Predictors of cardiovascular events in patients with end-stage renal disease: an analysis from the Fosinopril in dialysis study.

BACKGROUND: Cardiovascular events (CVE) are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. These patients are often excluded from CV clinical trials, and the prognostic factors associated with CVE in patients with ESRD have not been fully explored. A risk prediction model was created from the FOSIDIAL trial to identify factors predictive of CVE and to evaluate the relative strength of known predictors when considered together in a multivariate model. METHODS: FOSIDIAL was a prospective, randomized, double-blind study with 2-year follow-up and CVE adjudication. The study enrolled 397 patients with ESRD and left ventricular hypertrophy (LVH). CVE included cardiovascular death, non-fatal myocardial infarction, unstable angina, stroke, revascularization, heart failure hospitalization, resuscitated cardiac arrest and confirmed stroke. The model was built using a forward selection of all baseline variables. A structural equation model (SEM) was used to identify factors with an indirect association with CVE. RESULTS: CV history was the most important prognostic factor, followed by C-reactive protein (CRP), left ventricular mass index, diabetes and age. Smoking, low HDL, female gender and Kt/V were indirectly associated with CVE. CONCLUSION: Prior CV disease, elevated CRP, LVH, diabetes or advanced age identifies patients at the highest risk for CVE. These data may be useful to detect high risk patients, to define potential targets for pharmacologic intervention, and to plan future studies in ESRD. Further research is needed to identify effective approaches that reduce the rate of CVE in these patients.     

Prevalence and prediction of renal artery stenosis in patients with coronary and supraaortic artery atherosclerotic disease.

BACKGROUND: Renal atherosclerosis is associated with increased cardiovascular mortality. This study aimed to determine the prevalence and predictors of renal artery stenosis (RAS) in patients with coronary artery disease (CAD) and supraaortic arteries (SA) stenosis. METHODS: Renal angiography was performed in 1193 (807 men) consecutive patients referred for coronary or SA angiography. Group I included 296 (136 men, 60.1 +/- 9.5 years) patients with no significant (< 50%) lesion in coronary arteries or SA; group II included 706 (526 men, 62.2 +/- 9.7 years) patients with stenosis > or = 50% within single arterial territory (coronary arteries or SA) and group III included 191 (145 men, 64.9 +/- 8.5 years) patients with stenosis > or = 50% in both territories. RESULTS: Some RAS was found in 55 (18.6%) patients in group I, 250 (35.4%) patients in group II and 115 (60.2%) patients in group III (P < 0.001). The proportion of patients with RAS > or = 50% in groups I, II and III was 3.3, 6.2 and 18.3%, respectively (P < 0.001). RAS prevalence increased with the number of stenosed coronary arteries (38.4% in 1-vessel, 42.1% in 2-vessel, 48.5% in 3-vessel CAD, P < 0.001). Independent predictors of RAS > or = 50% identified by logistic regression analysis were SA stenosis [relative risk (RR) = 3.28, P < 0.001], 2-3-vessel-CAD (RR = 2.04, P = 0.002), creatinine level > or = 1.07 mg/dl (RR = 2.95, P < 0.001), hypertension (RR = 2.97, P = 0.012) and body mass index < 25 kg/m(2) (RR = 1.42, P = 0.169). A calculated score for RAS > or = 50% prediction (based on the regression model) was reliable (coefficient of determination, R = 0.978) and showed a sensitivity of 77.5% and a specificity of 63.9%. CONCLUSIONS: RAS prevalence and severity increases with the number of arterial territories involved and CAD severity. The following independent predictors of RAS > or = 50% were identified: SA involvement, 2-3-vessel-CAD, serum creatinine level and hypertension.     

Cardiovascular calcification in end-stage renal disease.

