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The UV absorption spectrum of all-trans-octatetraene is reinvestigated theoretically, focussing on the strongly dipole-allowed 1 A g – 1 B u transition. The dynamical calculations rely on ab initio multistate CASPT2 (MS-CASPT2) computations of the underlying potential energy surfaces and coupling elements, and the multiconfiguration time-dependent Hartree (MCTDH) method for solving the time-dependent Schrödinger equation for the nuclear motion. The vibronic structure of the absorption band near 2700 Å is well reproduced, better than ever before by a purely ab initio approach. The C–C single bond and C = C double bond stretching modes dominate the vibrational structure of the transition. While the latter resembles nearly harmonic motion on weakly coupled potential energy surfaces, the time-dependent calculations reveal a subpicosecond electronic population transfer from the 1 B u state to the lower-lying 2 A g state proceeding on a time scale of ∼ 50 fs . The details of this internal conversion process and its relation to the conical intersection between the two excited states are discussed, paying particular attention to the impact of the 1 B u – 2 A g energy gap on the dynamics. [ABSTRACT FROM AUTHOR]

We reviewed a number of prospective randomized and multiple retrospective cohort studies of different dialysis prescriptions: longer dialysis time, at a frequency of at least three times a week, or a frequency of daily hemodialysis with a shorter dialysis time. Interestingly, the retrospective analyses have generally found significant survival benefits in the intensive dialysis groups, whereas more modest effects were observed in the prospective randomized controlled trials. The reason for this discrepancy may be related to the retrospective nature of the studies and possible selection bias; for example, the patients who were prescribed more frequent dialysis may have had more difficulties with volume control or high blood pressure. In contrast, the randomized controlled trials of increased dialysis frequency, which have shown indirect and modest benefits in complex coprimary end points, have small sample sizes and are plagued with difficulties in recruitment and compliance with the randomly allocated more frequent dialysis. This review, which attempts to balance the potential benefits of more frequent dialysis with the burden on the patient's lifestyle, an increased risk of access malfunction, as well as societal costs of such intensive dialysis prescriptions, concludes in favor of the conventional three times per week dialysis (at a minimum) but at longer dialysis times than is currently prescribed based on the Kt/Vurea metric alone. [ABSTRACT FROM AUTHOR]

Eighty-two percent (82%) of patients initiating hemodialysis in the United States in 2006 did so with a catheter as the functioning access. Even in patients who have been followed by nephrologists for 6 months or more, 74% of patients initiated dialysis with a catheter. This is a multifactoral problem that requires attention and solutions from all stakeholders, including the nephrologist, the vascular surgeon, the hospital, and the insurance industry, as well as the patient and family. We propose a series of specific proposals that include a process for the timely referral and timely placement of a permanent access based on the patient's estimated or measured glomerular filtration rate (GFR), and a ‘pay-for-performance’ measure for vascular surgeons and nephrologists who admit patients with functional permanent accesses; such pay for performance would place a higher value for patients who are admitted with a functional arteriovenous (AV) fistula than for patients who are admitted with an AV graft. We also propose that hospitals develop a less permissive process for placement of PICC (peripherally inserted central catheters) lines in patients with GFR <60 ml/min and to consider surgery for access placement as ‘urgent’. Finally, a more proactive educational process for patients and their families, including an ‘informed non-consent’ for patients who defer placement of a permanent access needs to be considered. The morbidity, mortality, and health-care costs associated with prolonged catheter use mandate urgent attention to this problem. [ABSTRACT FROM AUTHOR]

Suggests possible ways to enhance the partnership between the United States Centers for Disease Control and Prevention (CDC) and the dialysis community. Consolidation of dialysis-related recommendations of the CDC; Designation of representatives from dialysis providers to the infection control contact for the CDC.

Hemodialysis access failure: A call to action. Recent evidence suggests that the cost as well as the morbidity associated with the maintenance of hemodialysis access is increasing rapidly; currently, the cost exceeds 1 billion dollars and access related hospitalization accounts for 25% of all hospital admissions in the U.S.A. This increase in cost and morbidity has been associated with several epidemiological trends that may contribute to access failure. These include late patient referral to nephrologists and surgeons, late planning of vascular access as well as a shift from A-V fistulaes to PTFE grafts and temporary catheters, which have a higher failure rate. The reasons for this shift in the types of access is multifactorial and is not explained by changes in the co-morbidities of patients presenting to dialysis. Surgical preference and training also appear to play an important role in the large regional variation and patency rate of these PTFE grafts. We propose a program for early placement of A-V fistulae, a continuous quality improvement, multidisciplinary program to monitor access outcome, the development of new biomaterials, and a research plan to investigate pharmacological intervention to reduce development of stenosis and clinical interventions to treat those that do develop, prior to thrombosis. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding a previously published article which discussed findings that hemodialysis care in private not-for-profit centers was associated with a lower risk of mortality. Number of studies the authors excluded in their report.

