糖尿病血液透析患者颈动脉粥样硬化、营养及微炎症状的关系

目的探讨糖尿病终末期肾病（ESDN）血液透析患者颈动脉粥样硬化（AS）与C-反应蛋白（CRP）的关系。方法检测28例原发于糖尿病及同期32例非糖尿病的维持性血液透析（MHD）患者一般临床指标、CRP水平,同时应用高分辨彩色B超检测患者颈动脉内膜-中层厚度（IMT）及粥样硬化斑块情况。结果原发于糖尿病患者尿素氮（BUN）、血浆白蛋白（Alb）、肱三头肌皮褶厚度（TSF）、上臂围（AC）、标准化蛋白分解率（nPCR）均显著低于非糖尿病的MHD患者;而血CRP、颈动脉IMT、颈动脉斑块阳性率、增厚阳性率显著高于非糖尿病的MHD患者;粥样斑块与CRP升高、高血压有关系。结论ESDN患者营养状况及低蛋白血症明显,血CRP水平高、AS明显而严重,AS可能与CRP及高血压有关,因此,改善营养状况、纠正微炎症状态,对治疗和预防ESDN患者AS有重要意义。     

Effects of folinic acid on forearm blood flow in patients with end-stage renal disease.

BACKGROUND: Abnormalities of endothelial function are likely to contribute to the accelerated atherosclerotic risk in subjects with end-stage renal disease (ESRD). While folates can improve endothelial function, their role in ESRD has not been fully studied. The objective was to determine the acute and 12 week-effect of folinic acid on endothelium-dependent vasodilation in subjects with ESRD. METHODS: Forearm blood flow (FBF) was assessed by strain gauge plethysmography at baseline and after 12 weeks in 34 ESRD patients (57 +/- 14 years). Vascular function was assessed with acetylcholine (ACh), and sodium nitroprusside (SNP). Patients were randomized to receive folinic acid (50 mg i.v. once weekly) or a matching placebo. A subset of 25 subjects also received folinic acid (500 microg/min intra-arterially) or placebo to determine the acute effect on ACh and SNP mediated dilation at the time of the baseline vascular study. RESULTS: Folinic acid acutely improved the maximum change in ACh mediated FBF (10.0 +/- 2.4 to 12.8 +/- 2.2 ml/min/100 ml, P = 0.017), but did not change SNP responses. Chronic active therapy did not change ACh or SNP-mediated increases in FBF. Folinic acid resulted in a non-significant decrease in homocysteine (21 +/- 6 vs 28 +/- 18 micromol/l, P = 0.16) and diastolic blood pressure was significantly reduced (P = 0.05). CONCLUSIONS: The present study demonstrated that folinic acid acutely improved endothelium-dependent vasodilatation in patients with ESRD suggesting a direct vascular effect. Chronic treatment with folinic acid did not show benefit in endothelial function, but did lower diastolic blood pressure. Further work is required to determine the optimal regime to protect vascular health in subjects with ESRD.     

Association of endothelial nitric oxide synthase gene intron 4 polymorphism with end-stage renal disease

BACKGROUND: Nitric oxide (NO) released from endothelial cells is related to the maintenance of physiological vascular tone. The impairment of endothelial NO generation brought about by gene polymorphism is considered one of the deterioration factors in progressive renal disease. In the endothelial nitric oxide synthase (eNOS) intron 4 polymorphism, the presence of the aa genotype has been associated with cardiovascular and renal disease. The aim of this study was to investigate the presence of eNOS gene intron 4 polymorphism in patients with end-stage renal disease (ESRD). METHODS: A total of 114 patients and 94 controls were studied. DNA specimens were extracted from blood and amplified by polymerase chain reaction. The alleles were separated by agarose gel electrophoresis. Genotype distribution and allele frequencies were compared between groups using the chi-squared test. RESULTS: Statistical analysis revealed that the frequency of the eNOS4 genotype aa was significantly different in ESRD patients and in controls (P=0.016, OR=2.07, CI 95%: 1.14-3.74). There was also a statistically significant difference between ESRD patients and controls regarding allele carriers (P=0.004; OR=2.26; CI 95%: 1.29-3.96). When the frequencies of allele carriers in the diabetic nephropathy group and in the control group were compared, a significant difference was found (P=0.034, OR=2.28; CI 95%: 1.04-5.00). CONCLUSION: This study showed a strong correlation between eNOS4a polymorphism and end-stage renal disease.     

