Immunoglobulin allotypes in patients in end-stage renal failure

In a population of 282 Caucasoid patients in end-stage renal failure (ESRF) Gm and Km typing has confirmed a significant increase in the frequency of the Gm1,2,17;21 haplotype. This was confined to an increase in the number of heterozygous Gm(1,2,3,17;21,5,10,13,14) individuals. A concomitant decrease in the frequency of presumptive Gm(3,5,10,13,14) heterozygotes was also confirmed. Analysis of individual renal diseases revealed significant immunoglobulin allotype, phenotype and haplotype frequency deviations in those patients presenting with hypertension, glomerulonephritis or pyelonephritis. The allotype distribution in patients with physical abnormalities of the urinary-genital tract, whether congenital or acquired, was normal.     

Hyperhomocysteinemia in end-stage renal failure

The end-stage renal disease (ESRD) population experiences an excess morbidity and mortality due to arteriosclerotic cardiovascular disease (CVD) outcomes. Specifically, event rates for myocardial infarction and stroke are 5- to 10-fold in ESRD patients on maintenance dialysis than in the general population. Recently, there is controlled evidence that hyperhomocysteinemia occurs more commonly than any of the traditional CVD risk factors in ESRD patients. Prolonged exposure of endothelial cells to homocysteine impairs the production of nitric oxide and endothelium-dependent vasodilatation, they combine with low-density lipoprotein cholesterol to produce aggregates that are taken up by vascular macrophages in the arterial intima (foam cells), produce aggregatory effects on the platelets, and decrease endothelial antithrombotic activity due to changes in the thrombomodulin function. Current treatment regimens for ESRD hyperhomocysteinemia, which are based on the pharmacological doses of folic acid (5 to 15 mg/day), frequently result in suboptimal lowering of Hcy concentrations. Other potential therapeutic approaches (such as oral N-acetylcysteine at 1.2 g/day) merit controlled investigation.     

Cystic renal changes in chronic hemodialysed patients

In this study we investigated the appearance of renal cysts in 43 chronic hemodialyzed patients using ultrasound (3.5 MHz-sector scanner). The mean age of the patients was 45 years, and the mean duration of dialysis was 26.3 months. In 21 patients (= 49%) cysts could be found. In 10 of these patients a former investigation at beginning of dialysis did not demonstrate any cystic lesions. The diameter of the cysts varied between 5 and 30 mm. Considering the duration of dialysis, in 9 (= 39%) out of 23 patients with a maximum duration of dialysis of 2 years cysts could be demonstrated by ultrasound, and in 12 (= 60%) of 20 patients, who had been dialysed for more than 2 years. The clinical impact of the demonstration of such cysts was recently reported in cases which developed complications like tumour formation or severe bleeding.     

维持性血液透析患者行冠状动脉搭桥术的临床分析

目的通过分析2例尿毒症维持性血液透析(HD)患者冠状动脉搭桥术(CABG)围手术期资料,探讨维持性血液透析患者行CABG的安全性。方法回顾性分析2例尿毒症维持性血液透析患者行冠状动脉搭桥术的临床资料。结果手术前一天均给予无肝素透析,术后均行持续床旁血液滤过透析(CHDF)。1例患者经完善的围手术期处理,手术成功,患者存活,生活质量明显改善;1例患者术后第3天于血液透析后死于心包填塞。结论维持性血液透析患者经过积极、周密的术前准备,术中及术后处理,可以接受冠状动脉搭桥术,可达到改善症状、提高生活质量、延长生命的目的。CHDF是慢性肾功能衰竭患者围手术期有效维持水、电解质平衡的透析方式。     

Alloantigen-stimulated induction and release of CD30 in patients with end-stage renal failure

High serum levels of soluble CD30 (sCD30) are associated with poor renal allograft survival, and regulatory T cells (Tregs) influence allograft survival depending on CD30 signaling. However, how sCD30 modulates alloimmune responses remains poorly understood. We measured the level of Tregs and sCD30 in patients with end-stage renal failure (ESRF) and analyzed whether allo- or polyclonal stimulation of the patients’ T cells results in the expression and release of CD30. ESRF patients showed increased serum sCD30 levels and lower percentages of circulating Tregs as compared to healthy controls (HC) (p < 0.001 and 0.024). Polyclonal and allogeneic stimulation resulted in higher expression of CD30, and after polyclonal stimulation, ESRF patients showed higher percentages of CD30-expressing T cells than HC (p < 0.001). Compared to autologous stimulation, allogeneic stimulation induced significantly higher expression of CD30 on T cells of ESRF patients only. After polyclonal as well as allogeneic stimulation, an increased sCD30 content was found in culture supernatants of both ESRF patients and HC (p < 0.001). Together with decreased Tregs, high serum sCD30 and increased induction of CD30 on T cells after polyclonal stimulation may explain exacerbated alloimmune responses and poor allograft survival in ESRF patients in whom immunosuppression is not able to control the alloimmune response.     

