High Hemoglobin A1c levels and glycemic variability increase risk of severe hypoglycemia in diabetic hemodialysis patients

While hyperglycemia is central to the pathogenesis and management of diabetes mellitus, hypoglycemia and glucose variability also contribute to outcomes. We previously reported on the relationship of glycemic control to outcomes in a large population of diabetic end‐stage renal disease (ESRD) patients. Recognizing that ESRD is a risk factor for severe hypoglycemia, we have now analyzed the association between glycosylated hemoglobin A1c (HgbA1c) levels and glycemic variability in those with hypoglycemia. This is a retrospective study of patients with diabetes enrolled in a large hemodialysis program. Hypoglycemia was identified from hospital discharge diagnostic codes. Glycemic variability was assessed by the standard deviation of HgbA1c and glucose levels over time. Hypoglycemia as a discharge diagnosis was documented in 4.1% of patients. Higher baseline HgbA1c was associated with greater risk for hypoglycemia hospitalization, a finding confirmed by time‐lagged HgbA1c levels drawn a quarter earlier. Higher baseline HgbA1c categories were also associated with greater variability in HgbA1c levels during the analysis period. Similarly, greater glucose variability was associated with higher mean glucose levels by trend analysis. High, not low, HgbA1c levels are associated with greater risk of severe hypoglycemia, which may derive from glucose variability in the setting of treatment for hyperglycemia. High HgbA1c and glycemic variability are associated with increased risk of hypoglycemia in individuals with diabetes and ESRD.     

The greatly misunderstood erythropoietin resistance index and the case for a new responsiveness measure

Introduction The optimal use of erythropoiesis stimulating agents (ESAs) to treat anemia in end stage renal disease remains controversial due to reported associations with adverse events. In analyzing these associations, studies often utilize ESA resistance indices (ERIs), to characterize a patient's response to ESA. In this study, we examine whether ERI is an adequate measure of ESA resistance. Methods We used retrospective data from a nonconcurrent cohort study of incident hemodialysis patients in the United States (n = 9386). ERI is defined as average weekly erythropoietin (EPO) dose per kg body weight (wt) per average hemoglobin (Hgb), over a 3‐month period (ERI = (EPO/wt)/Hgb). Linear regression was used to demonstrate the relationship between ERI and weight‐adjusted EPO. The coefficient of variation was used to compare the variability of Hgb with that of weight‐adjusted EPO to explain this relationship. This analysis was done for each quarter during the first year of dialysis. Findings ERI is strongly linearly related with weight‐adjusted EPO dose in each of the four quarters by the equation ERI = 0.0899*(EPO/wt) (range of R² = 0.97–0.98) and weakly linearly related to 1/Hgb (range of R² = 0.06–0.16). These correlations hold independent of age, sex, hgb level, ERI level, and epo‐naïve stratifications. Discussion ERI is strongly linearly related to weight‐adjusted (and nonweight‐adjusted) EPO dose by a “universal,” not patient‐specific formula, and thus is a surrogate of EPO dose. Therefore, associations between ERI and clinical outcomes are associations between a confounded EPO dose and those outcomes.     