Cardiovascular diseases are common in patients with end-stage renal disease (ESRD) and cardiovascular morbidity and mortality among dialysis patients are substantially higher than in the general population. The reasons for this high incidence are multiple. They include traditional factors such as hypertension, diabetes, dyslipidaemia, sodium overload, and elevated homocysteine levels as well as disturbances of mineral metabolism, specifically abnormalities in phosphorus and calcium homeostasis. This review will describe the specific cardiovascular complications related to calcifications in ESRD, the implications of the abnormalities of mineral metabolism in its pathogenesis and the current imaging techniques available for the detection of cardiovascular calcifications. Excess of calcium load contributes to the development of cardiac calcifications; therefore, alternative strategies to diminish exogenous calcium load should be considered in patients with ESRD.     

Diabetes and coronary artery disease impose similar cardiovascular morbidity and mortality on renal transplant candidates.

BACKGROUND: In renal transplant candidates (RTC), diabetes and coronary artery disease (CAD) are commonly observed. However, whether diabetes imparts a cardiovascular risk equivalent to that of CAD and whether CAD adds to the cardiovascular risk associated with diabetes is unknown. METHODS: To assess the interplay between diabetes and CAD as a determinant of major adverse cardiovascular events (MACE), 288 high-risk RTC (56.4+/-8.1 years old, 72% males) underwent a comprehensive cardiovascular evaluation including coronary angiography. Patients were divided into four groups based on the diagnoses of diabetes and CAD (>70% narrowing), and followed up for 1-60 months (median, 17). The primary endpoint was the composite incidence of fatal/non-fatal MACE. RESULTS: During follow-up, 80 MACE occurred. Patients with diabetes (P=0.03) or CAD (P<0.0001) had a worse long-term prognosis. However, only in patients without diabetes was CAD associated with an increased incidence of MACE (10.6% vs 45.9%, P<0.0001). In patients with diabetes, the endpoints were not different between those with and without CAD. No difference occurred in the long-term prognosis of patients with diabetes (with or without CAD) and patients without diabetes with CAD. CONCLUSIONS: We concluded that in high-risk RTC, diabetes confers a cardiovascular risk comparable to that of CAD in patients without diabetes, independent of coronary obstruction. In patients with diabetes, concomitant CAD does not add to the already very high cardiovascular risk of this population.     

Prognostic value of stress myocardial perfusion imaging using adenosine triphosphate at the beginning of haemodialysis treatment in patients with end-stage renal disease

Background. Non-invasive detection of coronary artery disease(CAD) remains difficult in patients with end-stage renal disease(ESRD). This study evaluated the ability of pharmacologic stressmyocardial perfusion imaging to predict cardiac events in patientswith ESRD. Methods. A prospective study was carried out in 49 consecutivepatients with ESRD. Thallium-201 single photon emission computedtomography (SPECT) using high-dose adenosine triphosphate (ATP)was performed within 1 month of the beginning of haemodialysis.The study end-point was a cardiac event or the 1-year anniversaryof the SPECT study. Results. Twenty-four patients (17 diabetics, 57% and seven non-diabetics,37%) had myocardial perfusion defects. The remaining 25 patientshad normal perfusion images. Fifteen patients had non-fatalcardiac events and two patients died of a cardiac cause. Allpatients who had non-fatal cardiac events underwent myocardialrevascularization and survived until the end of follow-up. The1-year cardiac event-free survival rate was 34% among patientswith perfusion defects and 96% among patients without perfusiondefects (P<0.001). The presence of a myocardial perfusiondefect was the only independent predictor of 1-year cardiacevents both in overall (HR, 49.91; 95% CI, 5.15–484.00;P<0.001) and in diabetic patients (HR, 33.72; 95% CI, 2.96–383.5;P = 0.005). Diabetes and an increased C-reactive protein wereassociated with the progression of CAD. Conclusions. Normal myocardial perfusion imaging by stress thallium-201SPECT using high-dose ATP performed within 1 month after thebeginning of haemodialysis treatment is a powerful predictorof cardiac event-free survival in patients with ESRD.     

