Cardiovascular Disease In End-stage Renal Disease Patients Research Articles

Correlation of Stromelysin-1 and Tissue Inhibitor of Metalloproteinase-1 with Lipid Profile and Atherogenic Indices in End-Stage Renal Disease Patients: A Neural Network Study

End-stage renal disease (ESRD) patients are prone to cardiovascular disease (CVD). The search for a biomarker that determines patients at great risk of CVD is still a hot topic of study. In the present study, stromelysin-1 and its inhibitor (TIMP1), in addition to atherogenic indices, were studied in ESRD patients. We assessed stromelysin-1, TIMP1, and lipid profile parameters in the serum of 60 ESRD patients and 30 healthy controls. A neural network study was conducted to determine the best factors for predicting ESRD patients more susceptible to developing CVD using the cut-off value of the atherogenic index of plasma (AIP) >0.24. ESRD patients have dyslipidemia, high atherogenic indices, and elevated levels of stromelysin-1 and TIMP1. There is a correlation between the rise in stromelysin-1 and its inhibitor and several atherogenic indices and lipids in those patients. The neural network results indicated that the area under the curve predicting CVD, using the measured eight parameters, was 0.833, with 80 % sensitivity and 100% specificity. The relative importance of the top four most effective input variables that represent the most important determinants for the prediction of high risk of CVD stromelysin-1 (100%), followed by eGFR (77.9%), TIMP1 (66.0%), and TIMP1/stromelysin-1 (30.7%). ESRD patients have dyslipidemia and are prone to CVD, and stromelysin-1 is the best parameter for predicting CVD in ESRD patients.

Gut-derived uremic toxin trimethylamine-N-oxide in cardiovascular disease under end-stage renal disease: an injury mechanism and therapeutic target

The main cause of death in patients with end-stage renal disease (ESRD) is cardiovascular disease, and trimethylamine-N-oxide (TMAO) has been found to be one of the specific risk factors in the pathogenic process in recent years. TMAO is derived from intestinal bacterial metabolism of dietary choline, carnitine and other substances and subsequently catalyzed by flavin monooxygenase enzymes in the liver. The changes of intestinal bacteria in ESRD patients have contributed to the accumulation of gut-derived uremic toxins such as TMAO, indoxyl sulfate and indole-3-acetic acid. While elevated TMAO concentration accelerates atherosclerosis through mechanisms such as inflammation, increased scavenger receptor expression, and inhibition of reverse cholesterol transport. In this review, this research introduces the biological function, metabolic processes of TMAO and mechanisms by which TMAO promotes the progression of cardiovascular disease in ESRD patients and summarizes current interventions that may be used to reverse gut microbiota disturbances, such as activated carbon, fecal microbial transplantation, dietary improvement, probiotic and probiotic introduction. It also focuses on exploring intervention targets to reduce the gut-derived uremic toxin TMAO in order to explore the possibility of more cardiovascular disease treatments for ESRD patients.

High-sensitivity C-reactive Protein as a Marker of Future Cardiovascular Events in Chronic Kidney Disease Stage-5 Patients

Introduction: Chronic Kidney Disease (CKD) has been recognised as a worldwide health threat and understanding its complex patho-physiological mechanisms could go a long way in taking care of patients with CKD. One of the most important causes for mortality in End Stage Renal Disease (ESRD) patients is Cardiovascular Disease (CVD). ESRD is a low grade chronic inflammatory state, suspected to promote atherosclerosis. Aim: To determine, if there is any association between elevated High-sensitivity C-Reactive Protein (hs-CRP) and development of future cardiovascular events in stage-5 CKD patients. Materials and Methods: Forty-five CKD stage-5 patients were included in the study, after ruling out patients with established CVD. According to categorisation proposed by the American Heart Association for the cut-off value of hs-CRP-value (3 mg/L), patients were divided into two groups. Those who had hs-CRP more than 3 mg/L were considered to have ‘elevated hs-CRP’ and those who had a value 3 mg/L and below were considered to have ‘normal hs-CRP’ levels. These patients were followed-up monthly, for a period of one year to record any occurrence of cardiovascular events (coronary events/cerebrovascular accidents/peripheral occlusive vascular disease). Statistical Package for the Social Sciences (SPSS) 16.0 was used for analysis. Chi-square test and Mann-Whitney U-test were used for statistical comparison between the groups and a p-value of 0.05 or less was considered to be statistically significant. Receiver Operating Characteristic (ROC) curve was also plotted to determine the cut-off value for hs-CRP based on the occurrence of any cardiovascular event. Results: Baseline hs-CRP level was more than 3 mg/L in 42% of patients. Among those who had elevated hs-CRP, 78.9% of patients developed cardiovascular events during the follow-up period. This signifies a strong association between elevated hs-CRP and CVD in ESRD patients. The hs-CRP cut-off point of 3 mg/L was obtained from ROC curve. Conclusion: There was a significant association between elevated hs-CRP and development of cardiovascular events in ESRD patients. Hence, hs-CRP can be used as a marker of future cardiovascular events in CKD stage-5 patients.