Protective and susceptible HLA polymorphisms in IgA nephropathy patients with end-stage renal failure

Idiopathic immunoglobulin A (IgA) nephropathy is characterised by an extreme variability in clinical course, leading to end-stage renal failure in 15-20% of adults. This subgroup of patients with IgA nephropathy is usually included in the waiting lists of organ exchange organisations. The frequency of HLA-A,B,DR antigens of this subset of IgA nephropathy patients was calculated and compared to controls. The antigens HLA-B35 and DR5 were significantly increased in the patients with relative risk values of 1.385 and 1.487, respectively. The antigens HLA-B7, B8, DR2, and DR3 were found in a significantly lower frequency in the patients as compared to the controls. The relative risk (RR) values ranged between 0.695 and 0.727. Consequently, the haplotypes HLA-A1, B8, DR3, HLA-A3, B7, DR2, HLA-A2, B7, DR2 together with HLA-A1, B15, DR4, HLA-A9, B12, DR7, and HLA-A10, B18, DR2 were found to be protective with RR values ranging from 0.309 to 0.587. The only susceptible haplotype observed was HLA-A2-B5, DR5 (RR=2.990).     

Serum vitamin E levels in patients with chronic renal failure

27 patients with chronic renal failure, 21 patients on chronic intermittent dialysis treatment and 27 healthy controls were tested for serum level of vitamin E estimated spectrophotometrically. Both patient groups had significant higher mean values (12.1 +/- 1.2 and 7.2 +/- 0.8 micrograms/ml respectively) in comparison with normal controls 4.6 +/- 0.7 micrograms/ml). No correlation was found to serum creatinine, hematologic values, protein and lipoprotein concentration, nor to mode and duration of treatment regimes. Vitamin E was not extracted from blood throughout dialysis. Under normal conditions of conservative or dialysis treatment of chronic renal failure patients vitamin E seems not to be a factor concerning uremic symptoms and there is no need for supplementation.     

Outcome of early initiation of peritoneal dialysis in patients with end-stage renal failure

Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone.     

Impact of long-term hemodialysis on nutritional status in patients with end-stage renal failure

We evaluated the way in which duration of hemodialysis treatment affects nutritional status in 96 end-stage renal failure patients. According to the length of previous hemodialysis treatment patients were divided into the groups: onset hemodialysis (ON-HD), early-stage hemodialysis (ES-HD, 1–8 months), mid-stage hemodialysis (MS-HD, 9–69 months), and advanced-stage hemodialysis (ASHD, 70–207 months). Nutritional status was assessed by laboratory data (serum proteins, total lymphocyte count), intradermal skin antigen testing, anthropometric measurements (body mass index [BMI], infrared interactance), and records of food intake. ON-HD patients on a low-protein diet exhibited abnormally low values for serum total protein, albumin, transferrin, and total lymphocyte count and a high prevalence of anergy to skin antigens (69%). In the ES-HD and MS-HD groups values for serum proteins and total lymphocyte count were in the normal range and significantly higher than in ON-HD patients. In addition, a lower proportion of cutaneous anergy was observed (50% and 27%, respectively). Long-term hemodialysis therapy for 6–17 years (AS-HD) was associated with normal levels for all measured serum proteins. Subnormal levels of total lymphocyte count, significantly lower than in MS-HD patients, were associated with an increase in anergy to skin antigens (46%). Serum prealbumin, complement C3c, BMI, body fat, and lean body mass exhibited normal values in all patients and showed no differences between groups. These results indicate that diminished visceral protein stores, lymphopenia, and anergy to skin antigens are widespread in undialyzed uremic patients with end-stage renal failure but become uncommon after the initiation of regular hemodialysis therapy. Even patients on long term hemodialysis for 6–17 years can maintain their serum protein levels, BMI, body fat, and lean body mass in the normal range. The catabolic stimulus of the dialysis procedure itself does not seem to outweigh its beneficial effect of removing uremic toxins when patients are treated for so many years. The occurrence of lymphopenia and a higher proportion of anergy to skin antigens in AS-HD patients indicates that hemodialysis treatment of very long duration has a depressive effect on immunological functions, but not on nutritional status.Abbreviations ON-HD onset hemodialysis - ES-HD earlystage hemodialysis - MS-HD mid-stage hemodialysis - AS-HD advanced-stage hemodialysis - BMI body mass index Correspondence to: P. Kaufmann     

