ISSN:1660-8151    

DOI:10.1159/000190264

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Gene therapy is obviously a controversial issue and a wave of suspicion has dampened the initial enthusiasm raised by this new therapeutic approach. It has now become fashionable to downplay the potential for gene therapy in most fields including kidney-related diseases. In our opinion, this is an unfair and unrealistic view of the future. In fact, gene therapy of well-selected kidney diseases will certainly become feasible, but a large data base on vectors and transfer methods both in the normal kidney and in disease models has first to be collected. Any significant progress in the biology of the vectors, in the cellular interactions of the newly introduced DNA, and in the regulation and persistency of the transgene should be rapidly translated to the kidney in relevant experimental models. Herein, we present the use and current limitations of gene transfer to the kidney and the potential therapeutic perspectives.

ISSN:1660-8151    

DOI:10.1159/000190265

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The aim of this study was to assess the psychosocial effects of exercise training on hemodialysis (HD) patients. Thirty-one uremic patients, aged 50.6 ± 11.6 years, on maintenance HD were studied. Twenty patients were selected at random for a 6-month exercise renal rehabilitation program (ERRP) consisting of 3 weekly sessions of exercise training. The other 11 patients were assigned to sedentary control status. A formal psychosocial assessment, which included affective (Beck Depression Inventory, BDI), quality of life (Quality of Life Index, QLI) and personality (Eysenck Personality Questionnaire, EPQ) parameters, was performed with validated questionnaires at the beginning and the end of the ERRP. After training significant improvement occurred in physical capacity (VO2maχ increased from 16.8 ± 6.2 to 23.2 ± 7.6 ml/kg/min, p < 0.05). Although the level of depression did not differ betwen the 2 groups at pretesting, the ERRP group showed a decrease in their self-report of depression (decrease in BDI score value, from 21.0 ± 10.4 to 13.7 ± 9.5, p < 0.05) after the training program. From the relationship between the baseline levels of BDI depression and changes in VO2max in the ERRP group it was suggested that the most severely depressed patients got the greatest beneficial effects from exercise training. Moreover, trained patients demonstrated an improvement in QLI (from 6.3 ± 1.5 to 9.0 ± 0.9, p < 0.05). This improvement was found to be dependent on the participation in ERRP, the effects of the training and the improvement in the depression. All the above functional and psychosocial parameters remained unchanged in the controls. The results demonstrate that ERRP is an effective emotional therapeutic method for HD patients and improves their quality

ISSN:1660-8151    

DOI:10.1159/000190266

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The purpose of this study was to assess the feasibility of continuous ambulatory peritoneal dialysis (CAPD) after intra-abdominal prosthetic vascular graft surgery. We report 8 consecutive patients with end-stage renal disease, who previously underwent intra-abdominal prosthetic aortic graft replacement, treated by CAPD between November 1983 and November 1994. All patients received a peritoneal dialysis catheter without technical problems and were dialyzed for a total of 208 months. Six episodes of peritonitis occurred in 4 patients without clinical evidence of any abdominal aortic graft infection. Three patients developed intermittent claudication and 2 died of myocardial infarct. A similar peritonitis and cardiovascular complication rate was observed in a control group of age- and sex-matched CAPD patients with no aortic prosthesis. We conclude that CAPD is feasible in patients with abdominal aortic prosthesis.

ISSN:1660-8151    

DOI:10.1159/000190267

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The influence of angiotensin-converting enzyme inhibitors (ACEIs) on recombinant human erythropoietin (rhEPO) maintenance doses in hemodialysis patients was studied. One hundred and eight chronic hemodialysis patients (55 males and 53 females, mean age 61.2 ± 12.6 years) were investigated. The rhEPO maintenance doses in the ACEI-treated group (n = 49) were 101.7 ± 51.7 U/kg/week and in the nontreated group (n = 59) 79.2 ± 37.8 U/kg/week (p < 0.05). No difference was observed in hematocrit between the ACEI-treated and nontreated groups. In stepwise regression analysis, the parameters associated with increased rhEPO maintenance doses were female gender, ACEI administration, low total iron binding capacity, and low serum free carnitine levels. In conclusion, ACEI administration might reduce the response to rhEPO. In hemodialysis patients who need high-dose rhEPO to maintain the target hematocrit in the absence of iron deficiency, hyperparathyroidism, infection, malignancy, malnutrition, and aluminum toxicity, ACEI administration should be consider

