The Glycemic Indices in Dialysis Evaluation (GIDE) study: Comparative measures of glycemic control in diabetic dialysis patients

The validity of hemoglobin A1c (HgbA1c) is undergoing increasing scrutiny in the advanced CKD/ESRD (chronic kidney disease/end‐stage renal disease) population, where it appears to be discordant from other glycemic indices. In the Glycemic Indices in Dialysis Evaluation (GIDE) Study, we sought to assess correlation of HgbA1c with casual glucose, glycated albumin, and serum fructosamine in a large group of diabetic patients on dialysis. From 26 dialysis facilities in the United States, 1758 diabetic patients (hemodialysis = 1476, peritoneal dialysis = 282) were enrolled in the first quarter of 2013. The distributions of HgbA1c and the other glycemic indices were analyzed. Intra‐patient coefficients of variation and correlations among the four glycemic indices were determined. Patients with low HgbA1c values were both on higher erythropoietin (ESA) doses and more anemic. Serum glucose exhibited the highest intra‐patient variability over a 3‐month period; variability was modest among the other glycemic indices, and least with HgbA1c. Statistical analyses inclusive of all glycemic markers indicated modest to strong correlations. HgbA1c was more likely to be in the target range than glycated albumin or serum fructosamine, suggesting factors which may or may not be directly related to glycemic control, including anemia, ESA management, and iron administration, in interpreting HgbA1c values. These initial results from the GIDE Study clarify laboratory correlations among glycemic indices and add to concerns about reliance on HgbA1c in patients with diabetes and advanced kidney disease.     

Glucose‐Responsive Composite Microneedle Patch for Hypoglycemia‐Triggered Delivery of Native Glucagon

Insulin‐dependent patients with diabetes mellitus require multiple daily injections of exogenous insulin to combat hyperglycemia. However, administration of excess insulin can lead to hypoglycemia, a life‐threatening condition characterized by abnormally low blood glucose levels (BGLs). To prevent hypoglycemia associated with intensive insulin therapy, a “smart” composite microneedle (cMN) patch is developed, which releases native glucagon at low glucose levels. The cMN patch is composed of a photo‐crosslinked methacrylated hyaluronic acid (MeHA) microneedle array with embedded multifunctional microgels. The microgels incorporate zwitterionic moieties that stabilize loaded glucagon and phenylboronic acid moieties that provide glucose‐dependent volume change to facilitate glucagon release. Hypoglycemia‐triggered release of structurally unchanged glucagon from the cMN patch is demonstrated in vitro and in a rat model of type 1 diabetes (T1D). Transdermal application of the patch prevented insulin‐induced hypoglycemia in the diabetic rats. This work is the first demonstration of a glucose‐responsive glucagon‐delivery MN patch for the prevention of hypoglycemia, which has a tremendous potential to reduce the dangers of intensive insulin therapy and improve the quality of life of patients with diabetes and their caregivers.     

Insulin‐Responsive Glucagon Delivery for Prevention of Hypoglycemia

Hypoglycemia, the state of abnormally low blood glucose level, is an acute complication of insulin and sulfonylurea therapy in diabetes management. Frequent insulin dosing and boluses during daily diabetes care leads to an increased risk of dangerously low glucose levels, which can cause behavioral and cognitive disturbance, seizure, coma, and even death. This study reports an insulin‐responsive glucagon delivery method based on a microneedle (MN)‐array patch for the prevention of hypoglycemia. The controlled release of glucagon is achieved in response to elevated insulin concentration by taking advantage of the specific interaction between insulin aptamer and target insulin. Integrating a painless MN‐array patch, it is demonstrated that this insulin‐triggered glucagon delivery device is able to prevent hypoglycemia following a high‐dose insulin injection in a chemically induced type 1 diabetic mouse model.     

The Benefit of Subcutaneous Glucagon During Closed-Loop Glycemic Control in Rats With Type 1 Diabetes

Because of its prolonged action, subcutaneously administered insulin has a potential for overcorrection hypoglycemia during closed-loop glucose control. For this reason, we hypothesized that subcutaneous glucagon, whose action is faster, could lessen the risk for hypoglycemia during closed-loop control. We therefore compared insulin alone versus insulin plus glucagon in diabetic rats in a controlled closed-loop study. Both hormones were delivered by algorithms based on proportional error, derivative error, and the glucose history. Based on this algorithm, glucagon was delivered when glucose was declining and approaching a hypoglycemic level. The delivery of glucagon was largely reciprocal with the delivery of insulin. With the addition of glucagon, there was less hypoglycemia at the glucose nadir, less hyperglycemia later in the study, and lower absolute error values during these periods. We also found that for 7 days after glucagon reconstitution, commercially available glucagon retained its original ability to quickly raise glucose level. We conclude that when subcutaneous insulin delivery is accompanied by subcutaneous glucagon, glycemic control during closed-loop treatment is improved. Since its action is faster than that of insulin, glucagon may prove useful during closed-loop diabetes control.     

