摘要:

It is envisaged that circulating IgA complexes play a primary role in the glomerular injury of IgA nephropathy, the most common glomerulonephritis worldwide. In this study, we examined the pathophysiological effects of IgA and IgG isolated from IgA-nephritic patients on the signal transduction of human neutrophils. Heat-aggregated forms and monomers of IgA and IgG were prepared from sera of 11 IgA-nephritic patients and 11 healthy controls. Signal transduction was studied by measuring the inositol triphosphate (IP3) production in neutrophils incubated with the immunoglobulin preparations. Different forms of IgA or IgG from IgA-nephritic patients failed to induce a significant increase in IP3 production directly as compared with control IgA or IgG. However, neutrophils preincubated with heat-aggregated IgA (HAA) from IgA-nephritic patients demonstrated a significant rise in IP3 production upon subsequent stimulation by a chemotactic peptide, FMet-Leu-Phe (FMLP); a similar finding was not observed with heat-aggregated IgG. HAA pretreatment of neutrophils increased FMLP-induced IP3 production in a dose-dependent manner. The raised IP3 production was not due to increased FMLP receptors, as HAA preincubation of neutrophils did not increase the binding of tritiated FMLP. The increased IP3 production upon FMLP stimulation in HAA-primed neutrophils was completely abolished by pertussis toxin in a dose-dependent manner. These findings tend to refute a direct stimulatory effect of HAA on phospholipase C, but, instead, may suggest that HAA prepared from IgA-nephritic patients upregulates the activation of G proteins in the plasma membrane. Our data suggest that HAA prepared from IgA-nephritic patients exert an upregulatory effect on signal transduction in neutrophils. These findings indirectly support the view that neutrophils are activated in IgA nephropathy and that they may play a contributory role in the inflammatory process of glomerular and interstitial injury.

ISSN:1660-8151    

DOI:10.1159/000188352

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In order to analyze the relationship between lipoprotein (a) [Lp (a)] and other lipoproteins during chronic renal failure and once renal function is restored after kidney transplantation, we determined the serum levels of total lipoprotein, high-density lipoprotein, low-density lipoprotein, and very-low-density lipoprotein cholesterols, total and very-low-density lipoprotein triglycerides, apohpoproteins A-I, B, C-II, C-III, and E, and E, and Lp (a) in 30 patients with chronic renal failure before and 12 months after renal transplantation. During the 1st year after transplantation, all patients were treated only with ciclosporin and prednisone and had serum creatinine levels < 1.6 mg/dl (140 μmol/l) and proteinuria < 500 mg/day. No patients had chronic hepatic disease. To determine reference values we studied a control group of 60 healthy volunteers. Before renal transplantation, the study group showed higher concentrations of triglycerides, very-low-density triglycerides, very-low density lipoprotein cholesterol, apohpoproteins, C-II and C-III, and Lp(a) than the control group. There was no correlation between Lp(a) and any of the studied variables. After renal transplantation, the serum levels of total lipoprotein, high-density lipoprotein, and low-density lipoprotein and apohpoproteins A-I and B increased significantly. Apohpoproteins C-II and C-III and Lp(a) decreased and normalized. After these changes had taken place, there was no relationship between Lp(a) and other parameters of lipoprotein metabolism. We conclude that the increase in Lp(a) during the chronic renal failure phase is basically related to the loss of renal function and does not depend on the resultant alterations which are produced in other lipoprotein variables

ISSN:1660-8151    

DOI:10.1159/000188353

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Renal cortex in 15 cases with Itai-itai disease was morphometrically examined, i.e. the cross-size of tubuli in the renal cortex was measured using a color image analyzer (Olympus CIA-102) and the ratio of preserved urinary tubuli occupying renal cortex was calculated by means of the point-counting method. The former and the latter decreased gradually together as atrophy of kidney advanced. However, their decrease was stopped at about 60 g of kidney weight and it was inferred to be the limit of histopathologic changes of the kidneys with Itai-itai disease. Comparing the cross-size of the tubuli of the outer cortex area [=S(o)] with one of the inner cortex area [=S(i)], changes were more marked in S(o). This revealed that the outer cortex area was more sensitive to Cd intoxication and it was more affected by systemic atherosclerosis than the inner cortex area. It was concluded that when atrophy of kidneys as seen with Itai-itai disease was extremely progressing, decreases in the number and volume of tubuli in the cortex usually occurred at the same time and in a regular manner.