Endothelial nitric oxide synthase gene intron 4 polymorphism in patients with end-stage renal disease.

BACKGROUND: Nitric oxide (NO) synthesized by endothelial cell NO synthase (ecNOS) is a potent regulator of intrarenal haemodynamics. A polymorphism in intron 4 of the ecNOS gene is a candidate gene in cardiovascular and renal diseases. We investigated a potential involvement of this polymorphism in chronic renal failure. METHODS: We performed a case-control study involving 706 patients with end-stage renal disease (ESRD) and 321 healthy controls. All subjects were genotyped for the ecNOS4 polymorphism by the polymerase chain reaction followed by agarose gel electrophoresis. RESULTS: The analysis revealed that the frequencies of the ecNOS4 genotypes were significantly different in ESRD patients, both diabetic and non-diabetic, than in controls. In all dialysis patients for aa, ab and bb genotypes the frequencies were, respectively, 6.5, 35 and 58.5% in the patient group, and 1, 25 and 74% in control subjects. The a allele carriers (aa + ab) were more frequent among ESRD patients than in controls (OR 1.95; 95% CI 1.13-3.4; P = 0.0031). No significant association was found when hypertensive ESRD patients were compared with normotensive patients. The distribution of genotypes was similar in both subgroups (P = 0.21). CONCLUSION: There was a significantly higher frequency of the ecNOS4a allele carriers among ESRD patients, both diabetic and non-diabetic, than in control subjects. This suggests that the ecNOS gene polymorphism may be associated with an increased risk of chronic renal failure.     

The adolescent with end-stage renal disease

The adolescent with ESRD is frequently immature in relationship to chronological age. Growth and pubertal development are major concerns for the adolescent with ESRD. If renal failure had its onset prior to adolescence, it is likely that puberty will be delayed and ultimate adult height retarded for the patient requiring ESRD care during the adolescent period. Non-compliance with the therapeutic regimen is a major clinical problem encountered in the management of the adolescent. Significant morbidity can result from non-compliance with the dialysis regimen and non-compliance is a major cause of allograft loss in the adolescent transplant recipient. The special needs of the adolescent must be considered if ESRD care is to be successful.     

Diabetic muscle infarction in end-stage renal disease.

BACKGROUND: Diabetic muscle infarction (DMI) is an unusual disorder of type 1 and type 2 diabetic patients with advanced microvascular damage including nephropathy. Few reports describe this complication among dialysis patients. METHODS: We studied four patients with terminal renal failure due to diabetic nephropathy who developed isolated skeletal muscle infarction at our institution between January 1998 and January 2003, and reviewed 15 additional cases of DMI reported among dialysis patients (Medline database search). RESULTS: Analysis of available data for all 19 cases revealed the following features: mean age at symptom onset of 46.4 years; average duration of renal replacement 25.7 months (range 36 h to 72 months); male predominance (2.2:1); higher prevalence of type 2 vs type 1 diabetes (2.2:1); and more common use of haemodialysis than peritoneal dialysis (2.6:1). One patient developed symptoms after being immobilized during surgery and initiating dialysis. Thigh involvement was frequent (17/19). Fever, leucocytosis and elevated serum creatine kinase levels were noted inconsistently, but were seen commonly with early evaluation after symptom onset. Erythrocyte-sedimentation rate and C-reactive protein levels were high when checked. All 16 instances of magnetic resonance imaging (MRI) demonstrated increased T2-weighted signal from affected muscles. Seven patients were managed without muscle biopsy. Histological features included myofibre necrosis (8/12), inflammatory infiltrates (8/12) and microvasculopathy (6/12). Symptoms resolved with conservative therapy, but patients were at high risk for subsequent infarctions of other muscles (14/19). CONCLUSIONS: DMI should be suspected in any diabetic dialysis patient who develops a painful, swollen muscle. A conservative MRI-based diagnostic approach may lead to satisfactory outcomes. The pathogenesis of the disorder is controversial, but the clinical sequence of one of our cases suggests precipitation by immobilization, direct pressure and/or haemoconcentration.     

Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy

Aims: Diabetic nephropathy (DN) is the major cause for end‐stage renal disease (ESRD) and the pathogenesis for DN developing into ESRD is not clear at present. Results from published studies on the relationship between angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and ESRD risk in DN patients are still conflicting. This meta‐analysis was performed to evaluate the association between ACE I/D gene polymorphism and ESRD risk in DN patients. Methods: Association studies were identified from the databases of PubMed, Embase and Cochrane Library on 1 October 2011, and eligible investigations were identified and synthesized using the meta‐analysis method. Results were expressed using odds ratios (OR) for dichotomous data and 95% confidence intervals (CI) were also calculated. Results: Twelve studies reporting the relation between ACE I/D gene polymorphism and ESRD risk in DN patients were identified. In overall populations, there was a notable association between D allele or DD genotype and ESRD susceptibility (D: OR = 1.32, 95% CI: 1.11–1.56, P = 0.002; DD: OR = 1.67, 95% CI: 1.25–2.21, P = 0.0004). In the sub‐group analysis according to ethnicity, D allele or DD genotype was associated with ESRD risk in Asians. In Caucasians, the association of DD genotype with ESRD risk was observed, but the D allele was not. Furthermore, ACE I/D gene polymorphism was associated with ESRD risk in patients with DN due to diabetes mellitus type 2, but the association was not found for patients with DN due to diabetes mellitus type‐1. Conclusions: Our results indicate that D allele or DD homozygous is associated with the ESRD susceptibility in DN patients. However, more investigations are required to further this association.     

Lack of association of angiotensin II type 1 receptor A1166C gene polymorphism with the risk of end-stage renal disease

Abstract

The association between angiotensin II type 1 receptor (AT1R) A 1166C (rs5186) gene polymorphism and end-stage renal disease (ESRD) risk remains controversial. We aimed to assess the association between AT1R A1166C gene polymorphism and ESRD susceptibility by performing a meta-analysis. Eligible studies were searched according to a predefined criterion using electronic databases. Eight articles were identified for the analysis of the association between AT1R A1166C gene polymorphism and ESRD risk. A allele and AA genotype were not associated with ESRD risk in overall populations, Caucasians and Asians (overall populations: p?=?0.834 and 0.832, Caucasians: p?=?0.853 and 0.884, Asians: p?=?0.243 and 0.982). CC and AC genotype were not associated with ESRD risk in overall populations, Caucasians and Asians (overall populations: p?=?0.304 and 0.712, Caucasians: p?=?0.510 and 0.987, Asians: p?=?0.319 and 0.225). In conclusion, AT1R A1166C gene polymorphism may not be correlated with ESRD risk in overall populations, Caucasians and Asians. However, more studies should be performed in the future.     

Association of apolipoprotein E gene polymorphism with end-stage renal disease and hyperlipidemia in patients on long-term hemodialysis

Background: Cardiovascular diseases (CVDs) are the leading cause of death of patients with chronic renal failure. Apolipoprotein E (apoE) plays an important role in the homeostasis of cholesterol and triglycerides. Objective: We aimed to investigate the possible link(s) between apoE gene polymorphism, inflammation and lipoproteins in hemodialysis patients. Methods: We studied 109 end-stage renal disease (ESRD) patients and 97 controls. The serum lipids, apolipoproteins, lipoprotein particles, high-sensitivity C-reactive protein (hs-CRP) and total homocysteine (t-Hcy) levels and paraoxonase (PON) activity were determined in our patients. We also analyzed apoE gene polymorphism in the patients and controls. Results: The analysis of the apoE gene demonstrated a predominance of the e3 allele in both the patients and controls, followed by the e4 and then the e2 alleles. The analysis of the apoE genotype and allele frequencies showed significantly higher e4 allele and E3E4 genotype frequencies and decreased e3 allele and E3E3 genotype frequencies in the patients compared with the controls. The e2, e4 and E3E4 carriers within the ESRD patient population presented an atherogenic lipid profile. However, there were no significant variations in the serum PON activity and the hs-CRP and t-Hcy levels between individuals with different apoE polymorphisms. Conclusions: Our findings suggest an association between the e4 allele, E3E4 genotype and ESRD. The apoE polymorphism affects the serum lipoprotein levels, and the ESRD patients who are e4 and e2 allele carriers are more likely to present an atherogenic lipoprotein profile that may be a major factor associated with increased risk of CVD.     