Glucose-Responsive Insulin and Delivery Systems: Innovation and Translation

Type 1 and advanced type 2 diabetes treatment involves daily injections or continuous infusion of exogenous insulin aimed at regulating blood glucose levels in the normoglycemic range. However, current options for insulin therapy are limited by the risk of hypoglycemia and are associated with suboptimal glycemic control outcomes. Therefore, a range of glucose-responsive components that can undergo changes in conformation or show alterations in intermolecular binding capability in response to glucose stimulation has been studied for ultimate integration into closed-loop insulin delivery or “smart insulin” systems. Here, an overview of the evolution and recent progress in the development of molecular approaches for glucose-responsive insulin delivery systems, a rapidly growing subfield of precision medicine, is presented. Three central glucose-responsive moieties, including glucose oxidase, phenylboronic acid, and glucose-binding molecules are examined in detail. Future opportunities and challenges regarding translation are also discussed.     

基于聚N-异丙基丙烯酰胺和苯硼酸的智能胰岛素递送系统的研究进展

糖尿病的治疗期于开发能够实时监测机体血糖浓度,并根据需求精确释放特定剂量胰岛素的载体材料,从而抑制高血糖的出现,同时避免低血糖的发生,以使糖尿病患者的血糖浓度趋于正常范围。温度和葡萄糖双重响应系统的研发无疑为治愈糖尿病的终极目标的实现提供了新的契机。综述了近年来以温敏性聚N-异丙基丙烯酰胺(Poly(N-isopropylacrylamide),PNIPAAm)和糖敏性苯硼酸(Phenylboronic acid,PBA)为功能主体的智能胰岛素递送系统的研究进展,包括简单构造材质(宏观凝胶和微凝胶)和复合结构材料(自组装纳米胶束、核壳式微凝胶、空心微球或微囊)等核心主题。     

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.     

Robust observer based control for plasma glucose regulation in type 1 diabetes patient using attractive ellipsoid method

This paper deals with the design of robust observer based output feedback control law for the stabilisation of an uncertain nonlinear system and subsequently apply the developed method for the regulation of plasma glucose concentration in Type 1 diabetes (T1D) patients. The principal objective behind the proposed design is to deal with the issues of intra‐patient parametric variation and non‐availability of all state variables for measurement. The proposed control technique for the T1D patient model is based on the attractive ellipsoid method (AEM). The observer and controller conditions are obtained in terms of linear matrix inequality (LMI), thus allowing to compute easily both the observer and controller gains. The closed‐loop response obtained using the designed controller avoids adverse situations of hypoglycemia and post‐prandial hyperglycemia under uncertain conditions. Further to validate the robustness of the design, closed‐loop simulations of random 200 virtual T1D patients considering parameters within the considered ranges are presented. The results indicate that hypoglycemia and post‐prandial hyperglycemia are significantly reduced in the presence of bounded (±30% ) parametric variability and uncertain exogenous meal disturbance.Inspec keywords: medical control systems, observers, uncertain systems, nonlinear control systems, robust control, control system synthesis, linear matrix inequalities, feedback, sugar, closed loop systems, diseasesOther keywords: virtual T1D patients, type 1 diabetes patients, closed‐loop simulations, uncertain conditions, post‐prandial hyperglycemia, designed controller, closed‐loop response, controller gains, linear matrix inequality, controller conditions, T1D patient model, control technique, intra‐patient parametric variation, principal objective, plasma glucose concentration, uncertain nonlinear system, robust observer based output feedback control law, attractive ellipsoid method, plasma glucose regulation     

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.     

An Organelle-Specific Nanozyme for Diabetes Care in Genetically or Diet-Induced Models

The development of nanozymes has made active impact in diagnosis and therapeutics. However, understanding of the full effects of these nanozymes on biochemical pathways and metabolic homeostasis remains elusive. Here, it is found that iron oxide nanoparticles (Fe₃O₄ NPs), a type of well-established nanozyme, can locally regulate the energy sensor adenosine 5′-monophosphate-activated protein kinase (AMPK) via their peroxidase-like activity in the acidic lysosomal compartment, thereby promoting glucose metabolism and insulin response. Fe₃O₄ NPs induce AMPK activation and enhance glucose uptake in a variety of metabolically active cells as well as in insulin resistant cell models. Dietary Fe₃O₄ NPs display therapeutic effects on hyperglycemia and hyperinsulinemia in Drosophila models of diabetes induced by genetic manipulation or high-sugar diet. More importantly, intraperitoneal administration of Fe₃O₄ NPs stimulates AMPK activities in metabolic tissues, reduces blood glucose levels, and improves glucose tolerance and insulin sensitivity in diabetic ob/ob mice. The study reveals intrinsic organelle-specific properties of Fe₃O₄ NPs in AMPK activation, glycemic control, and insulin-resistance improvement, suggesting their potential efficacy in diabetes care.     

