Clinical significance of urinary epidermal growth factor levels in patients with acute renal failure.
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Biomedical subjects
Publications and source records attributed to S Koshikawa.
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The authors analysed CD4+ subset populations and particularly subset killing in order to evaluate the presence of antilymphocyte antibody against CD4+ subsets in patients with IgA nephropathy (IgA N). This study was performed in 45 patients with IgA N, 30 patients with other forms of glomerulonephritis and 30 healthy controls. CD4+, CD4+CD45R- and CD4+CD45R+ cells in the peripheral blood were counted by a flow cytometric analysis, and those cell killings were analysed by microcytotoxic assays. The percentage of circulating CD4+CD45R+ cells was significantly decreased in IgA N, and the percentage of CD4+CD45R+ cell killing was significantly elevated in IgA N compared with other groups. There was a significant negative correlation between the percentage of CD4+CD45R+ cells present in IgA N patients' peripheral blood lymphocytes and the killing CD4+CD45R+ cells by the same patients' serum. Both a depletion of CD4+CD45R+ cells in peripheral blood lymphocytes and an elevation of CD4+CD45R+ cell killing correlated with the grade of mesangial proliferation in patients with IgA N. However, there were no correlations in other clinicopathological indices. These results suggest that low levels of antilymphocyte antibodies against CD4+CD45R+ cells were present in patients with IgA N, who showed a depletion of CD4+CD45R+ cells in the peripheral blood. These antibodies were strongly associated with the elimination of CD4+CD45R+ cells and the proliferation of glomerular mesangial cells in patients with IgA N.
Nafamostat mesilate (NM), an ultrashort-acting multi-enzymatic inhibitor, is a useful anti-coagulant in high bleeding risk patients needing hemodialysis. We applied NM as a membrane plasmapheresis (MP) anti-coagulant in patients with high bleeding risk. Eleven patients, the majority with hepatic failure and active hemorrhagic foci or severe bleeding diathesis, could be treated with MP 22 times under anti-coagulation by 20-40 mg/h/NM by continuous infusion without any trouble. Celite-activated coagulation time (CCT) at the plasma separator inlet and outlet was adequately prolonged during MP, but CCT in systemic blood showed no prolongation throughout the procedure, because NM was rapidly inactivated. There was no observable blood coagulation in the extracorporeal circuit including the plasma separator. No adverse reaction or exacerbation of hemorrhage was noted throughout the MP. NM thus appears to be a useful and safe anti-coagulant not only for hemodialysis but also for MP in high bleeding risk patients.
Acid-base disorders are frequently recognized in a wide variety of clinical settings such as severe systemic hospitalized patients. The principal object is to assessment of acid-base equilibrium and to obtain an appropriate guide to therapy. The approach is centered to a systemic analysis of blood gas evaluation. To establish this complex matter is followed. Is an acid-base disorder present? Is the disorder a simple or a mixed abnormality? What is the primary cause? These evaluations should be obtained by accurate history taking, physical examination, and routine laboratory tests. In addition, the supporting analysises such as anion gap (AG) calculation, urine AG assessment, urine chloride concentration and so on are also useful for correct diagnosis. In view of the complexty and difficult expression of acid-base disorders, it is desirable that clinicians must have full knowledges of systemic approach to the blood gas analysis and its evaluation.
Human albumin infusions are frequently administered to patients with nephrotic syndrome. We reviewed the clinical course of 27 patients with minimal change nephrotic syndrome (MCNS) in which 16 patients were treated with human albumin (group A) and 11 were not (group B). The percent of body weight gain, serum total protein, serum albumin, urine protein excretion and renal function were equivalent in both groups as was the initial dose of corticosteroid and amount of dietary protein intake. The period from the start of corticosteroid therapy to complete remission for group A (73.4 +/- 19.2 days, mean +/- SEM) was significantly longer than that for group B (17.1 +/- 3.6), (p less than 0.05). 10 patients of group B (10/11 = 90.9%) showed complete remission within 20 days from the start of corticosteroid therapy, but more than 20 days were needed for 9 cases (9/16 = 56.3%) of group A. Moreover, significant correlations were observed between the period required for remission and the duration of albumin administration (p less than 0.01) or the total volume of albumin infused (p less than 0.01). Proportion of relapsers within 2 years after discharge was also higher in group A (68.8%) than in group B (9.1%), (p less than 0.01). In conclusion, administration of albumin may delay the response to corticosteroid therapy and induce more frequent relapses after remission, possibly due to more severe glomerular epithelial changes induced by albumin infusion in addition to preexisting glomerular epithelial changes from the MCNS.