Editorial. Comments on the study by Fleischman and colleagues which showed that low body mass index (BMI) is associated with increased risk of hospitalization and mortality, even after adjusting for demographic attributes and nutritionally-associated serum markers. Additional protective effect of having 'excess' nutrition, particularly in the Afro-American patient; Hemodialysis nutrition; ESRD.

The dynamical processes following photoexcitation of all -trans 2,4,6-octatriene to the two lowest singlet excited states are investigated theoretically, from two different points of view. The S 1 - S 0 photoisomerization is characterized with a focus on structural aspects (stationary points and reactive modes), while for the UV–visible spectrum, arising from excitation to the S 2 state, nonadiabatic quantum dynamics calculations with four planar degrees of freedom are performed. The underlying electronic structure data are obtained from CASSCF and MS-CASPT2 ab initio computations, the quantum dynamical calculations rely on the Multiconfiguration Time-Dependent Hartree (MCTDH) method. The observed envelope of the UV–visible spectrum is well reproduced and the substantial broadness of the spectral features related to a nonradiative S 2 -S 1 transition proceeding within few tens of femtoseconds. The vertical excitation energy from the A g to the B u state shows a red-shift (∼0.2 eV with the cc-pVTZ basis set) with reference to the all -trans hexatriene system. This affects the S 2 -S 1 nonradiative decay, while the methylation of the terminal carbon atoms seems to have a minor influence on the photo-isomerization path. [ABSTRACT FROM AUTHOR]

Background: The mortality rate among patients with acute renal failure remains high, and the role of the biocompatibility of the dialysis membrane in the resolution of this disorder is not known. Methods: We prospectively studied 72 patients with acute renal failure who required hemodialysis and assigned them to two treatment groups. One group underwent dialysis with the widely used cuprophane dialysis membrane, which activates the complement system and leukocytes, and the other group underwent dialysis with a synthetic polymethyl methacrylate membrane, which has a more limited effect on complement and leukocytes. Scores on the Acute Physiology, Age, and Chronic Health Evaluation (APACHE II) were calculated at the initiation of dialysis. Survival and the recovery of renal function were determined with the use of proportional-hazards and exact logistic-regression analyses. Results: When dialysis was initiated, the patients in the two groups were similar in terms of age, APACHE II scores, the prevalence of oliguria, and biochemical indexes of renal failure. Twenty-three of the 37 patients (62 percent) in the group undergoing dialysis with the polymethyl methacrylate membrane recovered renal function, as compared with 13 of the 35 patients (37 percent) in the group undergoing dialysis with the cuprophane membrane (P = 0.04 after adjustment for the APACHE II score). The median number of dialysis treatments required before the recovery of renal function was 5 in the former group and 17 in the latter group (P = 0.02). Twenty-one patients (57 percent) undergoing dialysis with the polymethyl methacrylate membrane survived, as compared with 13 patients (37 percent) undergoing dialysis with the cuprophane membrane (P = 0.11). Of the 20 patients in each group who initially had nonoliguric acute renal failure, the survival rates were 80 percent with the polymethyl methacrylate membrane and 40 percent with the cuprophane membrane (P = 0.01). Conclusions: Among patients with acute renal failure requiring hemodialysis, the use of the polymethyl methacrylate membrane, as compared with the cuprophane membrane, resulted in improved recovery of renal function. (N Engl J Med 1994;331:1338-42.) [ABSTRACT FROM AUTHOR]

The role of the dialysis unit Medical Director has evolved over time to an expanded set of roles from one that used to be strictly “medical” to one that is more “managerial.” Physicians providing these Medical Director services are facing increasing demands for a leadership role regarding clinical quality improvement and measurement of performance in core areas of care within the dialysis program. The dialysis Medical Director is asked to lead in group decision-making, in analyzing core process and patient outcomes and in stimulating a team approach to Continuous Quality Improvement (CQI) and patient safety. For the end-stage renal disease program, national quality expectations in dialysis care have stimulated the dialysis providers to measure, report and respond consistently in an effort to provide a higher level of cost-efficient care. Medical Directors are usually contractually linked to the dialysis programs for which they provide oversight and their contracts are explicit about the relationship they maintain and the role they are expected to play within dialysis companies (often called “provider organizations”). The evolution of the Medical Director role has led to a close relationship between the company that provides the dialysis services and the physician providing the medical oversight. [ABSTRACT FROM AUTHOR]