Levels of vitamin D receptor and CYP24A1 in patients with end-stage renal disease

ObjectiveThis study was performed to detect the expression of vitamin D receptor (VDR) and cytochrome P450, family 24, subfamily A, polypeptide 1 (CYP24A1) in 24 end stage renal disease (ESRD) patients and 24 healthy controls.MethodIn this study, 24 ESRD patients and 24 healthy controls were included.ResultsIn our study, the levels of VDR in patients with ESRD were reduced when compared with those from healthy controls (5.20±0.32 vs 8.59±1.03; P<0.01). However, the levels of CYP24A1 in ESRD patients were increased than those from healthy controls (50.18±21 vs 7.78±1.31; P<0.01). Correlation analysis showed that VDR levels were negatively correlated with CYP24A1 (r=−0.723; P<0.01).ConclusionVDR levels were reduced and CYP24A1 levels were increased in patients with ESRD, and VDR levels were negatively correlated with CYP24A1.     

Serum vitamin B12 in renal failure

The serum vitamin B₁₂ level was abnormally high in 14 out of 32 cases of renal failure. This was probably due to impaired excretion of the vitamin, but the results of measurements of the rate of excretion of radioactive vitamin B₁₂ did not provide unequivocal evidence on this point; other possible explanations are discussed. Renal failure must be added to the causes of high serum B₁₂ levels.     

Von Willebrand factor and autoantibodies against oxidized LDL in hemodialysis patients treated with vitamin E-modified dialyzers

Oxidant stress is a well known cause of damage in the atherosclerotic process. Vitamin E is one of the most promising natural antioxidants. In this study we investigated if a vitamin E-coated dialyzer was able to reduce the plasma levels of auto-antibodies against oxidized-LDL, von Willebrand factor (vWf) and thrombomodulin (TM) as markers of endothelial damage. In this controlled 6-month prospective study, we investigated these markers in two matched groups (n=16 each) of patients on regular hemodialysis not yet diagnosed for atherosclerosis cardiovascular disease (ACVD) (mean age=58.3+/-7.0 yrs, mean dialysis age=30.1+/-10.0 months), in which cellulosic (CLS) and vitamin E-modified dialyzers (CLE) were compared. At inclusion all the patients were treated with CLS. Then, the study group was shifted to CLE for 6 months. At baseline the patients showed normal levels of vitamin E and high levels of oxLDL-Ab, vWf and TM compared to healthy subjects. In the CLE group oxLDL-Ab and vWf, but not TM levels, decreased progressively (from 472+/-287 to 264+/-199 mU/mL, p<0.0001 and from 101.1+/-7.5% to 76.7+/-18.5%; p<0.001, respectively), and vitamin E increased from 4.40+/-0.81 to 7.81+/-1.16 microg/mg of cholesterol. At the end of the study, 8 of the patients treated with CLE were randomly selected and went back to the membrane without Vitamin E for six months. They showed an significant increase in OxLDL-Ab and vWf levels and a significant reduction in tocoferol levels. In conclusion, CLE compared to cellulosic dialyzers can lower some indices of damage to LDL and endothelial cells.     

Oxidative stress on DNA in chronic renal failure: The influence of different hemodialysis membranes