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In order to evaluate the clinical significance of urinary human epidermal growth factor (hEGF) in patients with acute renal failure (ARF), urinary hEGF levels were determined by radioimmunoassay, and were corrected for creatinine (creat.) concentrations in 16 patients with ARF and 12 healthy controls. The urinary hEGF levels significantly decreased in patients with ARF in acute phase compared with normal control subjects (0.98 +/- 0.20 vs 13.74 +/- 1.18 ng/mg creat. p less than 0.01), and it subsequently increased during recovery phase (6.10 +/- 0.73 ng/mg creat. p less than 0.01 vs acute phase). A significant correlation between the urinary hEGF levels and creatinine clearance (r = 0.712, p less than 0.001) and an inverse correlation between urinary hEGF levels and fractional excretion of sodium (r = -0.406, p less than 0.05) was demonstrated. The remarkable decrease of urinary hEGF excretion preceded the increase of urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase levels. Our data suggests that urinary hEGF originates from renal tissues in humans and measurement of urinary hEGF is useful for diagnosing renal damage and recovery of renal tissues from severe tubular injury.
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The ultrastructure of anionic sites in the lamina rara externa (LRE) of rat glomerular basement membrane (GBM) was studied in three dimensions by a quick-freezing and deep-etching method using polyethyleneimine (PEI) as a cationic tracer. Results were compared with those obtained with conventional ultrathin sections examined by transmission electron microscopy. Examination with the quick-freezing and deep-etching method was done without (group 1) or with (group 2) contrasting/fixation with a phosphotungstic acid and glutaraldehyde mixture and post-fixation with osmium tetroxide, which were necessary for visualization of PEI particles by conventional ultrathin sections. Using the quick-freezing and deep-etching method without following contrasting/fixation and post-fixation (group 1), many PEI particles were observed to decorate around fibrils, which radiated perpendicularly from the lamina densa to connect with the podocyte cell membrane. The arrangement of PEI particles was not as regular as that previously reported using conventional ultrathin sections. In contrast, the tissue that was studied with quick-freezing and deep-etching followed by contrasting/fixation and post-fixation (group 2) showed a shrunken appearance. The arrangement of PEI particles was regular (about 20 particles/1000 nm of LRE) as that previously observed using conventional ultrathin sections. However, the number of PEI particles on the LRE was markedly decreased and interruption of decorated fibrils was prominent, as compared with group 1. Ultrastructural examination using conventional ultrathin sections with contrasting/fixation and post-fixation (group 3) demonstrated PEI particles on the LRE in reasonable amounts (18-21 particles/1000 nm of LRE) with fairly regular interspacing (45-65 nm) as reported previously.(ABSTRACT TRUNCATED AT 250 WORDS)
To clarify the effects of correction of anemia with recombinant human erythropoietin (r-HuEPO) on the hemostatic defects in uremia, hemostatic parameters were examined in 18 hemodialysis patients with renal anemia. Anemia improved significantly 12 weeks after r-HuEPO therapy (stage II) compared to pretreatment (stage I) and 6 weeks discontinuation (stage III) periods. Platelet count did not change among the three stages, however, mean platelet volume increased significantly at stage II in comparison with stage I. Ivy bleeding time (BT) significantly shortened at stage II and prolonged again at stage III. Although there were no significant changes in platelet aggregation, plasma TxB2, 6-keto-PGF1 alpha, F.VIII:C and F.VIII:Ag levels throughout the study, platelet adhesion and von Willebrand factor (vWf):Ag significantly increased at stages II and III. Augmentations in these parameters were more remarkable in BT-shortened patients (n = 12) than in the BT-unchanged group. These results indicate that correction of anemia with r-HuEPO brought about improvement in uremic hemostatic defect via the increase in red cell volume and vWf:Ag, and new production of platelets, reflected by the improvement in platelet adhesion.