Uremic malnutrition is a predictor of death independent of inflammatory status.Background.Several studies have pointed out the influence of nutritional parameters and/or indices of inflammation on morbidity and mortality. Often, these conditions coexist, and the relative importance of poor nutritional status and chronic inflammation in terms of predicting clinical outcomes in chronic hemodialysis (CHD) patients has not been clarified.Methods.We undertook a prospective cohort study analyzing time-dependent changes in several established nutritional and inflammatory markers, and their influence on mortality in 194 CHD patients (53% male, 36% white, 30% with diabetes mellitus, mean age 55.7± 15.4 years) throughout a 57-month period. Serial measurements of serum concentrations of albumin, prealbumin, creatinine, transferrin, cholesterol, and C-reactive protein (CRP), as well as normalized protein catabolic rate, postdialysis weight, and phase angle and reactance by bioelectrical impedance analysis were performed every 3 months. Clinical outcomes were simultaneously assessed using indicators of mortality.Results.Serum albumin, serum prealbumin, serum creatinine, and phase angle were significant predictors of all-cause mortality, even after adjustment for serum CRP concentrations. Serum CRP concentrations were not significantly associated with mortality. Serum albumin concentrations and phase angle were also independent predictors of cardiovascular deaths in the multivariate model.Conclusion.The nutritional status of CHD patients predicts mortality independent of concomitant presence or absence of inflammatory response. Prevention of, and timely intervention to treat uremic malnutrition by suitable means are necessary independent of the presence and/or therapy of inflammation in terms of improving clinical outcomes in CHD patients. [ABSTRACT FROM AUTHOR]

Urea volume of distribution exceeds total body water in patients with acute renal failure.. Background: An accurate estimate of volume of distribution of urea (V[sub urea]) is critically important to guide the prescription of therapy and the quantification of delivered dialysis dose in patients with chronic and acute renal failure (ARF). While V[sub urea] has been shown to be substantially the same as total body water (TBW) in other patient populations, this relationship has not been adequately studied in detail in ARF patients. Methods: To evaluate this question, we undertook a systematic study of these parameters in a cohort of 28 patients with ARF to analyze methods of estimating V[sub urea] and TBW using blood-based kinetic data, anthropometric data and bioelectrical impedance analysis (BIA). Results: The results show that V[sub urea] estimated by double-pool Kt/V (67.9 ± 19.2 L) and by equilibrated Kt/V (61.2 ± 13.6 L) were statistically significantly higher than V[sub urea] determined by single-pool Kt/V (55.3 ± 12.9 L; difference of 16% and 11%, respectively). Determination of TBW by anthropometric measurements (Watson, 42.5 ± 7.0 L; Hume-Weyer, 43.6 ± 7.1 L; Chertow, 46.8 ± 8.1 L) yielded significantly lower measures compared to TBW determined by physiological formulae and by BIA (51.1 ± 11.6 L and 51.1 ± 13.3 L, respectively). Most importantly, all measures of V[sub urea] by blood-based kinetics exceeded TBW measurements by any method (7% to 50% difference). Conclusion: Our results suggest that in terms of useful guidelines to prescribe a specific dose of dialysis in patients with acute renal failure, estimates of TBW cannot be used as a surrogate for V[sub urea] in determining dialysis adequacy. [ABSTRACT FROM AUTHOR]

Examines angiotensin-converting enzyme inhibitors in hemodialysis membranes. Acute reactions to cellulosic membranes; Pathogenesis of PAN-Associated anaphylactoid reaction; Clinical features of membrane-induced reactions associated ACE-I; Prevention and treatment of anaphylactoid reactions.

Patient selection and training is arguably the most important step toward building a successful home hemodialysis (HD) program. We present a step-by-step account of home HD training to guide providers who are developing home HD programs. Although home HD training is an important step in allowing patients to undergo dialysis in the home, there is a surprising lack of systematic research in this field. Innovations and research in this area will be pivotal in further promoting a higher acceptance rate of home HD as the renal replacement therapy of choice. [ABSTRACT FROM AUTHOR]

Patient selection and training is arguably the most important step toward building a successful home hemodialysis ( HD) program. We present a step-by-step account of home HD training to guide providers who are developing home HD programs. Although home HD training is an important step in allowing patients to undergo dialysis in the home, there is a surprising lack of systematic research in this field. Innovations and research in this area will be pivotal in further promoting a higher acceptance rate of home HD as the renal replacement therapy of choice. [ABSTRACT FROM AUTHOR]

Mortality rates for maintenance hemodialysis patients are much higher than the general population and are even greater soon after starting dialysis. Here we analyzed mortality patterns in 86,886 patients in 11 countries focusing on the early dialysis period using data from the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study of in-center hemodialysis. The primary outcome was all-cause mortality, using time-dependent Cox regression, stratified by study phase adjusted for age, sex, race, and diabetes. The main predictor was time since dialysis start as divided into early (up to 120 days), intermediate (121-365 days), and late (over 365 days) periods. Mortality rates (deaths/100 patient-years) were 26.7 (95% confidence intervals 25.6-27.9), 16.9 (16.2-17.6), and 13.7 (13.5-14.0) in the early, intermediate, and late periods, respectively. In each country, mortality was higher in the early compared to the intermediate period, with a range of adjusted mortality ratios from 3.10 (2.22-4.32) in Japan to 1.15 (0.87-1.53) in the United Kingdom. Adjusted mortality rates were similar for intermediate and late periods. The ratio of elevated mortality rates in the early to the intermediate period increased with age. Within each period, mortality was higher in the United States than in most other countries. Thus, internationally, the early hemodialysis period is a high-risk time for all countries studied, with substantial differences in mortality between countries. Efforts to improve outcomes should focus on the transition period and the first few months of dialysis. [ABSTRACT FROM AUTHOR]