Angiotensin II type 1 receptor gene polymorphism in end-stage renal disease

The genes of the renin-angiotensin system (RAS) are involved in progression of renal failure. We examined the A1166C polymorphism at the angiotensin II type 1 (AT1R) locus in patients with end-stage renal disease (ESRD). The distribution of genotype and allele frequencies was compared in 430 dialysis patients and 260 healthy controls. DNA samples were amplified by the polymerase chain reaction (PCR) and amplification products were digested with BsuRI restriction enzyme. In the presence of cytosine (C) there is a restriction site for this enzyme, giving a fragment of 231 bp (C allele), whereas undigested 255 bp fragment indicates the presence of the A allele. The higher frequency of combined AC and CC genotypes was observed in the patient group than in controls (48.6 vs. 39.5%, p < 0.05). The average time from the onset of renal disease to ESRD in patients with C allele was significantly shorter than in those with AA genotype (6.3 vs. 13 years, p < 0.01). Positive family history of renal disease in patients with AC/CC genotype seems to increase this effect. Our results indicate that the presence of C allele of the AT1R locus polymorphism might be associated with faster deterioration of renal function.     

Impact of dialysis therapy on insulin resistance in end-stage renal disease: comparison of haemodialysis and continuous ambulatory peritoneal dialysis.

BACKGROUND: Insulin resistance contributes to the pathogenesis of atherosclerotic cardiovascular disease and, thus, has an important impact on the mortality of uraemic patients. Haemodialysis (HD) is known to improve insulin resistance observed in uraemia. However, it is not known whether continuous ambulatory peritoneal dialysis (CAPD) alleviates insulin resistance in adult uraemic patients. The objective of this study was to compare the effect of two different dialysis modalities, HD and CAPD, on insulin resistance in adult uraemic patients and to identify the possible predictive factors for changes in insulin resistance. METHODS: Insulin resistance was examined in 19 non-diabetic patients with end-stage renal disease (ESRD) before and after dialysis therapy (HD, n=10; CAPD, n=9), as well as in 10 healthy controls using the hyperinsulinaemic euglycaemic glucose clamp technique. The glucose disposal rate (GDR mg/kg/min) was used as an index of insulin sensitivity during the clamp technique. We also determined which of various biochemical parameters might be associated with change in insulin resistance by carrying out multiple logistic regression analysis. RESULTS: GDR was significantly lower (6.44+/-1.76) in ESRD subjects than in normal subjects (9.90+/-2.01). HD and CAPD therapies significantly normalized GDR from 6.53+/-1.84 to 9.74+/-2.88 and from 6.35+/-1.65 to 8.18+/-1.76 respectively. Multiple logistic regression analysis showed that changes in BUN, haematocrit and plasma bicarbonate were significant predictive factors for the change in insulin resistance. CONCLUSION: CAPD therapy, in spite of its possible adverse effects in patients with atherosclerotic disease, has been shown to improve insulin resistance in adult uraemic patients, similarly to HD therapy.     

Relationship between serum albumin level before initiating haemodialysis and angiographic severity of coronary atherosclerosis in end-stage renal disease patients.

BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.     

Association of endothelial nitric oxide synthase gene polymorphisms with end-stage renal disease: a systematic review and meta-analysis