Anti‐inflammatory effects of linagliptin in hemodialysis patients with diabetes

Inflammation and glycemic control are important prognosis‐related factors for hemodialysis (HD) patients; moreover, inflammation affects insulin secretion. Here, we evaluated the anti‐inflammatory effects of monotherapy with linagliptin—a dipeptidase‐4 inhibitor—in HD patients with type 2 diabetes. We examined 21 diabetic HD patients who were not receiving oral diabetes drugs or insulin therapy and with poor glycemic control (glycated albumin [GA] level, >20%). Linagliptin (5 mg) was administered to the patients daily. The levels of prostaglandin E2 (PGE2), interleukin‐6 (IL‐6), high‐sensitivity C‐reactive protein, GA, blood glucose, and active glucagon‐like peptide‐1 were determined before and 6 months after treatment. Body weight and serum levels of albumin, hemoglobin, total cholesterol, and low‐density lipoprotein cholesterol were also recorded before and after treatment. The levels of PGE2 and GA were significantly decreased 1 month after starting linagliptin therapy, whereas the IL‐6 levels were significantly decreased 6 months after starting linagliptin therapy. After 6 months of treatment, the PGE2 levels decreased from 188 ± 50 ng/mL to 26 ± 5 ng/mL; IL‐6 levels, from 1.5 ± 0.4 pg/mL to 0.6 ± 0.1 pg/mL; and GA levels, from 21.3% ± 0.6% to 18.0% ± 0.6%. Glucagon‐like peptide‐1 levels increased 2.5‐fold during the treatment. Over the 6‐month treatment period, body weight and levels of high‐sensitivity C‐reactive protein, blood glucose, albumin, hemoglobin, and cholesterol did not change; none of the patients exhibited hypoglycemia. The anti‐inflammatory effects of linagliptin monotherapy indicate that it may serve as a useful glucose control strategy for HD patients with diabetes.     

Perihospitalization patterns of hemoglobin levels and erythropoiesis‐stimulating agent doses in US hemodialysis patients, 1998–2009

Anemia management in hemodialysis patients is of primary importance for clinicians and dialysis providers. Through a retrospective claims analysis, we studied prevalent US hemodialysis patients 1998–2009, and examined patterns of hemoglobin levels and erythropoiesis‐stimulating agent (ESA, epoetin [EPO], and darbepoetin [DPO] ) doses surrounding hospitalization events. Medicare outpatient claims were used to determine monthly ESA doses and associated hemoglobin levels. ESA dose trajectories were defined with repeated measures models incorporating an autoregressive covariance matrix that compared subsequent measurements with the index month of hospitalization, with variance component covariance matrices chosen for pair‐wise comparisons. Regarding prehospitalization hemoglobin levels, a biphasic pattern occurred in both the EPO (1998–2009, n = 161,242) and DPO (2004–2009, n = 4391) populations; levels rose from 1998 to 2004, fell thereafter in the EPO population, and fell after 2006 or 2007 in the DPO population. In the EPO population, the proportions of patients with hemoglobin less than 10 g/dL were 30.1% in 1998, 14.5% in 2004, and 28.3% in 2009; corresponding values for the DPO population were 21.0% in 2004 and 31.6% in 2009. While some degree of year‐to‐year variability occurred, EPO dose trends were less pronounced, with an apparent peak in 2004 followed by a modest decline; trends were similar for DPO. Trends in EPO dose trajectories did not completely parallel those for hemoglobin level; while EPO doses increased yearly up to 2004, doses stabilized, but did not materially decrease after 2004. No definite annual trends for DPO dose trajectories were apparent.     

Is there any interaction of resistin and adiponectin levels with protein‐energy wasting among patients with chronic kidney disease

The aim of this study was to evaluate the effects of adipocytokines including adiponectin, leptin, resistin, neuropeptide Y and ghrelin in chronic kidney disease (CKD) patients on appearance of protein‐energy wasting (PEW). One hundred fifty patients with mean age of 45.4 ± 15.9 years, without active infections or chronic inflammatory conditions were recruited into the study. Study groups were control group (consisting of 30 healthy volunteers with normal kidney functions), hemodialysis group, predialysis group, peritoneal dialysis group and kidney transplant group. Fasting morning serum leptin, ghrelin, acylated ghrelin, neuropeptide Y, adiponectin, resistin levels of all of the groups were measured. Anthropometric and nutritional assessments of all patients were obtained. Diagnosis of PEW was made according to definition recommended by the International Society of Renal Nutrition and Metabolism. Presence of PEW in hemodialysis (23.3%) and peritoneal dialysis (26.7%) groups were significantly higher than those of predialysis (3.3%), and transplantation (0%) groups. Adiponectin and resistin levels in predialysis, peritoneal dialysis and hemodialysis patients were significantly higher than control group (p: 0.0001). This study had given significant positive correlations between presence of PEW and serum resistin (r: 0.267, p: 0.001), and serum adiponectin levels (r: 0.349, p: 0.0001). There were no relationship between presence of PEW and ghrelin, acylated‐ghrelin, neuropeptide Y, and leptin levels of the groups. CKD patients except transplant patients had higher adiponectin and resistin levels than control group. PEW was found to be linearly correlated with resistin and adiponectin. High serum resistin and adiponectin levels might have a role in development of PEW among dialysis patients.     