Pyogenic liver abscess in end‐stage renal disease patients: A nationwide longitudinal study

End‐stage renal disease (ESRD) patients are more prone to infectious disease because of their immunocompromised status. However, the association between pyogenic liver abscess (PLA) and ESRD remains not clear. The aim of our study is to evaluate the incidence, risk factors, and outcomes of PLA in ESRD patients. We recruited all incident ESRD patients from the Taiwan National Health Insurance database from 1998 to 2006. The incidence rate of PLA in ESRD patients was compared with that of a randomly selected non‐ESRD control group matched for age, sex gender, Charlson comorbidity score, diabetes mellitus, and cirrhosis. Among the 57,761 incident dialysis patients, there were 538 cases of PLA. The incidence rate of PLA was 18.20 per 10,000 person‐years in the ESRD cohort and 6.34 per 10,000 person‐years in matched control cohort. The rate of PLA was significantly higher in the ESRD cohort (hazard ratio 3.63, 95% confidence interval 2.83–4.65, P < 0.001). The mortality rates of PLA were higher in the ESRD cohort than those in matched control cohort. Diabetes mellitus was an independent risk factor for mortality of PLA. Compared with non‐ESRD patients, ESRD patients have a higher risk of PLA and poorer outcomes.     

Ultrasound-triggered noninvasive regulation of blood glucose levels using microgels integrated with insulin nanocapsules

Diabetes is a serious public health problem affecting 422 million people worldwide.Traditional diabetes management often requires multiple daily insulin injections,associated with pain and inadequate glycemia control.Herein,we have developed an ultrasound-triggered insulin delivery system capable of pulsatile insulin release that can provide both long-term sustained and fast on-demand responses.In this system,insulin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocapsules are encapsulated within chitosan microgels.The encapsulated insulin in nanocapsules can passively diffuse from the nanoparticle but remain restricted within the microgel.Upon ultrasound treatment,the stored insulin in microgels can be rapidly released to regulate blood glucose levels.In a chemically-induced type 1 diabetic mouse model,we demonstrated that this system,when activated by 30 s ultrasound administration,could effectively achieve glycemic control for up to one week in a noninvasive,localized,and pulsatile manner.     

FGF‐23 and cognitive performance in hemodialysis patients

Although cognitive impairment is common in hemodialysis patients, the etiology of and risk factors for its development remain unclear. Fibroblast growth factor 23 (FGF‐23) levels are elevated in hemodialysis patients and are associated with increased mortality and left ventricular hypertrophy. Despite FGF‐23 being found within the brain, there are no prior studies assessing whether FGF‐23 levels are associated with cognitive performance. We measured FGF‐23 in 263 prevalent hemodialysis patients in whom comprehensive neurocognitive testing was also performed. The cross‐sectional association between patient characteristics and FGF‐23 levels was assessed. Principal factor analysis was used to derive two factors from cognitive test scores, representing memory and executive function, which carried a mean of 0 and a standard deviation of 1. Multivariable linear regression adjusting for age, sex, education status, and other relevant covariates was used to explore the relationship between FGF‐23 and each factor. Mean age was 63 years, 46% were women and 22% were African American. The median FGF‐23 level was 3098 RU/mL. Younger age, lower prevalence of diabetes, longer dialysis vintage, and higher calcium and phosphorus were independently associated with higher FGF‐23 levels. Higher FGF‐23 was independently associated with a lower memory score (per doubling of FGF‐23, β = ?0.08 SD [95% confidence interval, CI: ?0.16, ?0.01]) and highest quartile vs. lowest quartile (β = ?0.42 SD [?0.82, ?0.02]). There was no definite association of FGF 23 with executive function when examined as a continuous variable (β = ?0.03 SD [?0.10, 0.04]); however, there was a trend in the quartile analysis (β = ?0.28 SD [?0.63, 0.07], P = 0.13, for 4th quartile vs. 1st quartile). FGF‐23 was associated with worse performance on a composite memory score, including after adjustment for measures of mineral metabolism. High FGF‐23 levels in hemodialysis patients may contribute to cognitive impairment.     