ISSN:1660-8151    

DOI:10.1159/000190268

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Long-term therapy with recombinant human erythropoietin (rhEPO) in uremic male patients undergoing hemodialysis has been followed by an increase in plasma levels of testosterone and a decrease in baseline levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The aim of the present study was to assess the effect of acutely administered rhEPO on FSH and LH responses to gonadotropin-releasing hormone (GnRH) in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Sixteen clinically stable male patients (age, mean ± SEM, 45.3 ± 3.9 years) with chronic renal insufficiency and 12 healthy volunteers with a normal renal function, matched for age and body mass index, were studied. All patients were on CAPD therapy for at least 3 months, and none of them received rhEPO therapy. Patients were moderately anemic (hemoglobin 11.0 ± 0.3 g/dl) and showed testosterone levels significantly lower than those found in control subjects (3.47 ± 0.37 vs. 6.91 ± 0.49 ng/ml, p < 0.001). Each subject was tested with GnRH (100 μg i.v. as bolus) and with GnRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before GnRH injection) on different days. Blood samples for FSH and LH were obtained between -30 and 120 min. In uremic patients the baseline FSH levels were higher than those found in control subjects (18.88 ± 5.41 vs. 6.41 ± 1.10 mU/ml, p < 0.05). After GnRH administration FSH values reached a maximum of 25.50 ± 6.19 mU/ml in patients and of 12.50 ± 2.02 mU/ml in controls (p < 0.05). rhEPO infusion produced a significant (p < 0.01) decrease in the area above the baseline value of FSH in uremic patients, with no other change in FSH responses to GnRH both in patients and controls. Baseline LH concentrations were significantly higher in patients than in controls(15.56 ± 3.41 vs. 2.58 ± 0.36 mU/ml, p < 0.001). LH peak and area under the curve of LH secretion after GnRH were significantly higher in patients than in controls (45.25 ± 6.28 vs. 26.83 ± 4.62 mU/ml, p < 0.05, and 77.02 ± 11.30 vs. 34.40 ± 5.22 mU·h/ml, p < 0.005, respectively). When GnRH was injected during the rhEPO infusion, a significant (p < 0.02) reduction in LH concentrations at 60, 90, and 120 min was found in uremic patients. Accordingly, the LH area under the curve was significantly reduced in patients (65.99 ± 11.44 mU·h/ml, p < 0.05). rhEPO had no effect on GnRH-induced LH release in control subjects. These results suggest that acute rhEPO administration might reduce the exaggerated LH response to GnRH stimulation found in uremic mal

ISSN:1660-8151    

DOI:10.1159/000190269

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Therapy with human recombinant erythropoietin (EPO) has been accepted as effective for renal anemia in dialysis patients. However, studies in rats have shown that correcting anemia with EPO may affect the progression of renal dysfunction. In humans, however, the effect of EPO on residual renal function is a matter of controversy. We, therefore, investigated whether the long-term administration of EPO to predialysis patients influences residual renal function. Anemic patients at the predialysis stage with a serum creatinine (Cr) concentration ranging from 2 to 4 (average 2.9) mg/dl and a hematocrit (Ht) of less than 30% were randomly assigned to two groups which consisted of anemic patients not treated with EPO (group I, untreated anemic controls, n = 31) and anemic patients treated with EPO (group II, treated anemics, n = 42). Patients with nonsevere or moderate anemia (Ht > 30%) with a Cr ranging from 2 to 4 (average 2.6) mg/dl were also recruited as nonanemic controls (group III, untreated nonanemic controls, n = 35). Blood pressure was controlled to the same degree among the three groups by combined treatment with calcium antagonists and angiotensin-converting enzyme inhibitors. All patients were kept strictly on a low-protein (0.6 g/kg/day) and a low-salt (7 g/day) diet. The degree of control of dietary protein and blood pressure and the frequency of angiotensin-converting enzyme inhibitor administration were comparable among the three groups. The primary end point for each patient was a doubling of the baseline Cr which yielded cumulative renal survival rates which were plotted against time. Ht rose significantly from 27.0 ± 2.3 to 32.1 ± 3.2% in group II (n = 42, p < 0.001) with a rate of increase of 0.4 ± 0.06%/week. However, it declined from 27.9 ± 1.8 to 25.3 ± 1.9% in group I (n = 31, p < 0.001) and from 35.9 ± 3.5 to 32.2 ± 3.9% in group III (n = 35, p < 0.001). Cr doubled in 26 patients (84%) in group I as compared with 22 (52%) in group II and 21 (60%) in group III. The cumulative renal survival rates in groups II and III were significantly better than that in group I: p = 0.0003 (group I vs. group II) and p = 0.0024 (group I vs. group III). However, there was no difference in the renal survival rate between groups II and III (p = 0.3111). The better survival rate obtained in group II was attributable to the better survival rate for the nondiabetic patients in this group. The present study suggests that anemia, per se, is a factor in the progression of end-stage renal failure and that reversal of anemia by EPO can retard the progression of renal failure, especially in nondiabetic patiens, provided that blood pressure control, rate of increase in Ht, and dietary protein restriction are appro