ISSN:1660-8151    

DOI:10.1159/000188354

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The nephrotic syndrome (NS) carries one of the highest risks of thrombotic complications. Consequently, over the last 15 years, some nephrologists have treated patients at risk (i.e. those with albuminemia < 20 g/l and membranous nephropathy) with anticoagulants: either subcutaneous heparin (Kakkar protocol) or antivitamin K. Low-molecular-weight heparin (LMWH) has a longer plasma half-life and better bioavailability than standard heparin and can thus be administered as a single daily injection. LMWH also carries a lower risk of hemorrhage. We prospectively studied the safety and efficacy of the LMWH Enoxaparin for preventive anticoagulation in NS. In a preliminary study, 10 adult nephrotic patients with biological markers of thrombosis risk (severe hypoalbuminemia and/or anomalies of the fibrinolytic pathway and/or deficiency in coagulation inhibitors) were given 40 mg (4,000 U) of Enoxaparin daily for at least 3 months; 3 patients were treated for 3 months, 1 for 6 months and 6 for 12 months. Patients were assessed for silent thrombosis, using renal vein Doppler ultrasonography, lower leg vein Doppler ultrasonography and lung ventilation-perfusion scintigraphy, before entry to the trial and subsequently at 3-month intervals. As LWMH caused no obvious side effects and no thrombosis was observed during the pilot study, we then placed 55 adult nephrotic patients free of thrombosis on the same treatment. Patients were seen according to the usual calendar required by their individual illnesses. At each examination, patients were assessed for clinical signs and symptoms of thrombosis and side effects; plasma D-dimer and urinary fibrin-fibrinogen degradation products were also measured at each visit. Twenty-five of the 55 patients (minimal-change disease, n=15; membranous nephropathy, n=2; systemic lupus erythematosus, n=2; other forms of glomerulonephritis, n = 6) received LMWH for less than 4 months. No side effects or thrombosis were observed, with the exception of 1 patient who had local intolerance to Enoxaparin but not to Teldeparin. The other 30 patients (membranous nephropathy, n=14; segmental glomerulosclerosis, n = 13; other nephropathies, n=3) received LMWH for at least 6 months (median, 13 months; range, 6-48 months). No side-effects or thrombosis were observed. Enoxaparin caused no changes in bone density in patients at risk of osteoporosis, as determined by absorptiometry. The self-administered LMWH therapy was well accepted by patients, most of whom found it straightforward and painless. The results of this prospective study suggest that the LMWH Enoxaparin given at a dose appropriate for adult NS patients with a high thrombotic risk is safe, effective and easily self-administered. The incidence of bleeding was low. Our findings provide arguments for the adoption of LMWH as first-line preventive anticoagulation in NS.

ISSN:1660-8151    

DOI:10.1159/000188355

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Fifteen patients (10 males, 5 females) on regular hemodialysis treatment (average age 43.6 ± 4.0 years, average time on dialysis 100.7 ± 62.8 months) underwent cerebral computed tomography between 1981 and 1984. Ten patients showed mild cerebral atrophy (CA) on the basis of cortical sulci exceeding 3 mm in breadth and an Evans ratio exceeding 0.31, for a total of 14 degrees of CA (mean 0.9+1). The same 15 patients underwent a second cerebral computed tomography during 1991/92 (101 ± 23.7 months later). At that time, the patients exhibited a degree of CA of 2.6 ± 1.4, for a total of 39 degrees with an overall increase of 25 degrees. Since CA is not detected before the age of 55 years in the normal population, we conclude that the CA in this patient group can only be attributed to uremia-related pathology and that it tends to worsen as regular hemodialysis treatment continues. Nevertheless, no evident cognitive, affective, or behavioural changes were verified in these patients. To our knowledge, this is the first presentation of radiologically documented progression of CA in the same patient population over t

ISSN:1660-8151    

DOI:10.1159/000188356

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Aluminum catalyzes the oxidation of NADH by vanadate both in the presence and absence of a reducing sugar. The effect of aluminum is concentration dependent and inhibitable with superoxide dismutase but not catalase. The fructose-6-phosphate-free reaction is characterized by an initial lag phase which can be eliminated by preincubating aluminum with NADH, but is not altered by preincubating aluminum with vanadate, suggesting that the effect of aluminum is not directly on vanadate. Aluminum also catalyzes vanadyl-mediated oxidation of NADH, and this effect is similarly inhibitable by superoxide dismutase as well as catalase. It is suggested that aluminum catalyzes the oxidation of NADH by vanadium though enhancing the production of superoxide radicals and that this effect may account in part of the biological toxicity associated with aluminum, particularly when associated with the accumulation of other trace elements such as vanadium..