Background The relationship between severity of depressive symptoms reported by incident dialysis patients and first-year outcomes is not known. Methods We evaluated the association between self-report of depressive symptoms in incident hemodialysis patients admitted at Fresenius Medical Care North America facilities between 1 January and 31 December 2006 and mortality or withdrawal from dialysis for up to 1 year after the initial survey. The impact of depression scores calculated from two Short Form-36 (SF-36) questionnaires was determined independently of the mental and physical component scores, case-mix and laboratory variables using stepwise Cox models. Results We received 6415 SF-36 responses within 46 ± 24 days of first dialysis from a cohort with a mean age of 62.3 ± 15.2 years; 58% were diabetic, 45% were female and 69% were Caucasian. A 1-point increase in depression score was associated with unadjusted hazard ratio (HR) of 1.09 (1.03, 1.15) for mortality and 1.15 (1.05, 1.26) for withdrawal from dialysis. After adjustment, a 1-point increase in depression score had a mortality HR of 1.08 (1.01, 1.14) and for withdrawal 1.19 (1.08, 1.31). Conclusions Depressive symptoms reported within the first 90 days of dialysis were associated with greater dialysis withdrawal and mortality risk over the succeeding year. Whether further evaluation for and treatment of depression during this early vulnerable period may improve symptoms, increase survival and decrease premature withdrawal from dialysis requires confirmation in prospective clinical trials. [ABSTRACT FROM PUBLISHER]

To compare the relative effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing cardiovascular mortality in chronic hemodialysis patients, we conducted an observational analysis of all patients initiated on ACEI or ARB therapy undergoing chronic hemodialysis at a large dialysis provider. Survival curves with mortality hazard ratios (HRs) were generated using the Kaplan-Meier method and Cox regression. Outcomes were compared using inverse probability of treatment weighting and propensity score matching. Over 6 years, 22,800 patients were newly initiated on an ACEI and 5828 on an ARB after at least 60 days of chronic hemodialysis. After adjustment for baseline cardiovascular risk factors, there was no significant difference in the risk of cardiovascular, all-cause, or cerebrovascular mortality in patients initiated on an ARB compared with an ACEI (HR of 0.96). A third of 28,628 patients, newly started on an ACEI or ARB, went on to another antihypertensive medication in succession. After adjustment for risk factors, 701 patients initiated on combined ACEI and ARB therapy (HR of 1.45) or 6866 patients on ACEI and non-ARB antihypertensive agent (HR of 1.27) were at increased risk of cardiovascular death compared with 1758 patients initiated on an ARB and non-ACEI antihypertensive therapy. Thus, an ARB, in combination with another antihypertensive medication (but not an ACEI), may have a beneficial effect on cardiovascular mortality. As observational studies may be confounded by indication, even when adjusted, randomized clinical trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The International Quotidian Dialysis Registry (IQDR) is a global initiative designed to study practices and outcomes associated with the use of hemodialysis (HD) regimens of increased frequency and/or duration. The IQDR grew out of the initiative that lead to the randomized prospective studies of nocturnal HD and short hours daily dialysis vs. conventional thrice weekly HD that are conducted by the Frequent Hemodialysis Network sponsored by the National Institutes of Health. These 2 separate studies are drawing to a close and the first results are expected to be reported later this year. These studies use surrogate outcomes for their primary endpoints as they are not powered to look at outcomes of mortality and hospitalization. The IQDR attempts to aggregate long-term follow-up data from centers utilizing alternative HD regimens worldwide and will have adequate statistical power to examine those important outcomes. To date, the IQDR has enrolled patients from Canada, the United States, Australia, New Zealand, and France and has linked with commercial databases and national registries. This sixth annual report of the IQDR describes: (1) An update on the governance structure; (2) The recommendations made at the first general meetings of the IQDR Scientific Committee and Advisory Board; (3) The status of those recommendations; (4) A summary of current data sources and participating registries; (5) The status of recruitment to date; (6) The creation of a specific Canadian IQDR data set and; (7) The current research agenda. [ABSTRACT FROM AUTHOR]