Evaluation of left ventricular mechanical dyssynchrony with phase analysis in end-stage renal disease patients with normal gated SPECT-MPI.

Phase analysis using gated single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) is a relatively new tool for the assessment of ventricular synchrony. Hypertension, diabetes, renal diseases, and dyslipidemia may affect the phase parameters though their impact is not well understood. The present study aimed to evaluate the incidence of the left ventricular mechanical dyssynchrony (LVMD) in end-stage renal disease (ESRD) patients with normal gated SPECT-MPI and QRS duration (<120 ms) on electrocardiogram. Data of 129 patients (86 males) referred for gated SPECT-MPI for their pretransplant evaluation with normal gated stress SPECT-MPI (SSS <3 and ejection fraction ≥50%) were included in the study analysis. Documented clinical history along with confounding factors such as hypertension, dyslipidemia, smoking, and alcoholism were evaluated. Left ventricle functional (end-diastolic, end-systolic, and LV myocardial volume) and phase parameters (phase standard deviation [PSD], phase bandwidth [PBW] and entropy) were calculated using the QPS-QGS program. LVMD was noted in 36 (28%) of ESRD patients with normal QRS duration and gated SPECT-MPI. The mean attenuated corrected LV myocardial volume, ejection fraction, mean PSD, and PBW values were 84.3 ± 38.1 ml, 65.3 ± 13.5%, 9.8° ± 3.9°, and 61.4° ± 24.7°, respectively. The LV myocardial volume shows statistically significant correlation with the phase parameters (r = 0.31–0.47; P < 0.001). LVMD is present in a significant number of ESRD patients, and its extent is more with increase in LV myocardial volume. It may have an additional role in risk-stratification for cardiovascular disease in ESRD patients.

Abstract 690: Endothelial-Specific Krüppel-Like Factor 2 Inactivation Promotes Endothelial Dysfunction in the Setting of Uremia

Background: Uremic solutes that accumulate in end-stage renal disease (ESRD) contribute to endothelial dysfunction and subsequent cardiovascular disease in ESRD patients. However, the specific mechanisms which mediate uremia-induced endothelial dysfunction in ESRD are not understood. Kruppel-like factors (KLFs) are important regulators of endothelial homeostasis which may be affected by the uremic milieu. In this study, we examined the role and regulation of endothelial KLF2 in mediating endothelial dysfunction in the setting of uremia. Methods and Results: First, we assessed the impact of the uremic milieu on endothelial gene expression utilizing serum from uremic and non-uremic pigs with chronic renal insufficiency. We demonstrate that KLF2 expression was dose-dependently decreased with uremic serum in human umbilical vein endothelial cells (HUVECS) versus normal serum which was reversed by prolonged serum dialysis or the application of laminar shear stress. Carboxymethyl-lysine (CML) modified albumin, a uremic advanced glycation end-product (AGE), also inhibited KLF2 expression. This effect was completely abrogated by receptor for AGE (RAGE) siRNA, as well as by a constitutively active form of IκBα, implicating a role for RAGE activation and the NF-κB signaling pathway. KLF2 suppression also promoted endothelial dysfunction in vitro, as adenoviral overexpression of KLF2 inhibited reactive oxygen species production and leukocyte adhesion in HUVECs treated with uremic serum or CML-AGE. For in vivo translation, we utilized high-frequency ultrasound and quantified flow-mediated dilation of the femoral artery in endothelial-specific KLF2 conditional knockout (cKO) mice after 5 minutes of hindlimb ischemia and demonstrated a 50% reduction in vasodilation in KLF2 cKO mice compared to controls. The lack of femoral artery vasodilation in KLF2 cKO mice was also accompanied by attenuated return of wall shear stress to baseline independent of blood velocity. Conclusions: Collectively, these observations implicate loss of endothelial KLF2 as mediator of endothelial dysfunction in the setting of uremia and suggest that elevating KLF2 expression may be a novel strategy for prevention and treatment of cardiovascular disease in ESRD.