Background and objective: Endothelial nitric oxide synthase (eNOS) is one of the potent regulators of intra renal hemodynamics. Polymorphisms of eNOS gene may be involved in the progression of renal disease, and may be the causative factors that contribute to the deterioration of renal functions. During the past decades, several studies investigated the association of eNOS polymorphisms with the risk of end-stage renal disease (ESRD), but the results remain unclear and the mechanisms are not defined. Our study was designed to examine the role of different eNOS genetic polymorphisms in the progression of ESRD. Materials and methods: Relevant studies were identified through PubMed, Embase, Medline and CNKI (China National Knowledge Infrastructure) database published between January 2000 and November 2013. The association between eNOS polymorphisms and ESRD susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CI) in fixed or random effects models. Results: Sixteen articles were identified for the analysis of association between eNOS gene polymorphisms and ESRD risk. A total of 2729 patients and 2190 controls for 4b/a, 851 patients and 1171 controls for G894T, and 513 patients and 487 controls for T786C were included in our analysis. Overall, 4a allele of 4b/a polymorphism produced a significant association in the global population (OR?=?1.47, 95% CI?=?1.05–2.06, p?=?0.03) in a random-effect model; T allele of G894T was also significantly associated with ESRD susceptibility in overall populations (OR?=?2.12, 95% CI?=?1.44–3.12, p?=?0.0001). Furthermore, 4a and T carriers were significantly associated with ESRD risk as well. No association was found between T786C polymorphism and ESRD. Conclusion: The evidence accumulated suggested that 4b/a and G894T polymorphisms in the eNOS gene were associated with ESRD susceptibility, indicating that 4a and T allele carriers might become significant genetic molecular markers for the onset of ESRD in overall populations. However, more studies should be performed in the further studies.     

Angiotensin-converting enzyme polymorphism gene and evolution of nephropathy to end-stage renal disease

Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of nephropathy and end-stage renal disease (ESRD). The association between angiotensin-converting enzyme (ACE) gene polymorphism and nephropathy evolution was studied. A random sample of 161 subjects from the Nephrology Department (of Hospital de Sant Pau) were divided into two groups: (i) 117 with end-stage renal disease; (ii) 44 with established nephropathy; and (iii) control groups of 129 subjects. The ACE gene polymorphism was performed by using polymerase chain reaction. High DD genotype presentation was observed in the two groups of subjects with nephropathy (46.12 and 61.37%, respectively vs 35.66% in controls; P < 0.0482), and also, a decrease was observed in the II genotype (6.4 and 4.54%, respectively vs 13.17% in controls, P < 0.0404). Glomerular filtration rate (GFR) was evaluated after 44 months of follow up. An important decrease of GFR was observed in patients with DD polymorphism versus other genotypes (initial, 32.3 +/- 7.9 and at 44 months, 18.35 +/- 3.3 mL/min vs 31.4 +/- 11.9 and 11.7 +/- 3.2 mL/min; P < 0.039). In a non-longitudinal study of patients in ESRD, patients with an ACE-DD genotype had a lower period of time between diagnosis of nephropathy and ESRD than patients with other genotypes (10.45 +/- 9.32 vs 19.5 +/- 8.4 years; P < 0.034). In conclusion, the ACE gene that controls RAS response may influence the development and progression of nephropathy to ESRD. Patients who develop several types of nephropathy have a higher risk of severe evolution if they have a profile of ACE-DD genotype.     

Apolipoprotein E gene polymorphism in renal transplant recipients: effects on lipid metabolism, atherosclerosis and allograft function

INTRODUCTION: Atherosclerosis is a serious complication and leading cause of mortality in renal transplant recipients (RTRs). Hyperlipidemia may be associated with progression of renal disease and chronic allograft dysfunction. Similarities in the pathogenesis of glomerulosclerosis and atherosclerosis have been proposed. Apolipoprotein (apo) E gene code forms three major isoforms (E2, E3, and E4) with variable effects on lipid metabolism. PATIENTS AND METHODS: A total of 118 patients, at a mean age of 40 +/- 8 yr, were included in the study. Apo E genotyping was carried out on genomic DNA using polymerase chain reaction and restriction enzyme. Carotid artery intima media thickness and atherosclerotic plaques were evaluated by B-mode ultrasonography. The plasma levels of lipids and lipoproteins and acute phase reactants were also studied. Allograft function was evaluated by measuring serum creatinine and creatinine clearance values. RESULTS: The frequencies of E2, E3, and E4 alleles were 0.10, 0.78, and 0.12 respectively. Carotid artery atherosclerosis was found in 25% of E2 carriers, 30% of E3 carriers, and 57% of E4 carriers. Total cholesterol, total triglyceride, low-density lipoprotein, very low-density lipoprotein, apo B 100 levels were found to be higher in apo E4 carriers. Median apo A1 level was higher and allograft functions were better in apo E2 carriers (p < 0.05). Multiple regression analysis showed that allograft functions were negatively correlated with elevated acute phase reactants (p < 0.01) and only the age, but not the apo E genotypes, was an independent risk factor for atherosclerotic vascular disease (p < 0.01). DISCUSSION: The pathogenetic events linking lipid metabolism and allograft functions and development of atherosclerosis are complex and multifactorial in RTRs. Our results showed that apo E genotypes have influences on lipids, lipoproteins and allograft functions. The ultimate role of apo E4 gene polymorphism as a risk factor for development and progression of atherosclerosis in RTRs should be sought in further studies.     