Use of home hemoglobin A1c test kits to monitor the effectiveness of diabetes care

BACKGROUND: Periodic measurement of glycated hemoglobin (HbA1c) is highly recommended for people with diabetes to determine whether their blood glucose is adequately controlled. Quality improvement programs initiated by health plans often focus on ensuring that HbA1c is being monitored in members with diabetes. To focus improvement efforts on members with poor blood glucose control, health plans need to know which members have high HbA1c levels. Recent development of home test kits provides another opportunity for health plans to help members measure their HbA1c and to identify members with high levels. METHODS: A sample of members from two health plans who were sent HbA1c self-test kits in January 2000 participated in a telephone interview. To understand why members did or did not use self-test kits sent by their health plans, the survey focused on perceived ease of use, outcomes, and normative beliefs. RESULTS: In the group of 380 members who were interviewed, 170 (45%) used the kit. HbA1c values were > 8 mg/dl in 43%. Among the 170 who used the kit, 160 said that they would use the kit. Their most common reason for using the kit was to find out how well their blood glucose was being controlled (48%). Convenience (12%) was the next most frequent reason for using the kit. Among the 210 members who did not use the kit, 81 members said that they would not or were not sure if they would when interviewed. Their most frequent reason for not using the kit was duplication of tests done by physicians (34%). Others were too busy (12%), wanted to talk with their physician (11%), or had difficulty using the kit (11%). CONCLUSIONS: Because the majority of health plan members did not use the kit and the majority who did use the kit had HbA1c levels < 8 mg/dl, sending home test kits to members did not result in a high yield of members with elevated HbA1c levels. Physicians' support for use of the kits and efforts to make kits easier to use might increase use. Efforts to avoid duplication of physicians' measurements could make this strategy to identify members with poorly controlled levels of blood glucose more cost-effective, although health plans would not know which monitored members might benefit most from programs to improve care of diabetes.     

Glucose in the dialysate: Historical perspective and possible implications?

Hemodialysate solutions often contain high concentrations of glucose (up to 200 mg/dL). The historical reasons for the addition of glucose to the dialysate included: (1) aid in performance of ultrafiltration and (2) minimization of nutritional (caloric) losses during dialysis. However, recent experimental evidence supports the fact that exposure to high levels of glucose may be pro-inflammatory. Given the high morbidity and mortality associated with dialysis and its linkage to chronic inflammation, the routine use of glucose in the dialysate may warrant reexamination. This review examines the utility of glucose in the dialysate and discusses the potential implications on chronic inflammation in patients with end-stage renal disease. While there is currently no evidence for a casual relationship between dialysate glucose concentration and the chronic inflammation seen in ESRD, this possibility is explored.     

Outcome among patients with acute renal failure needing continuous renal replacement therapy: A single center study

Outcome of acute renal failure (ARF) and use of continuous renal replacement therapy (CRRT) have shown a consistently high mortality. (1) Evaluate the short-term patient survival. (2) Evaluate dialysis-free survival. (3) Evaluate risk factors associated with overall survival and the continued need for intermittent dialysis. We identified adults (≥18 years) needing CRRT, treated in the critical care units of Froedtert Medical and Lutheran Hospital from January 1, 2003 till December 31, 2005. Patients were divided into two major groups needing CRRT, end stage renal disease (ESRD) (chronic dialysis) and non-ESRD with ARF. Continuous renal replacement therapy was performed with an average of 2 L replacement fluid exchanges/h. Sigma stat software was used for analysis. Comparison was done for noncontinuous variables by chi-square and t test for categorical and continuous variables, respectively. A total of 110 (ESRD 24/non-ESRD 86) patients received CRRT during study period. Over all in-hospital mortality among non-ESRD patients was 63% vs. 46% for ESRD. Among non-ESRD patients who survived, 47% needed intermittent hemodialysis on intensive care unit discharge and 28% continued to need hemodialysis at last follow-up. Among non-ESRD patients alive at discharge, those who were dialysis dependent on last follow-up were older (64.5) than those who did not require dialysis on last follow-up (58.4) P=0.347. Non-ESRD patients who died were in the hospital for an average of 17.5 days compared with 29 days for those who were discharged from the hospital. Patients with ARF needing CRRT have high in-hospital mortality. A significant percentage of patients remained dialysis dependant on last follow-up.     

