摘要:

IgA nephropathy is the most common form of primary glomerulonephritis worldwide. About one quarter of patients progress to terminal renal failure 10 years after the apparent clinical onset. Therefore, the disease represents a social problem in terms of number of patients requiring maintenance hemodialysis. Despite the intense research effort devolved to clarify the pathogenesis of IgA nephropathy, the exact relationship linking the several factors involved is still unknown. In this review we analyze the experimental works reported since 1979, when the first animal model of IgA nephropathy was published by Rifai et al. We also discuss the interplay between experimental data and clinical observations to maximize the information gathered from the different animal models. Finally, we report the new insights into the role played by cytokines, growth factors and autacoids.

ISSN:1660-8151    

DOI:10.1159/000187084

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The expression of α2; α3; α5; α6-subunits of the β1 [very late activation (VLA)] integrin family was studied in kidney specimens using an immunofluorescent technique. 6 specimens from normal kidney were compared with 10 specimens from patients affected by various glomerulopathies [minimal change nephropathy (MCN), membranous nephropathy (MN) and systemic lupus erythematosus nephritis (SLEN)]. On normal glomeruli, α3 was the dominant integrin, being mainly present on podocytes and showing a linear fluorescent pattern codistributed with laminin. In MCN and SLEN, α3 presented a normal pattern. In MN, α3 revealed a trabecular picture on thickened glomerular basement membranes. Moreover, in stage-Ill MN, a segmental loss of α3-integrin was detected. In our opinion, VLA-3 may offer an interesting approach to the study of the relationships between podocytes and their s

ISSN:1660-8151    

DOI:10.1159/000187085

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Human cytomegalovirus (HCMV) has been suspected to participate in the pathogenesis of IgA nephropathy (IgAN). However, with regard to the presence of HCMV in the renal tissue of IgAN, conflicting results have been reported using a variety of different techniques. Renal biopsies of 29 patients with IgAN, of 7 with focal segmental glomerulosclerosis (FSGS) and of 11 normal kidneys were analyzed for the presence of HCMV-DNA using the polymerase chain reaction. HCMV-DNA was detected by hybridization with digoxigenin-labelled probes in 14 of 19 analyzed frozen renal biopsies from patients with IgAN. However, only 1 of 17 renal biopsies of IgAN embedded in paraffin was positive for HCMV-DNA. Furthermore, HCMV-DNA was detected in 4 of 18 frozen normal kidneys but in none of the tissues from patients with FSGS. The present results provide further evidence of an association between the presence of HCMV in renal tissue and IgAN.

ISSN:1660-8151    

DOI:10.1159/000187086

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

An increased incidence of hyperlipidemia places kidney graft recipients at increased risk for cardiovascular disease and may contribute to a decline in graft function. A study was undertaken to evaluate the safety and efficacy of lovastatin in these patients. Twelve kidney graft recipients with stable graft function and a cholesterol (chol) level over 250 mg/dl (6.46 mmol/l) were included. The lipid-lowering treatment consisted of 20 mg lovastatin daily, and all patients received immunosuppression with ciclosporin (CS) and prednisolone. Total chol decreased by 27% (300 ± 56 to 219 ± 28 mg/dl; 7.76 ± 1.45 to 5.66 ± 0.72 mmol/l; p < 0.01), LDL-chol by 35% (220 ± 38 to 143 ± 17 mg/dl; 5.69 ± 0.98 to 3.70 ± 0.44 mmol/l; p < 0.01) and triglycerides by 33% (207 ± 127 to 138 ± 56 mg/dl; 2.36 ± 1.44 to 1.57 ± 0.64 mmol/l; p < 0.05). HDL-chol increased by 10% (57 ± 11 to 63 ± 13 mg/dl; 1.47 ± 0.28 to 1.63 ± 0.34 mmol/l; NS). The ratio of total chol/HDL-chol, a generally accepted risk predictor of atherosclerosis, fell from 5.4 ± 1.3 to 3.3 ± 1.2, p < 0.01. Lipoprotein (a) [lp(a)], an independent risk predictor for atherosclerosis, was also evaluated at baseline and after 6 months of lovastatin treatment and showed a decrease of 39% (32.9 ± 27.6 to 19.9 ± 22.9 mg/dl; 0.85 ± 0.71 to 0.51 ± 0.59 mmol/l; p < 0.05). No adverse side effects were seen at this dosage, and hepatic and renal parameters remained unchanged. In conclusion, our data indicate that 20 mg of lovastatin daily is highly effective in correcting hypercholesterolemia in kidney transplant recipients and is accompanied by a sign