ISSN:1660-8151    

DOI:10.1159/000188357

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Several studies have shown that long-term therapy with angiotensin-converting enzyme inhibitors may reduce urinary protein excretion and decrease the rate of progression of renal disease in patients with insulin-dependent diabetes mellitus more effectively than conventional antihypertensive drugs. Only few studies, however, have been performed in patients with non-insulin-dependent diabetes mellitus (N1DDM). To compare the effects of captopril with more conventional drugs on proteinuria and progression of renal disease, we conducted a prospective, 18-month study in 42 proteinuric ( > 500 mg/day) NIDDM and, for comparison, in 31 nondiabetic patients with a variety of renal diseases (NDRD). Twenty-four NIDDM patients were treated with captopril and 18 with conventional drugs. Eighteen NDRD patients received captopril, and 13 received conventional drugs. Baseline proteinuria and glomerular filtration rate (GFR) were not different among groups. The blood pressure decreased equally in all group of patients, irrespective of whether they received captopril or conventional drugs. Urinary protein excretion, however, decreased significantly only in NIDDM and NDRD patients treated with captopril. The GFR decreased only in patients treated with conventional drugs, but not in those treated with captopril. The rate of decline in GFR in NIDDM patients treated with captopril was significantly lower than in patients treated with conventional drugs. However, in NDRD patients treated with captopril, the rate of decline in GFR was not different from that in patients treated with conventional drugs. The reduction of urinary protein excretion was poorly correlated with changes in blood pressure or with changes in renal function and renal hemodynamics. Serum potassium increased significantly in patients treated with captopril. These results have shown that in patients with NIDDM and NDRD long-term therapy with captopril may reduce urinary protein excretion and retard the progression of renal disease more effectively than conventional antihypertensive therapy.

ISSN:1660-8151    

DOI:10.1159/000188358

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Urea kinetic modeling (UKM) by a two-sample method (UKM2) was compared with the classical three-sample method (UKM3) and direct quantification. Assuming the patient to be in a weekly steady state and using an approximate treatment schedule, UKM2 can compute urea generation rate (G), distribution volume (V), Kt/V, and normalized protein catabolic rate (NPCR). Twenty-three stable patients were examined. The results obtained by UKM2 and UKM3 0.96). The differences between UKM2 and direct quantification were greater, but also highly correlated. G determined midweekly by UKM2 was highly correlated with G found directly from 1-week collection of dialysate and urine (r = 0.96). Repeating analysis over a 5-week period, the results obtained by UKM2 varied no more than those obtained by UKM3 (around 8% for all four kinetic variables). In conclusion, UKM2 produces reliable results requiring less data to be entered than using UKM3.

ISSN:1660-8151    

DOI:10.1159/000188359

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

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 follow: (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

ISSN:1660-8151    

DOI:10.1159/000188360

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effects of hormone stimulation on atrial natriuretic factor (ANF) release in atria were studied in experimental renal failure rats. In vitro experiments were done in two groups of male Wistar rats. Group 1 rats were sham operated, and group 2 rats were subjected to 5/6 nephrectomy. Overall glomerular filtration rate was significantly reduced (1.98 ± 0.10 vs. 0.75 ± 0.05 ml/min, p < 0.001) in nephrectomized rats. These rats were also mildly uremic [blood urea nitrogen (BUN): 18 ± 0.6 vs. 60+3.9 mg/dl p < 0.001]. The right atria of partially nephrectomized and sham-operated rats were isolated and perfused in a modified Langendorff apparatus to measure ANF release rate. Experiments were done in two phases. In the initial phase, spontaneous release of ANF was measured. In the second phase, angiötensin II (10-6M), vasopressin (10-6 M) or endothelin (ET 1; 10-6M) were added into the perfusate. Spontaneous ANF release by the atria of renal failure rats was significantly elevated compared to intact rats. A significant positive correlation was found between ANF release rate and BUN (r=0.65, p < 0.01). This suggests that the increase in ANF release by the atria of chronic renal failure (CRF) rats is related to the severity of renal impairment. Angiötensin II, vasopressin and endothelin induced exaggerated increases in ANF release by the atria of CRF rats. These results show that a shift in stimulus response curve is present and can contribute to the observed increase in plasma ANF levels in CRF

ISSN:1660-8151    

DOI:10.1159/000188361

出版商:S. Karger AG    

年代:1995

数据来源: Karger