终末期肾脏病透析患者骨密度与冠脉钙化的相关性分析

目的探讨终末期肾脏病(end stage renal disease,ESRD)透析患者骨密度与冠状动脉钙化(coronary artery colcification,CAC)之间的相关性。方法本研究为横断面研究。纳入115例ESRD患者,收集相关人口学特征、原发病、实验室检查等资料,双能X射线评估腰椎、股骨颈及髋部骨密度,多层螺旋计算机断层扫描(MSCT)检查患者CAC发生情况。以钙化积分100为界,将患者分为高钙化组和低钙化组。结果高钙化组56例,占维持性透析患者48%,其中男性36例,占高钙化组人数64.3%。高钙化组年龄、透析龄及血清甲状旁腺激素、碱性磷酸酶、25(OH) D水平均明显高于低钙化组,而股骨颈骨密度、髋部骨密度、血清胆固醇水平明显低于低钙化组(P0.05);男性高钙化组股骨颈骨密度及髋部骨密度明显低于低钙化组,且其冠脉钙化积分与股骨颈骨密度(r=-0.34,P0.05)、髋部骨密度(r=-0.65,P0.01)呈负相关。多元线性回归分析校正了年龄、透析龄等因素后仍显示男性髋部骨密度与冠脉钙化积分呈负相关(β=-1870.47,P0.05)。但在女性患者中,高钙化组与低钙化组骨密度无明显差异。结论骨密度降低可能是男性维持性透析患者冠脉钙化风险增高的危险因素。     

Critical limb ischaemia as a main cause of death in patients with end-stage renal disease: a single-centre study.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a high overall mortality rate, particularly due to cardiovascular morbidity. In an era of decline in cardiovascular diseases and early cardiovascular intervention, non-cardiac diseases seem to have a larger impact on overall mortality. METHODS: From 1997 to 2003, all incident haemodialysis patients in a single centre were enrolled in this prospective study. Those with clinical signs of vascular disease were examined by coronary or peripheral angiographies. Physicians took the patients' medical histories, examined them and followed them up until the end of the study or death. Causes of death were defined by the physicians. RESULTS: In all, 322 patients were enrolled in the study, 38% of whom were diabetic. At the start of dialysis treatment, 38% had coronary artery disease (CAD), defined as >50% stenosis of at least one coronary artery or as definite myocardial infarction, and 14% had critical ischaemia of at least one limb (CLI). In all patients with foot lesions, CLI was defined angiographically, as evidenced by stenosis or rarefication of distal vessels in the legs. Patients who died (n = 121) [due to cardiac causes (n = 25), complications of CLI (n = 22), stroke (n = 10), cachexia following a long-standing, non-malignant disease (n = 6), malignancy (n = 24), infection not related to CLI (n = 18) and other causes (n = 16)] were older (71+/-10 vs 65+/-13 years), more often male [74/121 (61%)] and often diabetic [56/121 (46%)]. CAD was documented in 82/121 (68%). Five-year survivals in patients with no risk and diabetes without CAD or CLI, CAD and CLI were 74%, 73%, 50% and 10%, respectively. Age, CLI and smoking habits independently increased the risk of death (hazard ratios: 1.052, 4.921 and 2.292, respectively). CONCLUSIONS: These results indicate that CLI with associated complications is not only an indicator of high mortality in patients with ESRD, but is also one of the main causes of death.     

冠状动脉瘤样扩张与弥漫性扩张的血管造影特征及心血管危险因素

目的比较冠状动脉瘤样扩张(CAA)与弥漫性扩张(CAE)血管造影特征及心血管危险因素的差异。方法回顾性分析16 778例冠状动脉造影图像。结果 211例存在冠状动脉扩张,包括132例CAA、79例CAE。CAA发病率、合并冠状动脉疾病发生率及其Gensini评分均明显高于CAE(P均0.05);CAA患者冠状动脉血管平均直径小于CAE (P0.05),心肌梗死溶栓(TIMI)血流分级均低于CAE(P均0.05)。血脂异常、吸烟及冠状动脉病家族史为CAA的独立危险因素(P均0.05)。结论 CAA与CAE在血管造影特征及心血管危险因素方面存在显著差异。     

Soluble adhesion molecules in end-stage renal disease: a predictor of outcome.