ISSN:1660-8151    

DOI:10.1159/000187087

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

IgG and IgA immune complexes, mononuclear phagocytic system function, interleukin-2 (IL-2) production by peripheral blood lymphocytes (PBL), serum-soluble IL-2 receptors, tumor necrosis factor, β2-microglobulin and IL-1β, HLA-DNA polymorphisms, immuno-isoelectrofocusing, phenotype of PBL, lymphocyte cytotoxicity, activation of lymphokine-activated killer cells and natural killer cell activity were evaluated in 8 patients with tubular/fibrillary glomerulonephritis (GN). No common serologic, immunologic or immunogenetic features suggestive of plasma cell dyscrasias were found. No elements to state whether these GNs represent a new entity or just atypical forms of known GN were foun

ISSN:1660-8151    

DOI:10.1159/000187088

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Hemodialysis patients have a capacity for extrarenal production of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]; however, the source of the hormone is unknown in these patients. Since 1,25(OH)2D3 synthesis by cultured hematopoietic cells has been demonstrated previously, we assessed hormone production by mononuclear cells from peripheral blood obtained from normal subjects (n = 6), uremic patients not yet requiring dialysis (n=4) and hemodialysis patients (n = 14). 1,25(OH)2D3 production was analyzed by sequential straight phase and reverse phase HPLC. In the hemodialysis group, the mean specific production of a metabolite co-eluting with 1,25(OH)2D3 (in fmol/100,000 cells/h) both by monocyte-enriched adherent cells (Mo) and lymphocyte-enriched non-adherent cells (Ly) was increased as compared to non-dialyzed subjects (119 vs. 22 for Mo, not significant, 65 vs. 14 for Ly, p < 0.05). Taken together, Mo and Ly from hemodialysis patients synthesized significantly more 1,25(OH)2D3 (p < 0.02) than non-dialyzed subjects (184 vs. 36, means). No differences were found between cells from normal subjects and patients with preterminal renal failure. Exposure of cultured normal Mo (n = 6) to cuprophane (CU), polyacrylonitrile (AN69) or polycarbonate-polyether (PC) membrane devices resulted in increased 1,25(OH)2D3 CU, whereby only PC (p < 0.05) was significantly different from control. Our results suggest that blood mononuclear cells contribute to extrarenal 1,25(OH)2D3 synthesis in hemodialysis patients, and that this synthetic activity may be related to the hemodialysis procedure

ISSN:1660-8151    

DOI:10.1159/000187089

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The purpose of the study was to determine the efficacy of furosemide in addition to intravenous fluids in the prevention of radiocontrast nephropathy. 18 patients, referred to a radiocontrast study, considered at risk because of preexisting renal insufficiency, were enrolled in a prospective, randomized, controlled trial, performed at the secondary care center of a 1,100-bed private university hospital. In addition to fluids, the treatment group received furosemide (mean dose 110 mg) intravenously 30 min prior to the injection of contrast material. The control group received fluids (mean 3 liters). Radiological studies were mostly angiographies performed with both ionic and non-ionic contrast material, at an average dose of 245 ml. Renal function significantly deteriorated in the group pretreated with furosemide (p < 0.005 by ANOVA), with a rise in serum creatinine from 145 ± 13 to 182 ± 16 μmol/l at 24 h, while no change occurred in the control group (from 141 ± 6 to 142 ± 7 μmol/l). Renal failure was associated with weight loss in the furosemide-treated group. Furosemide may be deleterious in the prevention of radiocontrast nephro