It has been reported that uremia is a state of oxidative stress and may play an important role as a pathological cause of various uremic complications. Oxidative stress is known to increase conversion of deoxyguanosine to 8-hydroxy-2-deoxyguanosine (8-OHdG) in DNA, and 8-OHdG is used as a marker of oxidative DNA damage. We evaluated plasma and urinary concentrations of 8-OHdG in 49 patients (male 28, female 21; mean age 65 years; diabetic 27, nondiabetic 22) with chronic renal disease (CRD) and 22 patients (male 14, female 8; mean age 63 year; diabetic 7, nondiabetic 15) on maintenance hemodialysis (M-HD). Plasma concentrations of 8-OHdG were measured using a highly sensitive ELISA kit, and the urinary mean concentrations of 8-OHdG were measured using an ELISA kit. Plasma concentrations of creatinine (Cr), Urea nitrogen (UN), and β2-microgloblin (β2-MG) and 24-h creatinine clearance (CCr) were also measured in CRD patients. Furthermore, 8-OHdG was measured before the dialysis session in M-HD patients. The plasma concentration of 8-OHdG in patients on CRD was significantly correlated with serum-creatinine (S−Cr), serum-umea nitrogen (S-UN), and β-MG (P<0.0001) and also significantly negatively correlated with CCr (P<0.005), but was not significantly correlated with age, fasting blood suger (FBS), hemoglobin A1C (HbA1C), and urinary concentration of 8-OHdG were not correlated with S-Cr, S-UN, β2-MG, and CCr. The plasma mean concentrations of 8-OHdG in patients on CRD and M-HD were as follows: CRD (CCr>50 ml/min,n=12), 0.108±0.41 ng/ml; CRD (CCr<10 ml/min,n=9), 0.277±0.15 ng/ml; M-HD (n=22), 0.217±0.59 ng/ml (mean±SD). The mean plasma concentration of 8-OHdG was 0.296 ±0.75 ng/ml in patients on M-HD in the polysulfone mem-brane group, 0.304±0.122 ng/ml their cellulose membrane group, and 0.354±0.21 ng/ml their vitamin E-modified cellulose membrane group. This study showed that in CRD patients, oxidative stress on DNA increasesed with the progression of renal disease, and that end-stage CRD patients were already exposed to the same degree of oxidative stress on DNA as M-HD patients. In M-HD patients, oxidative stress on DNA was not related to the type of hemodialysis membrane.     

Oxidative stress, vitamin E and progestin breakthrough bleeding

Endometrial bleeding problems can be the major reason for discontinuing progestin-only contraception. In this study the endometrial angiogenic response in Norplant users was found to be lower than in women with normal menstrual cycles. These disturbances in angiogenic response may be caused by oxidant-antioxidant imbalance in the endometrium. The aims of this study were to investigate the effect of progestin only contraceptives on blood concentrations of lipid peroxide and vitamin E, and the effect of vitamin E supplementation on endometrial angiogenic response in vitro. The subjects for this study were Norplant users, depo-medroxyprogesterone acetate (DMPA) users, and controls. Circulating lipid peroxide and vitamin E concentration was measured by routine methodology. Endometrial angiogenic response was assayed using an endothelial cell migration assay. The results showed that the blood concentrations of lipid peroxide from Norplant users with bleeding problems were significantly higher than normal menstrual controls (P < 0.05) and supplementation of vitamin E (in vitro) increased the endometrial angiogenic score. Blood concentrations of lipid peroxide were significantly increased (P < 0.05), and the blood concentrations of vitamin E were significantly decreased (P < 0.05) after 3 months exposure to Norplant or DMPA. The endometrial angiogenic scores in Norplant and DMPA users were significantly lower than in controls (P < 0.02). It is concluded that in progestin-only contraceptive users, higher lipid peroxide and lower vitamin E concentration may cause endometrial cell damage and decrease the endometrial angiogenic response. It is suggested that vitamin E supplementation may counteract these unwanted side-effects.     

Oxidative stress and the muscle reflex in heart failure

Muscle contraction stimulates thin fibre muscle afferents and evokes a reflex increase in blood pressure. In heart failure (HF) this reflex is accentuated. Of note, superoxide and other reactive oxygen species are increased in HF. In this report, we tested the hypothesis that excess superoxide contributes to the exaggerated muscle reflex in HF. HF was induced in rats by coronary artery ligation. Electrically induced 30 s hindlimb muscle contraction in decerebrate rats with myocardial infarction (MI) (left ventricular fractional shortening (FS) = 24 ± 1%; n = 15) evoked larger ( P < 0.05) increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) as compared to control rats (FS = 47 ± 1%; n = 14). In the MI rats, the pressor and RSNA responses to contraction were reduced by intra-arterial injection into the hindlimb circulation of tempol (10 mg), a superoxide dismutase mimetic (ΔMAP: 22 ± 2 vs. 11 ± 1 mmHg; ∫ΔRSNA: 1032 ± 204 vs. 431 ± 73 arbitrary units (a.u.); before vs. after tempol; P < 0.05). Tempol also attenuated the RSNA response to 1 min intermittent (1–4 s stimulation to relaxation) bouts of static contraction in the MI rats (116 ± 17 vs. 72 ± 11 a.u.; P < 0.05; n = 16). In the control rats, tempol had no effect on these responses. These results suggest that excess superoxide in HF sensitizes mechanically sensitive muscle afferents engaged during contraction. We hypothesize that oxidative stress contributes to the exaggerated muscle reflex in HF.