ISSN:1660-8151    

DOI:10.1159/000188800

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

β2-Microglobulin-associated amyloidosis has emerged as a major complication of long-term renal replacement therapy. The syndrome is confined to those patients on nontransplant modes of therapy. It does not occur in patients with a functioning renal transplant or, if already present, it does not progress any further in such patients. In the population of ESRD patients on dialysis, β2-microglobulin-associated amyloidosis affects most patients treated for more than 15 years and is a cause of significant morbidity and in rare cases even mortality. The present review, which is based on the presentation of a typical case, discusses the current knowledge on the pathogenesis, clinical manifestations, diagnosis, prevention and therapy of β2-microblobulin-associated amyloidos

ISSN:1660-8151    

DOI:10.1159/000188801

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Uremic patients undergoing hemodialysis (HD) are known to be highly susceptible to infections. Recent data indicate that in addition to its well-known stimulating effects on red cell production, erythropoietin (EPO) may also have immunomodulating properties. The aim of this study was to examine the effect of EPO on lectin-induced T-lymphocyte transformation in uremic patients, as part of its effect on the immune response. Sixteen HD patients and 20 age- and sex-matched healthy controls were compared before and after 6 and 20 weeks of EPO treatment. T lymphocytes were analyzed for their mitogenic activity following treatment with phytohemagglutinin (PHA), concanavalin A (CON A) and anti-CD3 by measuring 3H-thymidine incorporation. HD patients showed reduced mitogenic responses to all mitogens tested, compared to healthy controls. During the 6 weeks of EPO administration, a significant increase in T-lymphocyte activity could be demonstrated following exposure to all three mitogens (PHA, from 32 ± 2 to 45 ± 8; CON A, from 11 ± 3 to 25 ± 9; anti-CD3, from 11 ± 3 to 22 ± 5, means ± SD). This increase was augmented after 5 months of EPO treatment. We conclude therefore that EPO improves in vitro T-cell mitogenic proliferation, even after short periods of tre

ISSN:1660-8151    

DOI:10.1159/000188802

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Recombinant human erythropoietin is widely used in chronic dialysis patients. However, the long-term effect, especially on the incidence of cardiovascular disease, has not been critically evaluated. We observed the annual incidence of stroke and acute myocardial infarction from April 1988 through March 1993 in Okinawa, Japan. Until April 1990, erythropoietin was not generally used. Therefore, we have two periods: pre-erythropoietin, April 1988 through March 1990, and post-erythropoietin, April 1990 through March 1993. Two thousand one hundred and sixteen patients (1,219 males and 897 females) were on chronic dialysis during the study period by March 31, 1993. Every case of stroke and acute myocardial infarction during the study period was registered. The odds ratio was calculated using the data of the general population in each sex and age class obtained in the same area. A total of 86 cases of stroke and 15 cases of acute myocardial infarction were registered during the study period. The annual incidence, per 1,000 patient-years, of stroke was 12.5 (1988), 10.5 (1989), 12.7 (1990), 14.0 (1991), and 17.5 (1992). The incidence of stroke was increased in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.22 and 95% confidence interval (95% CI 1.06-1.41, p < 0.01). The annual incidence of acute myocardial infarction was 1.0 (1988), 1.8 (1989), 0.8 (1990), 2.9 (1991) and 4.7 (1992). The incidence of acute myocardial infarction was increased significantly in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.87 (95% CI 1.66-2.10, p < 0.01). The odds ratio of stroke to the general population was 4.25 (95% CI 3.10-5.82) in the pre-erythropoietin and 4.58 (95% CI 2.14-9.80) in the post-erythropoietin period. In acute myocardial infarction, it was 2.98 (95% CI 2.84-3.12) and 3.81 (95% CI 3.18-4.56). The odds ratio of acute myocardial infarction was significantly increased (p < 0.01). The introduction of erythropoietin was associated with an increased risk of cardiovascular disease, especially acute myocardial infarction. Erythropoietin may unmask the sclerotic lesion in chronic dialysis patients.

ISSN:1660-8151    

DOI:10.1159/000188803

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The distinctiveness of IgM nephropathy (IgMN) as a clinicopathologic entity is controversial. Twenty-seven children (16 males, 11 females) with IgMN as defined immunohistochemically by diffuse mesangial staining of glomeruli for IgM were compared to a group of 63 children (40 males, 23 females) with minimal change disease (MCD). While mesangial expansion was significantly greater in IgMN than in MCD (p = 0.0014), there were no significant differences between the two groups with respect to the other biopsy factors. IgMN showed a significantly higher incidence of hypertension at presentation. More than 90% of patients in both groups presented with the nephrotic syndrome which in most initially responded to prednisone. Frequently relapsing/steroid-dependent nephrotic syndrome was the most common indication for biopsy in both groups. Approximately 60% of patients from both groups received cytotoxic therapy. Eight percent of IgMN and 7% of MCD patients failed to respond to therapy. Relapse rates and mean dose of prednisone at relapse were very similar in both groups prior to biopsy. Relapse rates diminished significantly after treatment in the postbiopsy interval, but mean dose of prednisone at relapse did not change appreciably over time. None of the patients developed renal failure or hypertension in the follow-up period. At last visit 23% of IgMN and 27% of MCD had proteinuria. The results indicate that IgMN and MCD are indistinguishable clinically in children who are biopsied for the nephrotic syndrome.