Duration of end-stage renal disease and kidney transplant outcome.

BACKGROUND: Patients nearing end-stage renal disease (ESRD) increasingly choose pre-emptive renal transplant (PRT) to avoid pre-transplant dialysis and to minimize ESRD. Compared with long-term dialysis, PRT has been shown to increase allograft survival. However, the merit of short-term dialysis is not well characterized, and it may be the better medical choice in some patients. The goal of the study was to characterize the relationship between the duration of dialysis vs allograft and patient survival. METHODS: We performed a retrospective nationwide cohort study of all kidney transplants (Tx) between January 1, 1990 and December 31, 1999, with a follow-up period through December 31, 2000. Participants were identified using the United States Renal Data System (USRDS), which tracks all ESRD cases in the nation including patients on dialysis and with kidney Tx. Patients with the history of more than one kidney Tx were excluded. Allograft survival and recipient survival were the primary outcomes of this study. Duration of ESRD as a continuous variable as well as divided into categories (14 days, 15-60 days, 61-180 days, 181-365 days, 1-2 years, 2-3 years, 3-5 years and >5 years) was the primary risk factor of interest. Models were adjusted for multiple donor and recipient factors, including demographics and co-morbidities, as well as for Tx procedure characteristics. RESULTS: A total of 81,130 patient records were used for analysis (age 44.1+/-14.3 years, 61% males, 24% black, 29% diabetic, pre-transplant ESRD duration 27.1+/-26.4 months, 26% living donors). ESRD duration, as a continuous variable, is associated with a modest increase in the risk of graft failure over time [hazard ratio (HR) 1.02 per year of ESRD duration, P<0.001]. When ESRD is studied as a categorical variable (duration of 0-14 days vs longer durations), the increased risk of allograft failure reached statistical significance only when the time on dialysis was > or =181 days. The duration of ESRD was a significant risk for recipient death (HR 1.04 per year, P<0.001); however, mortality risk reached statistical significance only when the patient had been on dialysis for > or =1 year. CONCLUSIONS: This study of USRDS records suggests that a short (<6 months) dialysis course has no detrimental effect on graft and patient survival, and should not be deferred if medically indicated.     

Association between oestrogen receptor alpha gene polymorphism and mortality in female end-stage renal disease patients.

BACKGROUND: In the general population, genetic variations in the oestrogen receptor alpha (ERalpha) gene may influence lipid abnormalities, cardiovascular disease (CVD), and mortality, but this has not previously been studied in end-stage renal disease (ESRD) patients. METHODS: A total of 227 ESRD (141 men and 86 women) patients starting renal replacement therapy (RRT) were genotyped for three ERalpha gene polymorphisms (Ser10Ser, PvuII and XbaI) and the associations between these polymorphisms and clinical and laboratory parameters and survival were analysed. Patients were followed for a median period of 55 months (range 1-126 months). RESULTS: The PvuII and XbaI polymorphisms were not associated with any of the clinical parameters. The ERalpha Ser10Ser CC genotype was present in 24 (28%) of the female and in 37 (26%) of the male patients. When comparing the CC genotype with the CT and TT genotypes, there were significant differences in lipid levels and inflammatory marker levels, especially in female patients. In female patients, the CC genotype was associated with lower prevalence of protein energy wasting (PEW) (17.4% vs 43.1%; P=0.03), lower median serum triglyceride (1.7 vs 2.1 mmol/l; P=0.001), higher median serum albumin (34.0 vs 32.5 g/l; P=0.03) and lower median high sensitivity-CRP (hsCRP) (2.2 vs 5.5 mg/l; P=0.03) levels compared with the CT plus TT genotypes. In male patients only HDL-cholesterol and ApoA levels were associated with this polymorphism. Whereas this polymorphism did not influence survival in males, the mortality was lower in female patients with the CC genotype (Kaplan-Meier; Log-rank 2.2, P=0.02). Moreover, female patients with the CT plus TT genotypes had a borderline significant increased relative risk (Cox hazard model; 6.6, 95% CI: 0.87-49.9 P=0.06) of death as compared with those with the CC genotype, even after adjustment for age and prevalence of CVD. CONCLUSIONS: Female, but not male ESRD patients with the ERalpha Ser10Ser CC genotype had lower prevalence of PEW, lower serum triglyceride, higher serum albumin and lower hsCRP levels. As this genotype was associated with a significantly decreased risk of all-cause death during the initial years of RRT, its protective properties need further study.     