ISSN:1660-8151    

DOI:10.1159/000187090

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We have previously shown a significant increase in sulfate-35 uptake in rat glomerular basement membrane (GBM) when glomeruli were cultured with peripheral blood mononuclear cells (PBMC) from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse. In the present study, we have isolated the lymphokine mediating the augmented sulfate-35 incorporation and evaluated its effect on the catabolism of the GBM sulfated compounds. Supernatants from IMLNS PBMC cultures of 13 patients in relapse and 10 in remission were fractionated using gel filtration chromatography. There was a significant increase in rat GBM sulfate-35 uptake when glomeruli were cultured in carbonic anhydrase fraction from patients in relapse (12.9 ± 3.2; cpm/μg GBM protein, mean ± SEM) as compared to glomeruli cultured in the same fraction from patients in remission (8.2 ± 2.5: cpm/μg GBM protein; p < 0.05). The catabolism of the GBM sulfated compounds was determined by studying the washout of the sulfate-35 macromolecules after equilibration in sulfated isotope-free medium for 12 h. There was a significant decrease in residual sulfate-35 in rat GBM when glomeruli were cultured in a 29-kD fraction from patients in relapse (7.0 ± 2.5; cpm/μg GBM protein, mean ± SEM) as compared to glomeruli cultured in the same fraction from patients in remission (31.8 ± 1.6; p < 0.005). No significant differences in sulfate-35 incorporation were seen when other fractions from patients in relapse and in remission were compared. These studies suggest that the lymphokine secreted by PBMC from IMLNS patients in relapse increases the catabolism of the GBM sulfated compounds. This may cause a decrease in GBM net negative charge resulting in increased glomerular permeability to plasma

ISSN:1660-8151    

DOI:10.1159/000187091

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Bleeding due to impaired primary haemostasis is common in uraemia. However, thromboembolic episodes are also a clinical problem in dialysis patients. Platelet reactivity to shear stress (haemostasis, H1 and H2), exposure to collagen fibre (thrombus growth) and coagulation of flowing blood (clotting time, CT1 and CT2) were measured in non-anticoagulated blood samples taken immediately before and 18-24 h after haemodialysis (n = 26) and from patients maintained on continuous ambulatory peritoneal dialysis (CAPD, n = 30). H1 (p < 0.001), H2 (p < 0.01), percent thrombus growth rate (p < 0.03), CT1 (p < 0.01 and CT2 (p < 0.05) were restored towards normal after haemodialysis. Results obtained in the CAPD patients demonstrated that the mean values for formation of the haemostatic plug lay between the pre- and posthaemodialysis values; however, CT1 (p < 0.01) and CT2 (p < 0.05) were prolonged in CAPD compared with values after haemodialysis. These data, which indicate platelet function from non-anticoagulated blood and coagulation under flow conditions, (1) confirm that there is impaired haemostasis in uraemia; (2) demonstrate an improvement in haemostasis after haemodialysis; (3) show that peritoneal dialysis results in a haemostatic profile which falls between the pre-and posthaemodialysis pattern, and (4) show that neither dialysis modality returns haemostasis to normal.

ISSN:1660-8151    

DOI:10.1159/000187092

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Hypotension is a common problem in patients on hemodialysis. To further investigate this problem, the number of platelet α2-adrenoceptors and the activity of lymphomonocyte β2-adrenoceptors were measured in 10 hemodialyzed patients with normal blood pressure and in 10 sex- and age-matched persistently hypotensive hemodialyzed patients. Density of α2-adrenoceptors was assessed by the specific binding of 3H-yohimbine to intact platelets, while the function of β2-adrenoceptors was estimated by the production of cAMP after the exposure of lymphomonocytes to isoprenaline. The maximal number of α2-adrenoceptors was increased in the hypotensive compared to the normotensive group (262.13 vs. 77.21 fmol/mg protein; p < 0.01). Plasma norepinephrine was higher in the hypotensive than in the normotensive uremic patients (640 ± 195 vs. 344 ± 156 pg/ml; p < 0.01). Plasma epinephrine did not differ in the two groups (90 ± 30 vs. 94 ± 24 pg/ml). The amount of cAMP, produced by stimulation of lymphomonocytes, was lower in the hypotensive than that in the normotensive uremic patients (7.7 ± 2.4 vs. 15.6 ± 5.4 pmol/106 cells; p < 0.002). The increased number of α2-adrenoceptors together with a high level of norepinephrine and reduced activity of adenylate cyclase (coupled with β2-adrenoceptors) support the hypothesis that hypotension in the hemodialyzed uremic patients may be related to a defect in adrenoceptor couplin

ISSN:1660-8151    

DOI:10.1159/000187093

出版商:S. Karger AG    

年代:1992

数据来源: Karger