ISSN:1660-8151    

DOI:10.1159/000188804

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

To determine the cytokines responsible for the increase in production of IgA in patients with IgA nephropathy (IgAN), the roles of interleukin-4 (IL-4) and soluble CD23 (sCD23) were examined. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from 24 patients with IgAN and 14 patients with non-IgA proliferative glomerulonephritis. Twenty healthy adults served as controls. Concentrations of IgA and IgE in 10-day culture supernatants of PBMCs were measured by the sandwich ELISA method. Levels of sCD23 and activities of IL-4 in 4-day (96-hour) culture supernatants and serum were measured by ELISA and bioassay, respectively. Activities of IL-4 both in culture supernatants and serum were significantly elevated in patients with IgAN compared with controls (1.26 ± 0.53 vs. 0.68 ± 0.37 U/ml in culture supernatants, p < 0.05; 1.35 ± 1.34 vs. 0.89 ± 0.82 U/ml in serum, p < 0.05). Levels of sCD23 in IgAN patients’ serum were also significantly elevated (521.7 ± 514.9 vs. 173.0 ± 166.2 U/ml, p < 0.01). In vitro IgA and IgE synthesis were suppressed by anti-IL-4 monoclonal antibody (mAb) only when the antibody was added on the day when the culture was started (day 0). No suppression of IgA or IgE synthesis was observed when the antibody was added on day 4. IgE but not IgA synthesis was suppressed by anti-CD23 mAb when added on both days 0 and 4. Serum levels of IgE showed positive correlations with serum activities of IL-4 and with levels of serum sCD23. It is concluded that IL-4 and sCD23 might play decisive roles in in vitro and in vivo hyperproduction of IgA and IgE in patients with IgAN, and that sCD23 seemed to control IgE but not IgA synthesis through a unique

ISSN:1660-8151    

DOI:10.1159/000188805

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Phosphate binders are necessary to control hyperphosphataemia in the majority of dialysis patients. Whilst aluminium salts are efficient phosphate binders, their use is associated with toxic side effects. Calcium salts are a widely used alternative, but hypercalcaemia is a common side effect, limiting their use and raising concern about metastatic calcification. Reduction of the dialysis fluid calcium concentration has been shown to reduce hypercalcaemia in haemodialysis patients, with an associated decrease in serum PTH. We analysed the effect of reduced calcium/magnesium (1.25/0.25 mmol/l), 40 mmol/l lactate, PD fluid (PD4) on 11 CAPD patients with uncontrollable hypercalcaemia ( > 2.65 mmol/l) and hyperphosphataemia ( > 1.80 mmol/l). Only 1 patient remained hypercalcaemic, while phosphate fell in 6 patients (2.23 ± 0.16 on no binder, to 1.68 ± 0.08 mmol/l at 6 months (p < 0.05), but was unchanged in 5 (2.10 ± 0.15 to 2.48 ± 0.14 mmol/l [p = NS]). Overall mean calcium × phosphate product changed little. However, in a subgroup it fell significantly (p < 0.05). Geometric mean iPTH rose, but not significantly. The subgroup of patients whose calcium × phosphate product fell, exhibited a much smaller rise in iPTH than the others (57.3-73.2 vs. 52.8-167.1 pg/ml). 1.25-Dihydroxyvitamin D3 was subnormal in all patients. Mean serum magnesium fell from 1.24 ± 0.06 to 0.89 ± 0.04 mmol/l (p < 0.001), whilst mean serum bicarbonate rose significantly (25.2 ± 0.4 to 28.9 ± 1.2 mmol/l;p < 0.01). Withdrawal of aluminium-containing phosphate binders resulted in mean serum aluminium falling significantly from 31.1 ± 5.7 at start of PD4 to 15.4 ± 2.7 μg/l at 6 months (p < 0.05). In summary, in around 50% of CAPD patients with persistent hypercalcaemia and hyperphosphataemia, reduction in PD fluid calcium can produce significant improvement in phosphate, reduction of calcium × phosphate product, and enable avoidance of aluminium-containing phosphate binders. Patients whose calcium and phosphate control remains poor, still benefit from the reduction, or cessation, of oral alu