Costs of managing anemia with erythropoiesis‐stimulating agents during hemodialysis: A time and motion study

Use of erythropoiesis‐stimulating agents (ESAs) presents a significant time and cost burden in the management of anemia of chronic kidney disease (CKD). We conducted a prospective, observational, activity‐based costing study to estimate the health care personnel time and resulting direct medical costs associated with administering epoetin 3 times weekly to patients with end‐stage renal disease on dialysis. The study was conducted at 5 US hemodialysis centers. The personnel time and costs were derived from time and motion observations. Predicted time and cost savings were modeled for switching patients to once‐monthly ESA therapy. Patients also completed a survey questionnaire to assess their level of CKD knowledge and information needs. Total per‐patient‐per‐year (PPPY) time expended on anemia management with epoetin averaged 608 minutes (range 512–915 minutes), with an average PPPY cost of $548 (range $342–$651). Use of a once‐monthly ESA, compared with epoetin, could decrease average PPPY time expenditure by 79% (127 minutes [range 96–173 minutes]) and reduce PPPY costs by 81% ($104 [range $79–$136]). The patient questionnaire reported insufficient education on CKD. Use of a once‐monthly ESA to correct anemia in dialysis patients may provide substantial time, resource, and cost savings compared with current treatment practices.     

Iron storage indices and risk of bacterial infections in hemodialysis patients

Background: Infection is the second leading cause of death among hemodialysis (HD) patients. Because iron overload may be a risk factor for bacterial infection, concerns about excessive use of intravenous (IV) iron have arisen. In this retrospective analysis, we explored the relationship between target iron storage indices, as outlined in the Dialysis Outcomes Quality Initiative (DOQI) guidelines, and the incidence of bacterial infections. Methods: We reviewed the charts of 87 HD patients who received their first course of IV iron at our dialysis unit between 1997 and 2001. Transferrin saturation (TSAT) rate, ferritin level, and other clinical/laboratory measures were recorded at baseline. Patients were followed for up to 2 years for the outcomes of bacteremia and bacterial pneumonia and censored at death, end‐of‐study observation, or kidney transplantation. Cox proportional hazards regression was used to evaluate the relationship of bacterial infections to iron storage indices. Results: Thirty‐two patients had at least one episode of bacterial infections. In multivariate analyses, after adjusting for sex and venous catheter use, iron‐replete state (ferritin > 100 ng/mL and TSAT > 20%) was associated with a threefold higher risk of bacterial infections (95% CI 1.3–6.6; p = 0.01). Although diabetes mellitus and lower serum albumin had a nonsignificant trend toward an increased risk of bacterial infections, no such relationship was seen with the first 3‐month cumulative IV iron dose. Conclusions: This study suggests an increased risk for bacterial infections at modest levels of iron stores (ferritin > 100 ng/mL and TSAT > 20%) among HD patients initiating IV iron. Large prospective studies are needed to confirm these relationships.     