Correlations of MTHFR 677C>T polymorphism with cardiovascular disease in patients with end-stage renal disease: a meta-analysis.

ObjectiveThis meta-analysis was conducted to evaluate the correlations of a common polymorphism (677C>T) in the methylenetetrahydrofolate reductase (MTHFR) gene with risk of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD).MethodThe following electronic databases were searched without language restrictions: Web of Science (1945∼2013), the Cochrane Library Database (Issue 12, 2013), MEDLINE (1966∼2013), EMBASE (1980∼2013), CINAHL (1982∼2013) and the Chinese Biomedical Database (CBM) (1982∼2013). Meta-analysis was performed using STATA statistical software. Odds ratios (ORs) with their 95% confidence intervals (95%CIs) were calculated.ResultsEight cohort studies met all inclusion criteria and were included in this meta-analysis. A total of 2,292 ESRD patients with CVD were involved in this meta-analysis. Our meta-analysis results revealed that the MTHFR 677C>T polymorphism might increase the risk of CVD in ESRD patients (TT vs. CC: OR = 2.75, 95%CI = 1.35∼5.59, P = 0.005; CT+TT vs. CC: OR = 1.39, 95%CI = 1.09∼1.78, P = 0.008; TT vs. CC+CT: OR = 2.52, 95%CI = 1.25∼5.09, P = 0.010; respectively). Further subgroup analysis by ethnicity suggested that the MTHFR 677C>T polymorphism was associated with an elevated risk for CVD in ESRD patients among Asians (TT vs. CC: OR = 3.38, 95%CI = 1.11∼10.28, P = 0.032; CT+TT vs. CC: OR = 1.44, 95%CI = 1.05∼1.97, P = 0.022; TT vs. CC+CT: OR = 3.15, 95%CI = 1.02∼9.72, P = 0.046; respectively), but not among Africans or Caucasians (all P>0.05).ConclusionOur findings indicate that the MTHFR 677C>T polymorphism may be associated with an elevated risk for CVD in ESRD patients, especially among Asians.

Cardiovascular disease in end-stage renal disease

The number of end-stage renal disease (ESRD) patients is progressively growing with more than 60,000 ESRD patients on renal replacement therapy in Korea. The mortality risk in ESRD patients is approximately 10 to 20-fold higher compared to the general population, which is mainly attributed to prevalent cardiovascular disease in these patients. However, the risk factors for cardiovascular disease in ESRD patients are different from the general population, and useful biomarkers for predicting cardiovascular mortality are not completely defined. The nationwide multicenter Clinical Research Center (CRC) for ESRD program was initiated in Korea not only to elucidate the incidence and prevalence of cardiovascular disease in ESRD patients but also to identify potential risk factors including various biomarkers for cardiovascular disease. A prospective cohort of 864 incident hemodialysis patients, from 34 dialysis centers of the CRC for ESRD in Korea, was followed up for 36 months, and the clinical outcome of these patients was reviewed. This article presents the recent data from the CRC for ESRD program, and, in addition, brief reviews on key risk factors and potential biomarkers for cardiovascular disease in ESRD patients.