ISSN:1660-8151    

DOI:10.1159/000188806

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In rapidly growing male Sprague-Dawley rats with an initial body weight of 100 ± 10 g, we investigated how alimentary magnesium (Mg) supply, Mg metabolism and ciclosporine (Ci)-associated nephrotoxicity are interrelated. Food with 100 ppm Mg (lMg) or 1,000 ppm Mg (stMg) or 10,000 ppm Mg (rMg), Ci 20 mg/kg body weight daily or olive oil were applied for 3 months (n = 10/group). Mg concentrations in various compartments were measured by atomic absorption spectrophotometry. Creatinine clearance (Jaffé), urinary N-acetyl-β-D-glucosaminidase (NAG) activity (fiuorometrically), urinary sodium excretion (flame photometry) and osmolality were measured. Histomorphological examination was done and renal renin expression was studied by monoclonal antibodies. Ci reduced the Mg concentration of the femur under lMg(72.6 ± 9.7 vs. 112.6 ± 14.3 mmol/kg dry substance, p < 0.05) and under stMg (150.6 ± 16.6 vs. 194.1 ± 10.2 mmol/kg dry substance, p < 0.05), thus indicating Ci-related Mg deficiency. This was due to a significant increase in Mg excretion in Ci treatment compared to dietary controls. Under rMg, there was no difference between Ci-treated and control animals. Ci treatment lowered creatinine clearance in lMg (1.42 ± 0.05 vs. 3.02 ± 0.58 ml/min) and in stMg (1.04 ± 0.45 vs. 2.18 ± 0.51 ml/min), NAG/creatinine and urinary sodium excretion were negatively affected by Ci under lMg and stMg. Histomorphology showed macrocalcifications due to Mg deficiency and Ci-specifïc findings, which were markedly enhanced in lMg and stMg. Animals with plentiful Mg supply had no functional alterations due to Ci and no or weakly expressed histomorphological lesions. Renin-positive stained cells were higher in Ci-treated animals. This seems to be functionally relevant under lMg and stMg, since it was associated with sodium retention and elevated relative heart weight, indicating hypertension. Alimentary or drug-induced Mg deficiency plays a relevant role in the pathophysiology of chronic Ci nephrotoxicity. Our data suggest that Mg supplementation is helpful to reduce Ci toxicity, even if there is ‘normal’ alime

ISSN:1660-8151    

DOI:10.1159/000188807

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

There is evidence that fructose-1,6-diphosphate (FDP) provides protection from hepatic and cardiac toxic-induced damage and ischemic renal insult. To determine if FDP also protects against cyclosporine (CsA)-induced nephrotoxicity, two groups of adult male Wistar rats were studied for whole kidney clearance rates. After two initial control periods, group 1 received only CsA (CsA, n = 8). Group 2 received FDP 350 mg/kg, followed by CsA 50 mg/kg (FDP-CsA, n = 6). In both groups, after a 30-min equilibration period, two additional clearance rates were measured (Postl and Post2). A significant reduction in clearance rates was observed after drug infusion in both groups (approximately 58 and 64% in CsA and FDP-CsA groups, respectively, p < 0.05) with a recovery to control values in the Post2 period in the FDP-CsA group. These data suggest a protective effect of FDP on CsA-induced renal impairment.

ISSN:1660-8151    

DOI:10.1159/000188808

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

To clarify the pathogenesis of focal and segmental glomerulosclerosis, we investigated the effect of ovariectomy in hypercholesterolemic female Imai rats. At 5 weeks of age, control female (group 1) and control male rats (group 3) were sham-operated, female rats (group 2) were ovariectomized and male rats (group 4) were castrated. Body weight, blood pressure, urinary protein and serum constituents were checked every 2 months from 2 through 12 months of age. All groups were studied morphologically at 6 months of age and further female groups (1 and 2) studied at 12 months. Both control female and control male rats developed marked proteinuria, to a significantly greater extent in the male rats. Castration reduced proteinuria, while ovariectomy did not influence it and there were no significant differences in proteinuria among the control females, the ovariectomized females and the castrated males. Control male rats had significantly lower serum albumin levels, higher cholesterol levels and a significantly greater impairment of renal function in blood urea nitrogen (BUN) levels than did the control female rats at 6 months. Castration significantly increased serum albumin levels and lowered BUN levels, while ovariectomy did not basically influence these values in the female rats. The glomerulosclerosis index at 6 months of age was significantly higher in the control males than in the control females. Castration attenuated glomerular injury, while ovariectomy aggravated glomerular injury to the same levels as found in the castrated males. This aggravating effect of ovariectomy observed at 6 months, however, disappeared at 12 months. These results suggested that sex-related factors regulated by the ovaries may play an inhibitory role in the development of glomerulosclerosis before 6 months of age, but not thereafter, in hypercholesterolemic female Imai rats.

ISSN:1660-8151    

DOI:10.1159/000188809

出版商:S. Karger AG    

年代:1996

数据来源: Karger