Factors Affecting Flow-Mediated Vasodilatation in Hemodialysis Patients

Clinical manifestation of overt vascular disease may be preceded for years by endothelial dysfunction. Objective: This study was undertaken to evaluate endothelial function in ESRD patients and correlation between endothelial function and clinical and biochemical parameters. Methods: 32 stable ESRD patients (male : female = 16 : 16, average age: 55.2 ± 13.0) on hemodialysis were included. A 10‐MHz ultrasound transducer was used to image the brachial artery. Brachial artery diameter was measured, and reactive hyperemia was induced by inflation to 250 mmHg for 5 min and then deflation of a pneumatic cuff. After release of the cuff, brachial artery diameter was measured. Results: In the entire study population and non‐diabetic group, the %FMD (% flow‐mediated dilatation, % change of brachial artery diameter between before and after cuff inflation) did not show any significant correlation with duration of dialysis, age, hypertension, albumin, CRP, total cholesterol, LDL and HDL cholesterol, and triglyceride. However, the %FMD of diabetic patients was lower than that of non‐diabetics. Among the patients with diabetes, the group of patients with FMD of <5.2% showed significant lower serum albumin and significantly higher ln(CRP) levels compared to the group of patients with FMD ≥5.2%. The %FMD showed significant positive correlation with serum albumin level and significant negative correlation with ln(CRP) in diabetic patients. Conclusion: These findings suggest that endothelial dysfunction, estimated by FMD, was significantly more prominent in diabetic ESRD, especially with low serum albumin and high CRP levels.     

Tailoring dialysis and resuming low‐protein diets may favor chronic dialysis discontinuation: Report on three cases

Renal function recovery (RFR), defined as the discontinuation of dialysis after 3 months of replacement therapy, is reported in about 1% of chronic dialysis patients. The role of personalized, intensive dialysis schedules and of resuming low‐protein diets has not been studied to date. This report describes three patients with RFR who were recently treated at a new dialysis unit set up to offer intensive hemodialysis. All three patients were females, aged 73, 75, and 78 years. Kidney disease included vascular‐cholesterol emboli, diabetic nephropathy and vascular and dysmetabolic disease. At time of RFR, the patients had been dialysis‐dependent from 3 months to 1 year. Dialysis was started with different schedules and was progressively discontinued with a “decremental” policy, progressively decreasing number and duration of the sessions. A moderately restricted low‐protein diet (proteins 0.6 g/kg/day) was started immediately after dialysis discontinuation. The most recent update showed that two patients are well off dialysis for 5 and 6 months; the diabetic patient died (sudden death) 3 months after dialysis discontinuation. Within the limits of small numbers, our case series may suggest a role for personalized dialysis treatments and for including low‐protein diets in the therapy, in enhancing long‐term RFR in elderly dialysis patients.     

Changes in biochemical,hemodynamic, and dialysis adherence parameters in hemodialysis patients during Ramadan

This paper aimed to study the effect of Ramadan fasting on biochemical and clinical parameters and compliance for dialysis. A prospective multicenter observational cross‐sectional study comparing fasting with a non‐fasting stable adult hemodialysis patients for demographic and biochemical parameters, compliance with dialysis, inter‐dialytic weight gain, pre‐ and post‐blood pressure, and frequency of intradialytic hypotensive episodes was carried out. Six hundred thirty‐five patients, of whom 64.1% fasted, were studied. The fasters were younger (53.3 ± 16.2 vs. 58.4 ± 16.1 years; P = 0.001) but had similar duration on dialysis (P = 0.35). More fasters worked (22.0% vs. 14.6%; P = 0.001) and missed dialysis sessions during Ramadan. No differences were noted between groups in sex, diabetic status, or dialysis shift or day. There were no differences in the pre‐ and post‐dialysis blood pressure; serum potassium, albumin or weight gain; diabetic status; sex; and dialysis shift time or days. However, serum phosphorous was significantly higher in the fasting group (2.78 ± 1.8 vs. 2.45 ± 1.6 mmol/L; P = 0.045). There were no intragroup differences in any of the parameters studied when comparing the findings during Ramadan with those in the month before Ramadan. Fasters were significantly younger and more likely to be working, to miss dialysis sessions, and to have higher serum phosphorous levels. No other differences were observed.     