Dialysis patients have a greater number of hospitalization events compared to patients without renal failure. Here we studied the relationship between different post-discharge interventions and repeat hospitalization in over 126,000 prevalent hemodialysis patients to explore outpatient strategies that minimize the risk of repeat hospitalization. The primary outcome was repeat hospitalization within 30 days of discharge. Compared to pre-hospitalization values, the levels of hemoglobin, albumin, phosphorus, calcium, and parathyroid hormone and weight were significantly decreased after hospitalization. Using covariate-adjusted models, those patients whose hemoglobin was monitored within the first 7 days after discharge, followed by modification of their erythropoietin dose had a significantly reduced risk for repeat-hospitalization when compared to the patients whose hemoglobin was not checked, nor was the dose of erythropoietin changed. Similarly, administration of vitamin D within the 7 days following discharge was significantly associated with reduced repeat hospitalization when compared to patients on no vitamin D. Therefore, it appears that immediate re-evaluation of anemia management orders and resumption of vitamin D soon after discharge may be an effective way to reduce repeat hospitalization.Kidney International (2009) 76, 331–341; doi:10.1038/ki.2009.199; published online 10 June 2009 [ABSTRACT FROM AUTHOR]

The International Quotidian Dialysis Registry (IQDR) is a global initiative designed to study practices and outcomes associated with the use of hemodialysis regimens of increased frequency and/or duration. Several small studies suggest that compared with conventional hemodialysis (HD), short-daily, nocturnal, and long conventional HD regimens may improve surrogate endpoints and quality of life. However, methodologically robust comparisons on hard outcomes are sorely lacking. The IQDR represents the first-ever attempt to aggregate long-term follow-up data from centers utilizing alternative HD regimens worldwide, and will have adequate statistical power to examine the effects of these regimens on multiple clinical endpoints, including mortality. To date, the IQDR has enrolled patients from Canada, the United States, Australia, and New Zealand, with plans in place to begin linking with additional commercial databases and national registries. This fifth annual report of the IQDR describes (1) a proposed governance structure that will facilitate international collaboration, stakeholder input and funding; (2) data sources and participating registries; (3) recruitment to date and patient baseline characteristics; and (4) an agenda for future research. [ABSTRACT FROM AUTHOR]

Alternative hemodialysis (HD) schedules, including short-daily and nocturnal HD, continue to proliferate, with the hope of offering improved patient outcomes. Three nights per week and every other night, nocturnal HD are now being provided to more patients worldwide, both at home and in-center. However, alternative HD schedules are still experimental in most centers, and studies establishing the efficacy of these therapies with respect to major clinical outcomes are needed. Endorsed by the National Institutes of Health, the International Quotidian Dialysis Registry is an international collaboration that was established in 2002 to prospectively study large numbers of patients treated with alternate HD schedules. The Registry will ultimately allow alternate HD modalities to be compared to conventional thrice-weekly HD with respect to clinical endpoints, including mortality, using a prospective cohort study. To date, the Registry has enrolled 182, 1193, and 740 subjects from Canada, the United States, and Australia, respectively. This report is the fourth annual update and describes recruitment progress, baseline characteristics of enrolled patients, and worldwide prescription patterns. [ABSTRACT FROM AUTHOR]

Biomarkers of inflammation, especially C-reactive protein (CRP), have been consistently shown to predict poor outcomes in chronic hemodialysis (CHD) patients. However, the determinants of CRP and the value of its monitoring in CHD patients have not been well defined. We conducted a retrospective cohort study to evaluate possible determinants of the inflammatory response in CHD patients with a focus on dialysis catheter utilization. Monthly CRP were measured in 128 prevalent CHD patients (mean age 56.6 years [range 19–90], 68% African Americans, 39% diabetics [DM]) over a mean follow-up of 12 months (range 2–26 months). There were a total of 2405 CRP measurements (median 5.7 mg/L; interquartile range [IQR] 2.4–16.6 mg/L). The presence of a dialysis catheter (p<0.002), cardiovascular disease (p=0.01), male gender (p=0.005), higher white blood cell count (p<0.0001), elevated phosphorus (p=0.03), and lower cholesterol (p=0.02) and albumin (p<0.0001) concentrations were independent predictors of elevated CRP in the multivariate analysis. Additionally, CRP levels were significantly associated with the presence of a catheter, when comparing the levels before and after catheter insertion (p=0.002) as well as before and after catheter removal (p=0.009). Our results indicate that the presence of a hemodialysis catheter is an independent determinant of an exaggerated inflammatory response in CHD patients representing a potentially modifiable risk factor. [ABSTRACT FROM AUTHOR]