BACKGROUND: Inflammation is thought to contribute to initiation and aggravation of atherosclerosis through a process predominantly mediated by adhesion molecules. The aims of this study were to investigate the association between the concentrations of circulating soluble intercellular (sICAM-1) and vascular cellular (sVCAM-1) adhesion molecules and clinical outcome, and to evaluate the effect of antihypertensive drugs on sICAM-1 and sVCAM-1 concentrations in end-stage renal disease (ESRD) patients. METHODS: We prospectively investigated 310 (191 males) incident ESRD patients, 53+/-12 years old, shortly before the start of renal replacement therapy. Glomerular filtration rate (GFR) was 6.4 (range 0.8-16.5) ml/min/1.73 m(2). Plasma sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) kits. Survival was determined from the day of examination, with a mean follow-up period of 39 (range 1-123) months. RESULTS: In non-adjusted analysis, high sICAM-1 and sVCAM-1 levels were associated with all-cause and cardiovascular (P<0.001) mortality. After adjusting for age, gender, diabetes mellitus, serum cholesterol, C-reactive protein (CRP), subjective global assessment and angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB), the association between high sICAM-1 and mortality remained significant for all-cause (HR 1.9; CI 1.2-2.9, P = 0.004) and cardiovascular (HR 1.8; CI 1.1-3.1, P = 0.02) mortality, and a high sVCAM-1 was associated with all-cause mortality (HR 1.7; CI 1.04-2.7, P = 0.03). Furthermore, the concentration of sICAM-1, but not sVCAM-1, was lower in patients receiving ACEI/ARB (254+/-83 vs 275+/-92 ng/ml; P<0.05) or patients receiving calcium channel blockers (CCB, 251+/-75 vs 273+/-95 ng/ml; P<0.05) than in non-users. CONCLUSIONS: In ESRD patients, sICAM-1 and sVCAM-1 are independent predictors of all cause and cardiovascular death. The use of ACEI/ARB or CCB was associated with decreased concentrations of soluble adhesion molecules.     

Risks of coronary artery bypass surgery in dialysis-dependent patients--analysis of the 2001 National Inpatient Sample.

BACKGROUND: Dialysis patients have a high risk of cardiovascular death but may under-use coronary artery bypass grafting (CABG) because of the risk of peri-operative death. Whether operative mortality in dialysis patients has declined with contemporary techniques is uncertain. We undertook this study in order to compare peri-operative mortality in chronic dialysis (CD) and non-dialysis patients following CABG and to determine whether high levels of comorbidity in CD patients account for identified differences in operative risk. METHODS: This study is a retrospective analysis of the 2001 National Inpatient Sample, a stratified probability sample of over seven million admissions in 33 states. Administrative data and ICD-9CM codes were used to identify dialysis patients, comorbidities, procedures and operative outcomes. Multivariable logistic regression was used to adjust for confounding. RESULTS: In this study, 77 323 non-dialysis patients and 635 dialysis patients underwent CABG. In-hospital death occurred in 11.1% of dialysis patients compared to 3.4% of non-dialysis patients. Rates of stroke, sepsis and pneumonia were also increased in dialysis patients. After adjustment for other surgical risk factors, the odds of in-hospital death were 3.38 (2.54-4.50, P < 0.001) times higher in dialysis than non-dialysis patients. CONCLUSIONS: Operative mortality in dialysis patients remains high despite recent advances in CABG surgery and is not explained by the high rates of comorbidity in dialysis patients. Because there is a very high risk of cardiovascular death without intervention, CABG may nevertheless be a life-saving therapy in CD patients. Randomized trials are needed to better define the optimal role of CABG in dialysis patients.     