Raman spectroscopy-based sensitive and specific detection of glycated hemoglobin

In recent years, glycated hemoglobin (HbA1c) has been increasingly accepted as a functional metric of mean blood glucose in the treatment of diabetic patients. Importantly, HbA1c provides an alternate measure of total glycemic exposure due to the representation of blood glucose throughout the day, including post-prandially. In this article, we propose and demonstrate the potential of Raman spectroscopy as a novel analytical method for quantitative detection of HbA1c, without using external dyes or reagents. Using the drop coating deposition Raman (DCDR) technique, we observe that the nonenzymatic glycosylation (glycation) of the hemoglobin molecule results in subtle but discernible and highly reproducible changes in the acquired spectra, which enable the accurate determination of glycated and nonglycated hemoglobin using standard chemometric methods. The acquired Raman spectra display excellent reproducibility of spectral characteristics at different locations in the drop and show a linear dependence of the spectral intensity on the analyte concentration. Furthermore, in hemolysate models, the developed multivariate calibration models for HbA1c show a high degree of prediction accuracy and precision--with a limit of detection that is a factor of ~15 smaller than the lowest physiological concentrations encountered in clinical practice. The excellent accuracy and reproducibility achieved in this proof-of-concept study opens substantive avenues for characterization and quantification of the glycosylation status of (therapeutic) proteins, which are widely used for biopharmaceutical development. We also envision that the proposed approach can provide a powerful tool for high-throughput HbA1c sensing in multicomponent mixtures and potentially in hemolysate and whole blood lysate samples.     

Role of bicarbonate dialysis in prevention of serious arrhythmias in high‐risk cardiac patients undergoing regular hemodialysis

Background: Cardiac arrhythmias are considered as one of the most important causes of mortality in patients on hemodialysis. Arrhythmias frequently occur in patients with chronic renal failure on regular hemodialysis with reported incidences varying from 30–48% of patients. These abnormalities can span from supraventricular to severe ventricular arrhythmia. There is an increased frequency of occurrence and clustering of arrhythmias around the dialysis time. Aim of the study: To detect the difference between acetate and bicarbonate dialysis as regard to the type and frequency of arrhythmia in those patients. Study design: This study was done on 20 male patients age 51–73, all have history of heart disease. Patients were divided into 2 equal groups using acetate in group 1 and bicarbonate in group 2. All patients were on regular hemodialysis (4 hours, thrice weekly). Careful history and clinical examination were done. Pre‐dialysis investigations included serum creatinine, blood urea nitrogen, serum sodium, potassium, calcium and phosphorus, serum albumin, hemoglobin, and arterial blood gases. Post‐dialysis serum potassium and arterial blood gases were measured. ECG and forty‐eight hours ambulatory monitor (Holter monitor)(before, during, and after hemodialysis, till the end of the dialysis day and throughout the following day) were performed. Results: Group 1 showed significantly less post‐dialysis supraventricular arrhythmias than in dialysis day (210.9 ± 236 and 62.3 ± 14.4), respectively. Significantly less ventricular arrhythmias in post‐dialysis than in dialysis day (30.7 ± 50.4, and 106.2 ± 128.4), respectively. While in Group 2 there were insignificant differences regarding supraventricular arrhythmias (21.9 ± 28.9 and 16.6 ± 36.3) and ventricular arrhythmias (22.9 + 7.8 and 29.6 + 12.8) in dialysis day than in post‐dialysis day. There was significantly higher frequency of supraventricular and ventricular arrhythmias in the dialysis day in acetate hemodialysis in comparison to bicarbonate hemodialysis. Conclusion: Bicarbonate hemodialysis is less arrhythmogenic in comparison to acetate hemodialysis and has better effect on the blood pH and greater degree of base repletion. Continuous ambulatory ECG recording (Holter) is a useful tool in detecting arrhythmias in dialysis patients.     