ISSN:1660-8151    

DOI:10.1159/000190270

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We present our experience on the comparison of three different modes of steroid therapy, oral prednisolone (OP), intravenous dexamethasone (IVDX) and intravenous methylprednisolone (IVMP) in the treatment of acute rejection (AR) in renal allograft recipients. Between January 1980 and January 1992, 206 patients underwent live related renal transplantation. Before 1990, all received prednisolone (PRED) and azathioprine (AZA) only. After 1990, patients were given PRED, AZA and cyclosporine (CsA). After 1 year, CsA was stopped and patients were converted to a two-drug regimen only. Of the 206 patients, 180 (87.4%) were male and mean age was 30.3 ± 8.7 years (range 14-63). During the mean follow-up of 43.5 months, 178 episodes of AR were seen in 121 patients. Each episode was considered as a separate entrant in the study. Conventional immunosuppression was given in 151 episodes and 27 episodes were on triple-drug therapy. Diagnosis of AR was made by clinical, sonography, nuclear scan with or without graft biopsy evidence. Of the 178 AR, 110 (61.8%) were within 3 months, 36 (20.2%) were between 3 months and 1 year and 32 (18%) were after 1 year. OP was given in 11 cases while IVDX and IVMP were given in 48 and 119 cases respectively. Overall, 154 (86%) showed either a complete or partial response to antirejection therapy. Response to therapy was 91, 90 and 85% in OP, IVDX and IVMP groups respectively. There was no statistical difference in response rate in different groups. There was also no difference in side effects in three different groups. Our data suggest that it is the high dose of steroid rather than mode of therapy which is responsible for therapeutic benefit in treatment of AR

ISSN:1660-8151    

DOI:10.1159/000190271

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

There are very few data on the molecular biology of hepatitis C virus (HCV) infection in dialysis patients. 101 patients undergoing dialysis treatment in 4 units in the Lombardy, northern Italy, were analyzed by RT-PCR for HCV viremia, by line probe assay technology for HCV genotyping and by a serological analysis for detecting type-specific antibodies. 61 of 101 (60%) patients showed detectable HCV RNA in serum; HCV genotype 2a was dominant (30/ 53 = 57%), followed by HCV genotype lb (20/53 = 37%). There was no relationship between HCV genotyping and the clinical or demographic features of the patients. The antibody response toward the c33-c, cl00-3, and 5-1-1 antigens was more frequent in HCV genotype lb compared with genotype 2a (p = 0.046, p = 0.001 and p = 0.0001, respectively). The antibody levels to NS-3 and NS-4 HCV proteins were significantly higher in patients with HCV genotype lb in comparison with HCV 2a-infected individuals (p = 0.0001). There was a high level (82%) of agreement between HCV genotyping by RT-PCR and the assessment of type-specific antibodies by serological analysis; further, it was possible to detect type-specific antibodies in 6 of 22 (27%) patients in whom PCR amplification was unsuccessful. In conclusion, HCV subtype 2a was dominant in our population of HCV-infected dialysis patients, dialysis patients infected by different genotypes showed similar demographic and clinical characteristics, the antibody response toward the NS-3- and NS-4-related antigen of HCV was genotype dependent. There was a high level of agreement between HCV genotyping by RT-PCR and the detection of type-specific antibodies by serological analysis. As significant biological differences may exist among HCV strains, the assessment of HCV types may be very useful in the routine clinical activity of nephrologists in dialysis units.

ISSN:1660-8151    

DOI:10.1159/000190272

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Angiotensin II is a vasoactive peptide that has been widely implicated in the pathogenesis of glomerular disease. Some of its effects are thought to be independent of changes in blood pressure. Plasmin is a key regulator of fibrinolysis and extracellular matrix turnover. The conversion of plasminogen to plasmin by plasminogen activators (PAs) is controlled by their specific inhibitor, PAI-1. In this study we report the effects of angiotensin II on the production of PA inhibitor-1 (PAI-1) and tissue-type PA (t-PA) by glomerular mesangial cells in culture. Angiotensin II significantly increased the production of PAI-1 in the supernatant of mesangial cells (p < 0.05) in a dose-dependent manner, the maximum stimulation occurring at a concentration of 10-5M. The effect was not mediated by transforming growth factor-β (TGF-β), which is known to be induced by angiotensin II; TGF-β itself can increase PAI-1 expression. Angiotensin II did not alter t-PA production or incorporation of matrix fibronectin but did increase cellular proliferation and 3H-thymidine uptake. The increase in PAI-1 by angiotensin II may contribute to the persistence of fibrin deposits and extracellular matrix accumulation, providing another mechanism whereby angiotensin II contributes to glomerular dysfuncti

ISSN:1660-8151    

DOI:10.1159/000190273

出版商:S. Karger AG    

年代:1997

数据来源: Karger