Effect of anaemia on mortality, cardiovascular hospitalizations and end-stage renal disease among patients with chronic kidney disease

Objective:   To determine whether an independent association exists between anaemia and chronic kidney disease (CKD) outcomes in a quasi-incidence cohort when patients' most recent laboratory values are considered.
Methods:   We conducted a dynamic, retrospective cohort study among patients with incident CKD in a large health maintenance organization administrative data set. CKD was defined by two estimated glomerular filtration rates (eGFR). We measured the absolute rates for all-cause mortality, cardiovascular hospitalizations and end-stage renal disease.
Results:   Our completed cases Cox regression model followed 5885 patients with both CKD and haemoglobin measures. For patients with the most severe anaemia (haemoglobin <10.5 g/dL), we estimated an increased rate of mortality (hazard ratio (HR) = 5.27, CI 4.37–6.35), cardiovascular hospitalizations (HR = 2.18, CI 1.76–2.70) and end-stage renal disease (HR = 5.46, CI 3.38–8.82) when compared with patients who were not anaemic; the HR reflect time-varying haemoglobins and eGFR.
Conclusion:   Anaemia is a predictor of excess mortality, excess cardiovascular hospitalizations and excess end-stage renal disease even when the progression of CKD is considered by controlling for time-varying eGFR values.     

Late nephrology referral and mortality among patients with end-stage renal disease: a propensity score analysis.

BACKGROUND: Late nephrology referral has been associated with adverse outcomes among patients with end-stage renal disease; however, its relationship to mortality is unclear. We examined the impact of timing of nephrology care relative to initiation of dialysis on mortality after initiation of dialysis. METHODS: Data from the Dialysis Morbidity and Mortality Study - Wave II, a prospective study of incident dialysis patients, were used. Late referral (LR) was defined as first nephrology visit <4 months and early referral (ER) as first nephrology visit >or=4 months prior to initiation of dialysis. Propensity scores (PS) were estimated using logistic regression to predict the probability that a given patient was LR. A Cox proportional hazards model was built to examine the association between timing of nephrology referral and mortality. RESULTS: The cohort was comprised of 2195 patients: 54% were males, 66% were Caucasians, 26% were African-Americans and 33% were referred late. A Cox proportional hazards analysis demonstrated that compared with ER patients, LR patients had a 44% higher risk of death at 1 year after initiation of dialysis [hazards ratio (HR) = 1.44; 95% confidence interval (CI): 1.15-1.80], which remained significant after adjusting for quintiles of PS (HR = 1.42; 95% CI: 1.12-1.80). CONCLUSIONS: Among patients with chronic kidney disease (CKD) who initiated dialysis, LR was associated with higher risk of death at 1 year after initiation of dialysis compared with ER.     

Seropositivity for cytomegalovirus in patients with end-stage renal disease is strongly associated with atherosclerotic disease.

BACKGROUND: Infection with cytomegalovirus (CMV) is considered a risk factor for progression of atherosclerotic disease. Patients with end-stage renal disease (ESRD) display signs of frequent CMV re-activation, which may be caused by the uraemia-associated defect in cellular immunity. The possible contribution of CMV seropositivity to the hugely increased risk for cardiovascular disease in patients with ESRD is not clear. METHODS: In a retrospective study we analysed the clinical data of patients with ESRD that were evaluated for renal transplantation from January 2002 to March 2006. Classical cardiovascular risk factors and CMV seropositivity were related to the prevalence of atherosclerotic disease. RESULTS: A total of 408 patients were evaluated with a median age of 52 years (range 18-81 years). Multivariate logistic regression identified age (odds ratio; OR 2.7 per decade), smoking (OR 2.2), hypertension (OR 1.9), C-reactive protein (CRP) (OR 2.6) and CMV seropositivity (OR 2.7) as independent variables that were significantly associated with a positive medical history of atherosclerotic disease. The average titre for anti-CMV immunoglobulin G was higher in patients with atherosclerotic disease (100 AU/ml vs 71 AU/ml, P < 0.05). CMV seropositivity was independently associated with an elevated CRP. In addition, patients with the combination of a high CRP and CMV seropositivity showed the highest prevalence of atherosclerotic disease. CONCLUSION: CMV seropositivity is significantly associated with atherosclerotic disease in ESRD patients. Our data suggest that the risk for progressive atherosclerosis is specifically increased in patients with an inflammatory response to CMV.     