Safety of arteriovenous fistulae and grafts for continuous renal replacement therapy: The Michigan experience

Introduction: Arteriovenous fistula or graft (AVF/AVG) use is widely considered contraindicated for continuous renal replacement therapy (CRRT), yet insertion of hemodialysis (HD) catheters can carry high complication risk in critically ill end‐stage renal disease (ESRD) patients. Methods: Single‐center analysis of 48 consecutive hospitalized ESRD patients on maintenance HD who underwent CRRT using AVF/AVG from 2012 to 2013. Primary outcome was access‐related complications. Findings: Mean age was 60 years, 48% were male, and 88% required vasopressor support. Median duration of AVF/AVG use for CRRT was 4 days (range 1–34). Ten (21%) patients had access complications (5 bleeding, 5 infiltration, 1 thrombosis); 5 (10.4%) required catheter placement. Overall 31 (65%) patients survived to hospital discharge and AVF/AVG access was functional at the time of discharge in 29 (94%) patients. Discussion: In our experience, use of AVF/AVG for CRRT can be performed with a low serious complication rate and low risk of access loss, potentially avoiding catheter‐related complications.     

Glucose variability in maintenance hemodialysis patients with type 2 diabetes: Comparison of dialysis and nondialysis days

Introduction

Hemodialysis (HD) induces several physiological changes that can affect plasma glucose levels in patients with diabetes and in turn their glycemic control. Studies using continuous glucose monitoring (CGM) to assess glucose variations on dialysis days compared with nondialysis days report conflicting results. Here, we used CGM to examine glucose variations induced by HD in patients with type 2 diabetes.

Methods

Patients with type 2 diabetes undergoing maintenance HD were included. CGM (Ipro2®, Medtronic) was performed at baseline and Week 4, 8, 12, and 16 for up to 7 days at each visit. CGM profiles on days where participants received HD were compared with days without HD using a linear mixed model.

Findings

Twenty-seven patients were included. The median number of CGM days performed was 8 (interquartile range [IQR] 6–10) for dialysis days and 16 (IQR 12–17) for nondialysis days. The median sensor glucose was 9.4 (95% confidence interval [CI] 8.8–10.2) mmol/L on dialysis days compared with 9.5 (95% CI 8.9–10.2) mmol/L on nondialysis days (p = 0.58). Nocturnal mean sensor glucose was higher on dialysis days compared with nondialysis days: 8.8 (95% CI 8.0–9.6) mmol/L versus 8.4 (95% CI 7.7–9.2) mmol/L (p = 0.029).

Discussion

Similar median sensor glucose values were found for days on and off HD. Nocturnal glucose levels were modestly increased on dialysis days. Our findings indicate that antidiabetic treatment does not need to be differentiated on dialysis versus nondialysis days in patients with type 2 diabetes undergoing maintenance HD.     

Non-invasive Glucose Measurements Using Wavelength Modulated Differential Photothermal Radiometry (WM-DPTR)

Wavelength-modulated differential laser photothermal radiometry (WM-DPTR) is introduced for potential development of clinically viable non-invasive glucose biosensors. WM-DPTR features unprecedented glucose-specificity and sensitivity by combining laser excitation by two out-of-phase modulated beams at wavelengths near the peak and the baseline of a prominent and isolated mid-IR glucose absorption band. Measurements on water?Cglucose phantoms (0 to 300?mg/dl glucose concentration) demonstrate high sensitivity to meet wide clinical detection requirements ranging from hypoglycemia to hyperglycemia. The measurement results have been validated by simulations based on fully developed WM-DPTR theory. For sensitive and accurate glucose measurements, the key is the selection and tight control of the intensity ratio and the phase shift of the two laser beams.     

Cardiac autonomic dysfunction in hemodialysis patients: The value of heart rate turbulence

Patients with end-stage renal disease (ESRD) are likely to have cardiac autonomic dysfunction, which is related with an increased risk of sudden death. The aim of this study is to detect cardiac autonomic dysfunction in patients with ESRD and to evaluate the possible acute effects of hemodialysis (HD) on cardiac autonomic functions measured by heart rate variability (HRV) and heart rate turbulence (HRT). Thirty-one (mean age 50 ± 13 years, 15 males) with ESRD on regular HD program and 31 healthy volunteers (mean age 51 ± 12 years, 15 males) were included in the study. Twenty-four-hour ambulatory electrocardiogram recordings were taken from the subjects before and after HD and from the control group. Heart rate variability and HRT parameters were calculated from these recordings. All of the HRV and HRT parameters were found to be significantly blunted in patients in comparison with healthy individuals. There were significant differences in HRV after HD, but similar differences were not observed in HRT parameters. Cardiac autonomic functions were significantly altered in patients with ESRD. Heart rate turbulence parameters seemed to be less affected from HD and may be more useful in the evaluation of cardiac autonomic functions in the ESRD population.