终末期肾脏病腹膜透析患者的心血管疾病

目的 了解终末期肾脏病（ESRD）腹膜透析患者的心血管疾病（CVD）发病率和有关高发危险因素,以及并发CVD的腹膜透析患者治疗时需关注的问题。 方法 研究对象为上海交通大学医学院附属仁济医院慢性肾脏病（CKD）5期接受腹膜透析的患者,共254例入选,采用横断面回顾性调查分析方法。平均随访时间中位数为49个月。采集病史、血生化检测结果、腹膜透析充分性评估、颈动脉及心脏彩色多普勒超声检测结果。评估CVD事件的发生、发展和预后,以及进行相关因素分析。 结果 CVD事件发生率为37%（93/254）。发生CVD的患者多伴有糖尿病、透析龄较长、血三酰甘油水平较高、血清白蛋白较低、前白蛋白较低。彩色多普勒超声显示,发生CVD组的左房内径（LAD）（mm）、室间隔厚度（LVST）（mm）、左室心肌质量指数（LVMI）（g/m2）显著高于未发生CVD组（43.16±4.93比 38.02±4.77、11.19±2.05比10.01±1.45、中位数192.03比150.28,均P < 0.05）;颈动脉内膜中层厚度（IMT）较厚（中位数0.80比0.65）,颈动脉内径增宽;收缩期峰值流速（SPV）和舒张期峰值流速（DV）流速降低。既往无CVD的患者在随访过程中发生CVD时,其Ccr、Kt/V、D/Pr、理想体质量校正的蛋白分解率（nPCR）及血清白蛋白水平与无发生CVD组差异有统计学意义（P = 0.045、0.015、0.051、0.029及0.005）。在随访过程中出现新发CVD或CVD病情恶化的原有CVD的患者,都是透析龄较长以及三酰甘油水平较高者。LAD、LVST、LVMI及IMT在新发CVD和未发CVD两组间差异有统计学意义（P=0.033、0.022、0.045及0.029）。Kaplan-Meier生存分析显示,既往CVD史和CVD症状是生存的独立危险因素。血清白蛋白<330 g/L、LAD>39.6 mm及曾患腹膜炎的患者生存率较低。 结论 ESRD腹膜透析患者是CVD的高发群体,需了解这些患者的病史和伴随症状;保持透析的充分性;同时要防止腹膜炎的发生。     

New markers of accelerated atherosclerosis in end-stage renal disease

Over the last two decades, several studies have reported a high prevalence of cardiovascular disease in patients with end-stage renal disease (ESRD). This population usually presents both the traditional and non-traditional risk factors for atherosclerosis. Inflammation as well as impaired nitric oxide production are pivotal, throughout the whole process of development of atherosclerotic lesions from the very start. C-reactive protein (CRP), a marker of systemic inflammation and an independent predictor of cardiovascular mortality in the general population, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, are important risk factors for cardiovascular disease and mortality in the ESRD population. Increased CRP levels have been described in hemo-dialysis and peritoneal dialysis patients, probably due to concomitant diseases, recurrent infections and chronic dialytic therapy. CRP levels, however, are elevated even in predialysis patients, implying that factors related to uremia per se can promote CRP synthesis. Recent reports raise the question whether CRP could be more than just a sensitive marker of inflammation and may contribute actively to the development of the atherosclerotic lesion. ADMA accumulation in the ESRD population is a consequence of reduced renal excretion and impaired enzymatic degradation and is related to the progression of atherosclerosis. Both CRP and ADMA have been shown to be associated with increases in the incidence and progression of atherosclerotic lesions in carotid arteries, as evaluated by high-resolution Doppler ultrasonography.