressed, and the laboratory data showed proteinuria, hematuria, hypocomplementemia, rheumatoid factor positivity, and increase of monoclonal IgG κ chain. The second renal biopsy revealed an endocapillary proliferative glomeruonephritis-like lesion with marked infiltration of monocytes and macrophages. The subendothelial deposit showed a fine fibril-like pattern. She was treated with steroids and double filtration plasmapheresis (DFPP) therapy, but the treatment was not very effective. She died of liver cirrhosis, which was probably induced by hepatitis C virus (HCV), and sepsis. Generally, the patients of type II cryoglobulinemia often showed HCV antibody positivity, pointing to HCV as an etiological factor. In this case, renal biopsy was performed twice in the same patient, and the histologic findings suggest the clinicopathological course of cryoglobulinemia.

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It has been described that a rapid worsening in renal function is uncommon in the elderly patient with lupus nephritis. We report a case of a 76-year-old man with rapidly progressive lupus nephritis. On admission, laboratory studies revealed massive proteinuria, telescoped urine, thrombocytopenia and azotemia. Hypocomplementemia and the positive presence of anti-DNA antibody and lupus anticoagulant were also noted. Because of a rapid deterioration of renal function, he was started on a regimen of steroid pulse therapy and plasmapheresis. Serum levels of complements gradually increased after initiation of these treatments, and three weeks later, improvements of renal function and nephrotic syndrome were obtained. A renal biopsy specimen taken five months after admission showed diffuse membranous glomerulonephritis. In addition, we examined renal arterial blood flow with Doppler ultrasound, and significant improvements of the velocity and pulsatility were observed during recovery of the renal function.

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