Removal of clodronate by haemodialysis in end-stage renal disease patients

BACKGROUND: Clodronate is a potent calcium-lowering drug. The effect ofhaemodialysis on clodronate pharm-acokinetics is unknown. METHODS: The removal of clodronate by haemodialysis was determined in10 end-stage renal disease patients (ESRD). A 2-h infusion of300 mg of clodronate was followed immediately by a 4-h haemodialysis.Vascular access was by AV fistula. A 1.5-m² cuprophane hollow-fibredialyser was applied. Blood flow was 205±15ml/min, dialysateflow 523±29 ml/min. Clodronate was determined by high-performanceliquid chromatography in total collected dialysate, and in bloodbefore and after the dialyser at initiation, 2 h, and 4 h ofHD. RESULTS: The initial predialyser serum concentration of clodronate was13.6 ± 4 ug/ml. It decreased to 4.9 ± 0.5 ug/mland 2.6 ± 0.5 ug/ml at 2h and 4h respectively. The clearanceof clodronate (86 ± 10 ml/min) remained unchanged duringHD. Clodronate in total collected dialysate per single 4-h HDwas 105 ± 16 mg (35% of injected dose). CONCLUSIONS: We conclude that clodronate is effectively removed from plasmaby HD. The present data together with information provided byprevious studies suggest that 300 mg of clodronate given asan 2-h infusion immediately prior to haemodialysis is an adequatedosage for ESRD patients.     

Unilateral renal cell carcinoma with coexistent renal disease: a rare cause of end-stage renal disease.

BACKGROUND: Renal cell carcinoma (RCC) is a disorder encompassing a wide spectrum of pathological renal lesions. Coexistence of unilateral RCC and associated pathology in the contralateral kidney is an unusual and challenging therapeutic dilemma that can result in renal failure. So far, data on unilateral RCC with chronic renal failure necessitating renal replacement therapy have not been published. The aim of the present study was to evaluate the incidence of end-stage renal disease (ESRD) from unilateral RCC, and to assess the associated pathology and possible pathogenic factors. METHODS: In 1999, a survey of the 350 patients treated by chronic dialysis in Asturias, Spain, was carried out to identify and collect clinical information on patients with primary unilateral RCC whilst on their renal replacement programme. RESULTS: Seven patients were identified as having ESRD and unilateral RCC, giving an incidence of 2% of patients treated by dialysis. There was a wide spectrum of associated disease and clinical presentation. All patients underwent radical or partial nephrectomy and were free of recurrence 6--64 months after surgery. Six patients were alive and free of malignancy recurrence for 6--30 months after the onset of haemodialysis. CONCLUSION: ESRD is rare in association with unilateral RCC, but does contribute to significant morbidity. However, the data presented here are encouraging and suggest that cancer-free survival with renal replacement therapy can be achieved in such patients.     

Long-term impact of renal transplantation on carotid artery properties and on ventricular hypertrophy in end-stage renal failure patients.