Paraoxonase-1 and ischemia-modified albumin in patients with end-stage renal disease

End-stage renal disease (ESRD) with and/or without treatment by hemodialysis (HD) is associated with accelerated atherosclerosis, leading to cardiovascular disease (CVD) including acute coronary syndromes. Therefore, the regulation of CVD is a crucial issue for ESRD patients. Given the recent reports that paraoxonase-1 (PON-1) and ischemia-modified albumin (IMA) could predict CVD-related mortality in ESRD, the two recent biomarkers may be useful for preventive strategies for CVD. This review paper presents current data on the relationships between PON-1, IMA, and ESRD. Many studies have shown that circulating PON-1 activity is lower in ESRD patients, and we have shown that its levels increase after HD. Although circulating IMA levels can increase before HD in ESRD patients, there remains to be little data. Our pilot study has shown a significant inverse correlation between PON-1 and IMA in ESRD patients. Although the pathogenic link between PON-1 and IMA remains speculative, considering both biomarkers may provide new insights into the prevention of CVD in ESRD patients.

Complement receptor 1 gene polymorphism and cardiovascular disease in dialyzed end-stage renal disease patients

Inflammation plays an important role in cardiovascular disease (CVD). The complement system is a critical component of innate and acquired immunity. We investigated whether the polymorphisms in the complement receptor 1 (CR1) gene are associated with CVD in end-stage renal disease (ESRD) patients. The study groups of 1200 patients with ESRD, 360 patients with type 2 diabetes and 924 healthy individuals were genotyped. The GG genotype of the C5507G polymorphism was significantly more frequent in ESRD patients with CVD than in patients without CVD and controls (odds ratio [OR] = 3.44, 95% confidence interval [CI] = 2.23–5.3, and OR = 5.46, 95% CI = 3.72–8.0, respectively). The GG genotype was observed in 62% of patients with a history of myocardial infarction. The frequency of the G allele was also higher in patients with CVD (OR = 2.24, 95% CI = 1.93–2.61 vs controls, and OR = 1.97, 95% CI = 1.63–2.36 vs patients without CVD). In the multivariate logistic regression analysis the carrier status of G allele of C5507G polymorphism was an independent risk factor of CVD in ESRD patients ( p < 0.001). In conclusion, our results suggest strong association between the CR1 gene polymorphism and CVD in ESRD patients.

Circulating pro-inflammatory CD4posCD28null T cells are independently associated with cardiovascular disease in ESRD patients

Cytomegalovirus seropositivity is associated with an increased risk for cardiovascular disease in end-stage renal disease (ESRD) patients. Circulating pro-inflammatory CD4posCD28null T cells are expanded in cytomegalovirus-seropositive ESRD patients and potentially could mediate atherosclerotic plaque instability and rupture. In this study, we tested the hypothesis that increased numbers of circulating CD4posCD28null T cells may represent a risk factor for cardiovascular disease in ESRD patients. Prospectively collected data from 240 cytomegalovirus-seropositive stable ESRD patients were analysed. Traditional cardiovascular risk factors (age, smoking, hypercholesterolaemia and diabetes mellitus) and the percentage and absolute number of CD4posCD28null T cells were significantly associated with the presence of atherosclerotic disease, after univariate and multivariate statistical analysis. An ~2-3-fold increase in the prevalence of atherosclerotic disease was noted between patients with the highest and lowest number of CD4posCD28null cells. CD8posCD28null T-cell populations were also significantly expanded in cytomegalovirus-seropositive ESRD patients and closely correlated with the number of CD4posCD28null T cells. However, this cell population was not related to an increased prevalence of cardiovascular disease. Cytomegalovirus-seropositive ESRD patients may have substantially increased numbers of circulating pro-inflammatory CD4posCD28null T cells that are independently associated with the presence of atherosclerotic disease. The expansion of these cells may therefore represent a novel non-traditional cardiovascular risk factor for ESRD patients.

Tumor Necrosis Factor-α Gene Polymorphism Correlates with Cardiovascular Disease in Patients with End-Stage Renal Disease

Tumor necrosis factor-alpha (TNFalpha) is a potent proinflammatory cytokine. Through its effects on lipid metabolism and endothelial function, TNFalpha is involved in cardiovascular disease (CVD). We have studied two polymorphisms in the promoter region of the TNFalpha gene (TNF -308G/A and TNF -238G/A) in end-stage renal disease (ESRD) patients with and without CVD. The aim was to assess the association of these polymorphisms with ESRD and cardiovascular comorbidity in hemodialyzed patients. A total of 603 patients with ESRD treated with hemodialysis (382 patients with CVD) and 325 healthy control subjects were genotyped for the TNF -308G/A and TNF -238G/A ploymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. The A allele of the TNF -308 polymorphism was more frequent in the ESRD group than in control individuals. The odds ratio (OR) for the risk allele was 2.05 (95% CI 1.48, 2.84). In the subgroup of ESRD patients with CVD, the OR was 5.76 (95% CI 3.67, 9.03) relative to ESRD patients without CVD. There was no association observed between the TNF -238 polymorphism and renal failure or CVD in ESRD patients. Our results demonstrate for the first time that the A allele of the TNF -308 polymorphism is associated with CVD in hemodialyzed ESRD patients. If confirmed in prospective studies, it may be a predictor of increased susceptibility to CVD in these patients.