Human hemolysate glycated proteome

Despite continuous advances in hyperglycemia treatments, a precise control through monitoring of glucose and glycated hemoglobin remains in most diabetic patients as the diagnosis/prognosis tool. An alternative perspective could be the discovery and quantitation of new blood glycated proteins formed by nonenzymatic reaction with circulatory glucose. As a result, the human hemolysate is an incomparable source of glycated proteins to further monitor glycemia and interpret changes at the level of this post-translational modification. The human hemolysate is here studied based on the differential labeling of proteins with isotopically labeled-glucose ([(13)C(6)] glucose), named glycation isotopic labeling. Due to the chemoselectivity of glycation, only preferential targets are labeled by this protocol. The approach provides qualitative data through the detection of preferential protein glycation sites as well as quantitative information to evaluate the abundance of this modification. This strategy was applied to human hemolysate samples corresponding to different glycemic states estimated by laboratory-certified concentrations of glycated hemoglobin. The glycation level of each protein can then be employed to interpret the effect of glucose exposition as a consequence of glycemic unbalance. This information should provide new molecular insights into protein glycation mechanisms that might generate a new hypothesis to clinicians to improve the understanding of underlying pathologies associated to prolonged hyperglycemia.     

A systematic review of the benefits and harms of dipeptidyl peptidase‐4 inhibitor for chronic kidney disease

Introduction: Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) and the optimal glycemic control is key to delay the progression of the disease and prevent major complications. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors have emerged as a promising therapeutic option. However, the benefits and harms of the treatment have yet to be clarified for diabetic patients with CKD. Methods: Type 2 diabetic patients with moderate to severe CKD including end‐stage renal disease were eligible and randomized controlled trials comparing DPP‐4 inhibitors with no treatment or placebo or other antihyperglycemic agents were included. A systematic electronic search was conducted through the Medline Ovid, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. Findings: Six placebo/open and 2 active controlled trials (1747 participants) were included. The adjusted mean difference of hemoglobin A_1c between DPP‐4 inhibitors and placebo ranged from ?0.60% to ?0.42%. The odds ratio of hypoglycemia, mortality and severe adverse effects due to all types of DPP‐4 inhibitors were 1.35 (95% CI: 0.98–1.84), 0.88 (95% CI: 0.42–1.86) and 0.86 (95% CI: 0.65–1.15), respectively while that due to DPP‐4 inhibitors with renal clearance were 1.40 (95% CI: 0.87 to 2.24), 0.85 (95% CI: 0.35 to 2.04) and 0.91 (95% CI: 0.63 to 1.32), respectively. Discussion: DPP‐4 inhibitors demonstrated beneficial effects on the glycemic control for diabetic patients with CKD without causing any additional adverse effects. However, a definitive conclusion has yet to be drawn due to serious methodological problems and a small number of studies.     

Causes and consequences of inflammation on anemia management in hemodialysis patients

Inflammation is common among hemodialysis patients, and evidence is accumulating to suggest that inflammation is a major contributor to morbidity and mortality. Several factors have been suggested as potential causes of inflammation, including infections and the atherosclerosis process, as well as etiologies directly related to kidney disease such as reduced renal function and dialysis. Among several inflammatory biomarkers investigated, serum C-reactive protein (CRP) is the most widely used. In hemodialysis patients, raised CRP levels have been shown to be predictive of cardiovascular events, hospitalization, and all-cause and cardiovascular mortality. Elevated CRP levels may correlate with comorbidities and intercurrent events, all of which may impact the response to erythropoiesis-stimulating agents (ESAs) and lead to higher ESA doses. Most dialysis facilities do not routinely measure CRP, despite recommendations by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative. Regular measurement of CRP levels may help providers to understand change in ESA dosing and identify patients at risk for cardiovascular events. This review explores the inter-relationships between inflammation, CRP levels, and anemia management in patients receiving hemodialysis.     