BACKGROUND: The aim of this study was to examine prospectively the impact of renal transplantation on the morphological and functional characteristics of the carotid arteries and heart in a group of end-stage renal failure patients without overt cardiovascular disease, followed up for >3 years. METHODS: Twenty-two patients were evaluated 2-3 weeks after renal transplantation, and again 12 and 40 months post-transplant, using high resolution ultrasound imaging and echocardiography. RESULTS: Kidney and patient survival were 100% at the end of follow-up without any major cardiovascular events. After 40+/-1.2 months, carotid morphological parameters were normalized: carotid intima-media thickness fell from 788+/-24 to 676+/-32 microm (P<0.01) and the carotid wall/lumen ratio fell from 118+/-3 to 103+/-3 microm (P<0.01). Significant reduction of left ventricular (LV) posterior wall thickness (11.5+/-0.2 to 11.3+/-0.2 mm, P<0.05) and LV mass index (172+/-9 to 158+/-8 g/m(2), P<0.01) was already observed after 12+/-0.2 months. Further reduction of LV posterior wall thickness (10.4+/-0.3 mm, P<0.01) and of LV mass index (136+/-7 g/m(2), P<0.01) also occurred after 40+/-1.2 months. However, carotid distensibility (19.5+/-2.1 vs 22+/-2.4, not significant (NS)) and LV compliance (early to atrial flow ratio: 1.2+/-0.1 vs 1.3+/-0.1, NS) remained abnormal, and normalization of the LV mass was attained by only 25% of the patients with LV hypertrophy on baseline. Multiple stepwise regression analysis showed that the rate of change of reduction of the intima-media thickness was influenced by age (negative association, P<0.001) and was positively related to white race (P<0.05), female sex (P<0.01) and to the parallel reduction of maximum carotid diameter (P<0.001). Reduction of LV mass index over time was negatively related to the duration of dialysis treatment and to the parallel increase observed in body mass index and haematocrit, and was positively related to the simultaneous reduction of diastolic blood pressure (P<0.01 for all variables). CONCLUSIONS: Successful renal transplantation improves but does not cause complete regression of the cardiovascular alterations of end-stage renal disease. Only intima-media thickness was normalized by transplantation, whereas LVMI and carotid and ventricular distensibility remained abnormal. The results suggest that extended duration of dialysis, weight gain, high blood pressure and high haematocrit may adversely affect the rate of change of post-transplant cardiovascular hypertrophy.     

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.     

The dilemmas of patient treatment for end-stage renal disease

In past years, physicians responsible for the treatment of chronic uremia have faced dilemmas that have been methodologic and economic while attempting to provide good patient care. These have been overcome, but in the course of time a larger one has developed. The current dilemma is one of high costs for end-stage renal disease (ESRD) management and the failure of current treatment programs to adequately rehabilitate the ESRD patient. In spite of widespread concern about this dilemma, few current data and even fewer projections exist about the eventual costs for their care. Existing data demonstrate several problems that are the basis of this dilemma: (1) the projections of incidence and prevalence of ESRD patients have been too low; (2) renal transplantation has failed to develop into a dominant (and least costly) form of ESRD therapy; (3) home dialysis programs have failed to offset the rapidly expanding in-center dialysis population; and (4) prevalence of and costs for chronic hemodialysis have increased far beyond expected levels. Using current data for the US population as to the incidence and overall mortality rate of ESRD patients, it is apparent that the dialysis population is only 39% of the way toward a steady state-corresponding to only the 4th year of a calculated 25-year growth curve. Although the current costs for maintenance of ESRD patients exceeds $1.3 billion, based upon such projections with the current distribution of patient treatment modalities, the overall annual cost will be in excess of $3.3 billion before a steady state is achieved. Improvement in mortality rates or increases in the incidence of patients will increase the steady state prevalence and the overall costs. Renal transplantation, unless kidney survival rate is increased so that it approximates patient survival, is unlikely to offset the rapidly increasing costs. New technology that would reduce the costs for center-based chronic hemodialysis has not been identified. Emphasis upon home dialysis modalities as a method of increasing patient rehabilitation and reducing costs appears to be a short-term necessity. Increased research and development in prevention of ESRD and in achieving better transplant kidney survival appear to be extremely important as long-term goals.