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In order to examine the effect on the progression of chronic renal failure (CRF), we have applied an oral adsorbent (AST-120) composed of spherical porous carbon particles to patients with chronic renal failure undergoing conservative therapy. Its effect was observed in improvement of uremic symptoms, improvement of slope in linear regression of reciprocal of serum creatinine vs. time plots and delayed initiation of hemodialysis, compared to control patients, together with reduced uremic peak 2a in HPLC analysis of serum and lower levels of beta 2 microglobulin in AST-120 group than in control. The improvements of uremic symptoms, creatinine and 2a levels were confirmed in double blind study where background of patients were evenly randomized between AST-120 and placebo groups and no improvement was observed in placebo group. The result leads us to conclude that the oral adsorbent therapy is expected as an useful therapy for retardation of progression of CRF.
rhG-CSF (recombinant human granulocyte colony stimulating factor) promotes production and release of neutrophil from bone marrow, and it enhances neutrophil function. In this study, the pharmacokinetics, effects on neutrophil and immune functions and efficacy and safety of rhG-CSF were studied in patients with end-stage renal failure (CRF). To 9 patients with CRF; 2 patients on conservative therapy and 7 patients under regular hemodialysis, 50 micrograms/m2 rhG-CSF were administered intravenously under the schedule of single or 2 week consecutive injection. In single injection study, serial changes in plasma rhG-CSF concentration and peripheral blood cell count were examined following the administration. In consecutive injection study, plasma rhG-CSF concentration, anti-rhG-CSF antibody, peripheral blood cell counts, blood chemistry and coagulation factors, and neutrophil and immune functions were examined. As the results, 1) Half life of rhG-CSF, 2.87 +/- 0.65 hr, was about 2 times longer than that in healthy subjects, and it was not affected by hemodialysis treatment. 2) Marked increase in leukocyte and neutrophil counts and mild increase in lymphocyte count were observed during single and consecutive administration of rhG-CSF. There was no significant change in other leukocyte differentiations, RBC, or platelet count. 3) Neutrophil alkaline phosphatase score increased significantly during single and consecutive administration, and other neutrophil function also improved in several patients with impaired neutrophil function. 4) Slight bone pain and increase in serum alkaline phosphatase were observed in about a half of patients during consecutive injection study. Neither antibody nor accumulation of rhG-CSF was noted.(ABSTRACT TRUNCATED AT 250 WORDS)
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Low protein diet has been a very important clinical manipulation to delay the progression of chronic renal failure. However very low protein diet (less than 30 g/day) is not popular because of concern about malnutrition due to protein restriction, and the difficulty and trouble in making palatable dish. A 48 year old man with chronic renal failure has been on a 20-30 g protein-restricted diet more than three years with no remarkable defect in his daily life, with adequate nutrition, and with very enjoyable and variable daily menus. The rate of progression of chronic renal failure was markedly slowed. Serum creatinine level was 6.9 mg/dl when he started the diet control and it took more than three years for the creatinine level reached to 15.5 mg/dl with no troublesome clinical findings or symptoms. For successful protein restricted dietary treatment, the following several ideas have been helpful: promoting the patient's understanding of the disease and treatment; abundant use of specifically made low protein, high caloric foods such as starch noodles and rice; adoption of creative menus for the patient; and using a free diet a few days a month. The results indicate that we have to again consider the effect of the very low protein (30-20 g/day) diet in slowing the progression of chronic renal failure without nutritional disturbance or restriction of the patient's palatability.