Erythropoietin‐stimulating agents in the management of anemia of end‐stage renal disease patients on regular hemodialysis: A prospective randomized comparative study from Qatar

Despite extensive use, to the best of our knowledge, no trial has simultaneously compared the three currently used erythropoietin‐stimulating agents (ESAs) in a prospective manner in the treatment of anemia of end‐stage renal disease patients. All hemodialysis patients in Qatar who were treated with short‐acting epoetin alfa or beta have been screened. Eligible patients had been prospectively randomized, either to continue on the previous regimen of epoetin or to receive darbepoetin alfa or continuous erythropoietin receptor activator (CERA) for a total period of 40 weeks. All groups were assessed at the end of the study for safety and efficacy parameters. A total of 327 eligible patients were randomized. Mean hemoglobin concentration remained constant within the recommended target range (11–12 g/dL) throughout the study in the three studied groups. The percentage of patients who reached the target range was constantly above 50% in the second half of the study among CERA group patients who also had significantly lower mean number of dose adjustments as compared with the other two groups (P = 0.001). Similarly, the number of discontinuations of ESA among epoetin, darbepoetin, and CERA groups was 17, 19, and 9, respectively (P = 0.042). The frequencies of adverse events were similar in all groups. This study has specifically compared the effect of ESA type on the variability of serum hemoglobin levels in hemodialysis patients. Furthermore, it confirmed the efficacy and safety of once monthly CERA for maintaining tight hemoglobin control within recommended target ranges.     

Coronary and aortic calcifications in patients new to dialysis

Background: Vascular calcification has been associated with all cause and cardiovascular mortality in patients with end‐stage kidney disease (ESRD). Whether vascular calcification is present in persons with advanced chronic kidney disease starting dialysis or develops in patients on dialysis is unknown. The purpose of this study was to examine the prevalence of vascular and coronary calcification in patients new to hemodialysis. Methods: A total of 129 subjects new to dialysis were evaluated using electron beam computed tomography. The primary outcome was the presence and extent of coronary artery, aortic, and valvular calcification. Results: Forty‐three percent of subjects had no significant coronary artery calcification (total score ≤ 30) and 27% had no detectable aortic calcification. Thirty‐four percent had coronary artery scores that placed them above the 90th percentile for age and sex. Coronary artery calcification was significantly associated with a history of coronary artery disease and atherosclerotic vascular disease (ASVD) whereas aortic calcification was significantly associated with ASVD. Age (p < 0.0001), pulse pressure (p = 0.004), diabetes mellitus (p = 0.009), and a history of smoking (p = 0.026) were independently associated with the extent of coronary artery calcification. Age (p < 0.0001) and pulse pressure (p = 0.0003) were independently associated with the extent of aortic calcification. Conclusions: A large fraction of patients new to hemodialysis had no evidence of coronary artery or aortic calcification. Coupled with the extensive vascular calcification reported by others in prevalent dialysis patients these findings suggest that dialysis‐specific factors contribute to calcific vascular disease in ESRD.     

Confounding factors for early death in incident end‐stage renal disease patients: Role of emergency dialysis start