End-stage renal disease causes an imbalance between endothelial and smooth muscle progenitor cells

Patients with end-stage renal disease (ESRD) on hemodialysis have an increased risk of cardiovascular disease (CVD). Circulating endothelial progenitor cells (EPC) contribute to vascular regeneration and repair, thereby protecting against CVD. However, circulating smooth muscle progenitor cells (SPC) may contribute to adverse vascular remodeling. We hypothesized that an imbalance occurs between EPC and SPC in ESRD patients and sampled progenitor cells from 45 ESRD patients receiving regular treatment. Our study is the first to show reduced numbers of CD34+KDR+ hematopoietic stem cell (HSC)-derived EPC (type I EPC). Furthermore, monocyte-derived EPC cultured from mononuclear cells (type II EPC) were reduced in number and had a reduced capacity to stimulate endothelial cell angiogenesis. In contrast, SPC outgrowth was unaffected. In vitro incubation with uremic serum impaired type II EPC outgrowth from healthy donor mononuclear cells and did not influence SPC outgrowth. The hemodialysis procedure itself induced HSC apoptosis and caused an acute depletion of circulating EPC. Taken together, the decreased number and impaired function of EPC are compatible with impaired endogenous vascular repair in hemodialysis patients, whereas the unaffected SPC numbers suggest that the potential of progenitor cells to contribute to adverse remodeling is retained. This EPC-SPC imbalance may contribute to the acceleration of CVD in ESRD patients and could offer novel therapeutic targets.

Adherence of uremic erythrocytes to vascular endothelium decreases endothelial nitric oxide synthase expression

High prevalence of atherosclerotic cardiovascular events accounts for much of the mortality among patients suffering from end-stage renal disease (ESRD). Endothelial dysfunction as a pathogenic mechanism might contribute to increasing the cardiovascular risk of ESRD. Reduced endothelium-dependent vasodilation has consistently been observed in chronic renal failure patients. Since nitric oxide (NO) is the principal endothelium-derived vasodilator, a reduction in the NO bioavailability may be envisaged in ESRD patients. To clarify whether exposure to erythrocytes from ESRD patients might modulate NO release by the endothelium, we evaluated endothelial NO synthase (eNOS) protein levels (Western blot), eNOS mRNA quantity (real-time PCR), and NOS activity (conversion of L-[3H] arginine in L-[3H] citruline) in endothelial cultures stimulated by erythrocytes from healthy subjects and ESRD patients. A time-dependent decrease in eNOS protein levels was evident in cultures treated with erythrocytes from ESRD patients. This observation was consistent with the decreased eNOS mRNA quantities induced by erythrocytes from such patients. Moreover, compared to controls, NOS activity exhibited a significant reduction after incubation with erythrocytes from ESRD patients. The observed eNOS reduction induced by erytrocytes from ESRD patients was totally abolished by annexin V, able to mask red blood cell (RBC) surface-exposed phosphatidylserine. These findings suggest that adhesion of erythrocytes from ESRD patients to vascular endothelium may cause a decrease in the levels of eNOS mRNA and protein, and inhibition of NOS activity. This might contribute to endothelial dysfunction, and may play a role in the pathogenesis of cardiovascular disease in ESRD patients.

Inadequate Treatment of Cardiovascular Disease and Cardiovascular Disease Risk Factors in Dialysis Patients: A Commentary

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Despite its significant impact on health outcomes, which would imply a need for aggressive intervention, both CVD and CVD risk factors are inadequately treated in this patient population. The reasons for this inadequate treatment are unclear. This article reviews the contribution of traditional risk factors to the burden of CVD in ESRD patients, outlines the evidence regarding undertreatment of CVD and traditional CVD risk factors, and identifies potential factors that may be responsible for inadequate cardiovascular care in ESRD patients.