Urea space and total body water measurements by stable isotopes in patients with acute renal failure. Background. Knowledge of urea volume of distribution (Vurea) in patients with acute renal failure (ARF) is critical in order to prescribe and monitor appropriate dialytic treatment. We have recently shown that in ARF patients, Vurea estimation by urea kinetic modeling is significantly higher than total body water (TBW) by anthropometric estimation. However, these estimates of Vurea and TBW have not been validated by isotopic methods, considered as reference measurement standards. Methods. In this study, we measured Vurea by [13C]urea and TBW by deuterium oxide (D2O) in 21 patients with ARF (14 males, 7 females, age 62.0 ± 10.6 years old, 83% Caucasian, 17% African American) at three different centers. These measurements were compared to TBW estimates from anthropometric and bioelectrical impedance (BIA) measurements. Results. Our results show that Vurea by [13C]urea (51.0 ± 11.7 L) is significantly higher than TBW estimated by all other methods (TBW by D2O: 38.3 ± 9.8 L, P < 0.001; TBW by BIA: 45.7 ± 15.7 L, P= 0.08; TBW by Watson formula: 38.3 ± 7.3 L, P < 0.001; TBW by Chertow formula: 39.3 ± 7.8 L, P= 0.002, all versus Vurea). Despite significant overestimation of the absolute value and considerable variation, Vurea significantly correlated with TBW by BIA ( r= 0.66, P < 0.01) and TBW by D2O ( r= 0.5, P= 0.04). There was also significant correlation between D2O and BIA determined TBW ( r= 0.8, P < 0.001). Conclusion. In terms of useful guidelines to prescribe a specific dose of dialysis in patients with ARF, conventional estimates of TBW as surrogates for Vurea should be used with caution. We propose that these conventional estimates of TBW should be increased by approximately 20% (a factor of 1.2) to avoid significant underdialysis. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of mortality in uremic patients. In large cross-sectional studies of dialysis patients, traditional cardiovascular risk factors such as hypertension and hypercholesterolemia have been found to have low predictive power, while markers of inflammation and malnutrition are highly correlated with cardiovascular mortality. However, the pathophysiology of the disease process that links uremia, inflammation, and malnutrition with increased cardiovascular complications is not well understood. We hereby propose the hypothesis that increased oxidative stress and its sequalae is a major contributor to increased atherosclerosis and cardiovascular morbidity and mortality found in uremia. This hypothesis is based on studies that conclusively demonstrate an increased oxidative burden in uremic patients, before and particularly after renal replacement therapies, as evidenced by higher concentrations of multiple biomarkers of oxidative stress. This hypothesis also provides a framework to explain the link that activated phagocytes provide between oxidative stress and inflammation (from infectious and non-infectious causes) and the synergistic role that malnutrition (as reflected by low concentrations of albumin and/or antioxidants) contributes to the increased burden of cardiovascular disease in uremia. We further propose that retained uremic solutes such as beta-2 microglobulin, advanced glycosylated end products (AGE), cysteine, and homocysteine, which are substrates for oxidative injury, further contribute to the pro-atherogenic milieu of uremia. Dialytic therapy, which acts to reduce the concentration of oxidized substrates, improves the redox balance. However, processes related to dialytic therapy, such as the prolonged use of catheters for vascular access and the use of bioincompatible dialysis membranes, can contribute to a pro-inflammatory and pro-oxidative state and thus to a pro-atherogenic state. Anti-oxidative therapeutic... [ABSTRACT FROM AUTHOR]

Inflammatory signals associated with hemodialysis. Background. Inflammation is highly prevalent in chronic hemodialysis patients. Because hemodialysis involves the contact of blood with “foreign” surfaces, and the documented activation of several humoral and cellular pathways during the procedure, the hemodialysis procedure has been suggested as a potential source of inflammation in this patient population. Earlier studies did not provide clear-cut evidence of the potential contribution of the hemodialysis procedure to inflammation, as assessed by markers of inflammation such as cytokine levels and acute-phase protein production. Methods. Nine patients were studied using primed-constant infusion of l-(l-13 C) leucine 2 hours before, during, and 2 hours after a single hemodialysis session. We evaluated the effects of hemodialysis on induction of interleukin-6 (IL-6) production as well as the fractional synthetic rates (FSR) of albumin and fibrinogen, two well-known acute-phase proteins. Results. During hemodialysis, albumin FSR and fibrinogen FSR increased significantly compared to the measurements obtained during baseline period. During this period, albumin and fibrinogen FSR increased 64% and 34%, respectively, compared to baseline (P < 0.05). While the increase in IL-6 concentration was modest during hemodialysis (14%), the levels further increased at the end of the 2-hour post-hemodialysis period (68% higher compared to baseline, P < 0.05). Fibrinogen FSR also demonstrated a further increase during the post-dialysis period (17% higher compared to the intradialytic period and 58% higher compared to baseline), while albumin FSR stabilized during this period. Conclusions. The results provide clear evidence of hemodialysis-induced inflammatory response. The process is most notable during the 2-hour post-hemodialysis period. [ABSTRACT FROM AUTHOR]