Hemodialysis (HD) has been associated with higher 1‐year mortality than peritoneal dialysis (PD) after dialysis start. Confounding effects of late referral, emergency dialysis start, or start with central venous catheter on this association have never been studied concomitantly. Survival was studied among the 495 incident dialysed patients in our department from 1995 to 2006 and followed at least 1 year until December 31, 2007. Nested Cox models adjusted on patient characteristics explored factors associated with 1‐year and ≥1‐year mortality. Hemodialysis patients were 332 (67.1%), 104 (21.0%) were late referred (<6 months), 167 (33.7%) started dialysis in emergency, and 144 (29.1%) started with central venous catheter. When adjusted only on age, sex, and comorbidities, HD was associated with poor 1‐year outcome: adjusted hazard ratio (aHR) for death in HD vs. PD was 1.77, P=0.02. In fully adjusted model, among first dialysis feature variables, only emergency dialysis start was significantly associated with 1‐year mortality: aHR 1.53, P=0.02. Dialysis modality was not associated with 1‐year mortality rates in this fully adjusted model: aHR in HD vs. PD became 1.03, P=0.91. In ≥1‐year period, HD was associated with lower mortality than PD (aHR 0.61, P=0.004), whereas other first dialysis features were not associated with death. Other factors associated with death were age, type 2 diabetes, peripheral vascular disease, heart failure, and hepatic failure. Negative association between HD and 1‐year survival on dialysis was explained by confounders. Emergency dialysis start was strongly associated with early mortality on dialysis. Its prevention may improve patient survival.     

Differences in cardiovascular mortality rates among hemodialysis patients in the United States and Japan: The importance of background cardiovascular mortality

Mortality rates among hemodialysis patients differ greatly among the United States, Europe, and Japan and it has been hypothesized that this is mainly due to differences in practice patterns. Results from the international DOPPS study, however, indicate that differences in practice patterns among the United States, Japan, and Europe are small and not alone explanatory for the differences in mortality rates. Ethnic variability in predisposition to atherosclerotic cardiovascular disease in the general population may lead to significant differences in background cardiovascular mortality in the United States, Japan, and Europe. It is our hypothesis that cardiovascular mortality in dialysis patients is to a great extent dependent on cardiovascular background mortality of the general population. We are currently studying the relationship between all‐cause and cardiovascular death rates in countries worldwide using the WHO database. Preliminary data from 35 countries show that all‐cause and cardiovascular death rates differ significantly among regions, with Eastern European countries reporting four‐ to sevenfold higher death rates than Asian countries. A strong linear relationship between cardiovascular and all‐cause death rates is observed among these countries. The next step of our study will be to compare country‐specific cardiovascular death rates of dialysis populations with those of the respective general populations. Ethnic differences in cardiovascular morbidity and mortality may be explained by genetic variability based upon polymorphism of genes involved in the pathogenesis of atherosclerosis and myocardial infarction.     

Prevalence of the metabolic syndrome in an incident dialysis population

The National Heart, Lung, and Blood Institute's National Cholesterol Education Program 2001 Adult Treatment Panel III report defined the metabolic syndrome as having at least 3 of the following 5 criteria: abdominal obesity, elevated triglyceride levels, low high-density lipoprotein cholesterol levels, an elevated blood pressure, and an elevated fasting glucose. Evidence is accumulating to suggest that the metabolic syndrome predisposes to cardiovascular disease (CVD). End-stage kidney disease (ESKD) patients requiring dialysis have a substantially elevated risk of CVD morbidity and mortality. Dialysis patients' increased risk can be partially explained by traditional and nontraditional risk factors. The prevalence of the metabolic syndrome in dialysis patients is unknown. This retrospective, cross-sectional study of 202 incident dialysis patients examined the prevalence of the metabolic syndrome at the time of renal replacement therapy initiation. The study group was compared with all incident dialysis patients in 2002 on file with the U.S. Renal Data System. Females represented 39.1% of the study population. Blacks composed 34.7% of the study group. Diabetes was the etiology of ESKD in 44.6% of our patients. Surrogate criteria were used for the Adult Treatment Panel III risk factors of abdominal obesity and elevated fasting glucose levels. Overall, the prevalence of the metabolic syndrome was 69.3% in our population and was especially prevalent among diabetic, female, and white ESKD patients. Study limitations included the use of surrogate markers for 2 criteria of the metabolic syndrome and dependence on the Medical Evidence Report (Form 2728) for baseline characteristics. In summary, the metabolic syndrome is highly prevalent in incident dialysis patients.