Inflammatory proteins as predictors of cardiovascular disease in patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) are at high risk from potentially devastating cardiovascular sequelae due to the unique clustering of risk factors in these patients. Inflammation is believed to play a key role in the pathogenesis of these cardiovascular lesions. Both pro- and anti-inflammatory cytokines produced from monocytes, and also from adipocytes, have been studied in this regard. Pro-inflammatory cytokines, although cytoprotective acutely, correlate with increased risk of cardiovascular disease (CVD) in chronic situations. Conversely, elevated levels of anti-inflammatory mediators are associated with increased patient survival times. Statistical modelling, calculation of relative risk and cost considerations indicate that determination of serum C-reactive protein levels may be a useful predictor of CVD in ESRD patients. Adipocytes are a rich source of many of the same cytokines produced by monocytes, including interleukin-6, tumour necrosis factor-alpha, as well as adipocyte-specific proteins, leptin and adiponectin (ADPN). ADPN, which is produced in much greater quantities than leptin, is inversely related to body mass index and to insulin resistance, suggesting a possible role in type 2 diabetes. Additionally, ADPN has been shown to modulate the endothelial inflammatory response in vitro. Plasma ADPN levels are an inverse predictor of cardiovascular outcomes among patients with ESRD. Furthermore, ADPN is related to several metabolic risk factors in a manner consistent with the hypothesis that this protein acts as a protective factor for the cardiovascular system.

A functional variant of the myeloperoxidase gene is associated with cardiovascular disease in end-stage renal disease patients

Cardiovascular disease (CVD) is the leading cause of mortality in end-stage renal disease (ESRD) patients and there is emerging evidence that genetic factors may contribute to the development of atherosclerosis. Myeloperoxidase (MPO) is an abundant enzyme involved in the production of free radicals. A functional G-->A single nucleotide polymorphism (SNP) has been identified at position -463, where the A allele is associated with lower MPO expression. To analyze the association between this SNP and inflammation, oxidative stress, and CVD, we studied a cohort of 155 ESRD patients (52 +/- 1 years, 62% males, 22% diabetics) shortly before the initiation of dialysis treatment. CVD was defined by medical history criteria; plasma interleukin-6 (IL-6) was used as a marker of inflammation, and plasma pentosidine as an estimation of oxidative protein damage. DNA from leukocytes was used for genotyping, performed by the pyrosequencing reaction. Only five patients (3%) had the genotype AA at the -463 position, whereas 38 (25%) had the GA and 112 (72%) had the GG genotype. No differences were noted in plasma IL-6 levels between the genotype groups, whereas the pentosidine levels were higher in the GG group (28.4 pmol/mg albumin [range, 8.5 to 123 pmol/mg albumin]) compared to the other two groups (21.4 pmol/mg albumin [range, 7.6 to 384 pmol/mg albumin; P < 0.05]). Patients with the GG genotype had a higher prevalence of positive serology for Chlamydia pneumoniae (51%) when compared to the carriers of the A allele (24%) (P < 0.05). The prevalence of CVD was lower in the AA (0%) and GA genotypes (18%), compared to the GG genotype (35%). The GG genotype was still associated with CVD after correction for age, diabetes, smoking, malnutrition, and inflammation. Our findings suggest that the -463 G-->A SNP, which supposedly results in lower MPO activity, is associated with a lower prevalence of CVD in ESRD patients. It could be speculated that this effect is mediated by a decreased oxidative stress due to lower production of free radicals.

Soluble leptin receptors and serum leptin in end-stage renal disease: relationship with inflammation and body composition.

Elevated serum leptin (S-leptin) levels have been reported in patients with end-stage renal disease (ESRD). Apart from the decreased glomerular filtration rate (GFR), body composition and inflammation may affect leptin levels in ESRD. Leptin circulates both free of and bound to soluble leptin receptors (sOB-R), which are the main determinants of leptin activity and have not been described in ESRD until now. To analyze the association between S-leptin, sOB-R, and inflammation and body composition, we studied 149 (62% males) normal weight (BMI 24.7 +/- 0.4 kg m(-2)) ESRD patients (51 +/- 1 years old) shortly before the start of dialysis (GFR 7.0 +/- 0.2 mL min(-1)). sOB-R and plasma interleukin-6 (IL-6; n= 113) levels were evaluated using ELISA, S-leptin using RIA, and body composition was assessed by X-ray absorptiometry (n = 139). Forty-one healthy subjects age (51 +/- 1 years), BMI (23.6 +/- 0.5 kg m(-2)) and gender-matched (59% males) were used as controls. Median S-leptin was higher in the ESRD patients (10.0 ng mL(-1)) compared with the controls (3.9 ng mL(-1)) (P < 0.001). The median sOB-R did not differ significantly between the ESRD patients (44 U mL-1) and the controls (37 U mL-1). Thus, the sOB-R/S-leptin ratio was lower in the ESRD patients (9.5 +/- 1.2 vs. 12.3 +/- 1.8; P < 0.01) than the controls. A negative correlation was observed between S-leptin and sOB-R (Rho = -0.42; P < 0.0001) in the ESRD patients, a positive correlation was observed between lean body mass and the sOB-R/S-leptin ratio (Rho = 0.33, P = 0.0001) whereas fat mass was negatively correlated to both sOB-R (Rho = -0.26, P = 0.002), and the sOB-R/S-leptin ratio (Rho = -0.62, P < 0.0001). Positive correlations were observed between IL-6 and S-leptin (Rho = 0.19; P < 0.05) and weak but significant body fat mass (Rho = 0.20; P < 0.05), respectively. This study demonstrates that despite markedly elevated S-leptin levels in the ESRD patients, sOB-R did not differ from the controls. In view of the anorexigenic and pro-atherogenic effects of leptin, further elucidation of the consequences of free bioactive leptin in the development of complications such as malnutrition and cardiovascular disease in ESRD patients is required.

Cardiovascular disease in end-stage renal disease patients

This study evaluates risk factor monitoring in end-stage renal disease (ESRD) patients with cardiovascular disease. Death rates from cardiovascular disease in ESRD patients are 20 to 40 times higher than in the general population, and 72% of ESRD patients with an acute myocardial infarction (AMI) are dead within 2 years of follow-up. Patients who have sustained an AMI rarely receive definitive testing to assess coronary circulation, and cardiac catheterization rates and revascularization rates are low, even after the high-risk event of an AMI. Risk factor intervention to treat lipid disorders in the ESRD population has received little attention, with the USRDS reporting that in 1998, 58% of dialysis and 64% of transplant patients had no lipid monitoring performed within a year. Of those tested, only 33% of dialysis and 27% of transplant patients had two or more tests within 1 year. Glycemic control monitoring in the form of HbA1c, recommended for diabetes management, is also underutilized in ESRD patients, with fewer than half receiving a single test within 1 year and only 10% receiving three or more tests. This raises concerns that diabetic glycemic control monitoring may be suboptimal in the ESRD population. The use of diabetic eye examinations and diabetic glucose monitoring is also low, as are influenza vaccination rates. These data suggest that the clinical care of cardiovascular disease in the ESRD patients needs more attention. © 2001 by the National Kidney Foundation, Inc.

Cardiac Disease in Chronic Uremia: Investigation

Cardiovascular disease continues to be the leading cause of death in the end-stage renal disease (ESRD) population, accounting for nearly half of the deaths among the dialysis population. The purpose of this article is to review the clinical screening tools available to the attending nephrologist and consulting cardiologist to detect both symptomatic and asymptomatic cardiovascular disease in ESRD patients. The author presents a detailed overview of (1) assessment of left ventricular (LV) function in the hemodialysis population and (2) noninvasive cardiovascular screening in patients before anticipated renal transplantation. Specific guidelines are offered for the pretransplantation evaluation of cardiac disease based on the patient's cardiovascular risk factors, symptomatology, and stress testing with either thallium or dobutamine echocardiography. Recent studies of cardiovascular screening in selected hemodialysis populations may not be extrapolated to the general ESRD population pending further investigation. Crucial questions relating to the utility of cardiovascular screening and intervention in the general ESRD population remain and deserve further study.