Therapeutic effects of oral nutritional supplementation during hemodialysis. Background. Protein-calorie malnutrition is common in chronic hemodialysis (CHD) patients and correlates with morbidity and mortality in these patients. There are limited trials evaluating the efficacy of oral nutritional supplementation in malnourished CHD patients. Methods. Eighty-five CHD patients with evidence of malnutrition were included in this prospective study. Patients were followed for a 3-month baseline period during which they received conventional nutrition counseling. This was followed by an intervention period, during which an oral nutritional supplement specifically formulated for CHD patients was given over a period of 6 months. An important element of this study was that the nutritional supplement was provided during dialysis to ensure compliance. Serial measurements of nutritional parameters including concentrations of serum albumin, prealbumin, transferrin as well as body mass index (BMI) and subjective global assessment (SGA) were obtained during the 9-month period. Results. The nutritional parameters did not change during the 3-month baseline period. Following administration of oral supplementation during hemodialysis, there were significant increases in concentrations of serum albumin (from 3.33 ± 0.32 g/dL at baseline, to 3.65 ± 0.26 g/dL at month 6, P < 0.0001) and serum prealbumin (from 26.1 ± 8.6 mg/dL at baseline, to 30.7 ± 7.4 mg/dL at month 6, P = 0.002). Mean SGA score increased 14% by the end of the study (P = 0.023). Although BMI and estimated dry weight increased also, these changes were not statistically significant. Serum transferrin did not change during the study period. Conclusion. Oral nutritional supplementation given during hemodialysis improves nutritional markers in malnourished CHD patients. [ABSTRACT FROM AUTHOR]

Presents a study which examined protein and energy homeostasis during hemodialysis in several chronic hemodialysis (CHD) patients with and without intradialytic parenteral nutrition (IDPN). Factors that predispose end-stage renal disease patients on chronic hemodialysis therapy to protein calorie malnutrition; Results of the administration of IDPN; Strategies to improve dietary nutrient intake in CHD patients.

Decreased dietary protein intake and hemodialysis-associated protein catabolism are among several factors that predispose chronic hemodialysis (CHD) patients to protein calorie malnutrition. Since attempts to increase protein intake by dietary counseling are usually ineffective, intradialytic parenteral nutrition (IDPN) has been proposed as a potential therapeutic approach in malnourished CHD patients. In this study, we examined protein and energy homeostasis during hemodialysis in seven CHD patients at two separate hemodialysis sessions, with and without IDPN administration. Patients were studied 2 hours before, during, and 2 hours following a hemodialysis session, using a primed constant infusion of L-(1-(13)C) leucine and L-(ring-(2)H(5)) phenylalanine. Our results showed that IPDN promoted a large increase in whole-body protein synthesis and a significant decrease in whole-body proteolysis, along with a significant increase in forearm muscle protein synthesis. The net result was a change from an essentially catabolic state to a highly positive protein balance, both in whole-body and forearm muscle compartments. We conclude that the provision of calories and amino acids during hemodialysis with IDPN acutely reverses the net negative whole-body and forearm muscle protein balances, demonstrating a need for long-term clinical trials evaluating IDPN in malnourished CHD patients. [ABSTRACT FROM AUTHOR]

Vascular access blood flow monitoring reduces access morbidity and costs. Background. Vascular access morbidity results in suboptimal patient outcomes and costs more than $8000 per patient-year at risk, representing approximately 15% of total Medicare expenditures for ESRD patients annually. In recent years, the rate of access thrombosis has improved following the advent of vascular access blood flow monitoring (VABFM) programs to identify and treat stenosis prior to thrombosis. To define further both the clinical and financial impact of such programs, we used the ultrasound dilution method to study the effects of VABFM on thrombosis-related morbid events and associated costs, compared with both dynamic venous pressure monitoring (DVPM) and no monitoring (NM) in arteriovenous fistulas (AVF) and grafts. Methods. A total of 132 chronic hemodialysis patients were followed prospectively for three consecutive study phases (I, 11 months of NM; II, 12 months of DVPM; III, 10 months of VABFM). All vascular access-related information (thrombosis rate, hospitalization, angiogram, angioplasty, access surgery, thrombectomy, catheter placement, missed treatments) was collected during the three study periods. Results. During the three study phases, graft thrombosis rate was reduced from 0.71 (phase I), to 0.67 (phase II), to 0.16 (phase III) events per patient-year at risk (P < 0.001 phase III vs. phases I and II). Similarly, hospital days, missed treatments, and catheter use related to thrombotic events were significantly reduced during phase III compared to phases I and II. Hospital days related to vascular access morbidity and adjusted for patient-year at risk were 1.8, 1.6, and 0.4 and missed dialysis treatments were 0.98, 0.86, and 0.26 treatments per patient-year at risk for phases I, II, and III, respectively (P < 0.001 for phase III vs. phases I and II). Catheter use was also significantly reduced during phases II and III, from 0.29 (phase I) to 0.17 and further to... [ABSTRACT FROM AUTHOR]

Investigates the role of transforming growth factor-beta in the pathogenesis of dialysis-related to amyloidosis. Termination of inflammatory response; Release of proinflammatory cytokines through macrophage activation; Measurement of endotoxin levels.

Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: A prospective study. Background. Numerous studies suggest a strong association between nutrition and clinical outcome in chronic hemodialysis (CHD) patients. Nevertheless, the pathophysiological link between malnutrition and morbidity remains to be clarified. In addition, recent evidence suggests that nutritional indices may reflect an inflammatory response, as well as protein–calorie malnutrition. In this study, we prospectively assessed the relative importance of markers of nutritional status and inflammatory response as determinants of hospitalization in CHD patients. Methods. The study consisted of serial measurements of concentrations of serum albumin, creatinine, transferrin, prealbumin, C-reactive protein (CRP), and reactance values by bioelectrical impedance analysis (BIA) as an indirect measure of lean body mass every 3 months over a period of 15 months in 73 CHD patients. Outcome was determined by hospitalizations over the subsequent three months following each collection of data. Results. Patients who required hospitalization in the three months following each of the measurement sets had significantly different values for all parameters than patients who were not hospitalized. Thus, serum albumin (3.93 ± 0.39 vs. 3.74 ± 0.39 g/dl), serum creatinine (11.0 ± 3.7 vs. 9.1 ± 3.5 mg/dl), serum transferrin (181 ± 35 vs. 170 ± 34 mg/dl), serum prealbumin (33.6 ± 9.2 vs. 30.0 ± 10.1 mg/dl), and reactance (50.4 ± 15.6 vs. 43.0 ± 13.0 ohms) were higher for patients not hospitalized, whereas CRP (0.78 ± 0.89 vs. 2.25 ± 2.72 mg/dl) was lower in patients who were not hospitalized. All differences were statistically significant (P < 0.05 for all parameters). When multivariate analysis was performed, serum CRP and reactance values were the only statistically significant predictors of hospitalization (P < 0.05 for both). When a serum CRP concentration of 0.12 mg/dl was considered as a reference range (relative risk 1.0), the relative risk for hospitalization was 7% higher (relative risk = 1.07) for a CRP concentration of 0.92 mg/dl and was 30% (relative risk = 1.30) higher for a CRP concentration of 3.4 mg/dl. When a reactance value of 70 ohms was considered as a reference range with a relative risk of 1.0, the relative risk of hospitalization increased to 1.09 for a reactance value of 43 ohms and further increased to 1.14 for a reactance value of 31 ohms. Conclusions. The results of this study strongly indicate that both nutritional status and inflammatory response are independent predictors of hospitalization in CHD patients. CRP and reactance values by BIA are reliable indicators of hospitalization. Visceral proteins such as serum albumin, prealbumin, and transferrin are influenced by inflammation when predicting hospitalization. When short-term clinical outcomes such as hospitalizations are considered, markers of both inflammation and nutrition should be evaluated. [ABSTRACT FROM AUTHOR]

Measurement of the delivery of dialysis in acute renal failure. Background. Recent studies in patients with acute renal failure (ARF) have shown a relationship between the delivered dose of dialysis and patient survival. However, there is currently no consensus on the appropriate method to measure the dose of dialysis in ARF patients. In this study, the dose of dialysis was measured by blood- and dialysate-based kinetic methods in a group of ARF patients who required intermittent hemodialysis. Methods. Treatments were performed using a Fresenius 2008E volumetric hemodialysis machine with the ability to fractionally collect the spent dialysate. Single-, double-pool, and equilibrated Kt/V were determined from the pre-, immediate post-, and 30-minute post-blood urea nitrogen (BUN) measurements. The solute reduction index was determined from the collected dialysate, as well as the single- and double-pool Kt/V. Results. Forty-six treatments in 28 consecutive patients were analyzed. The mean prescribed Kt/V (1.11 ± 0.32) was significantly greater than the delivered dose estimated by single-pool (0.96 ± 0.33), equilibrated (0.84 ± 0.28), and double-pool (0.84 ± 0.30) Kt/V (compared with prescribed, each P < 0.001). There was no statistical difference between the equilibrated and double-pool Kt/V (P = NS). The solute removal index, as determined from the dialysate, corresponded to a Kt/V of 0.56 ± 0.27 and was significantly lower than the single-pool and double-pool Kt/V (each P < 0.001). Conclusion. Blood-based kinetics used to estimate the dose of dialysis in ARF patients on intermittent hemodialysis provide internally consistent results. However, when compared with dialysate-side kinetics, blood-based kinetics substantially overestimated the amount of solute (urea) removal. [ABSTRACT FROM AUTHOR]

Increased susceptibility to erythrocyte C5b-9 deposition and complement-mediated lysis in chronic renal failure. Background. Decreased red blood cell survival contributes to the anemia of chronic renal failure patients. Because patients on chronic dialysis therapy are frequently exposed to excessive complement activation, we investigated the susceptibility of this patient population to erythrocyte C5b-9 deposition, complement-mediated lysis, and ghost formation. Methods. We developed a flow cytometric assay using antibodies to both glycophorin and the C5b-9 complex to detect C5b-9 deposition on intact erythrocytes and erythrocyte ghosts. Serum C5b-9 levels and C5b-9 deposition on erythrocyte ghosts were measured by enzyme-linked immunosorbent assay. Results. A significant increase in C5b-9 deposition on intact erythrocytes was demonstrated in patients with advanced chronic renal failure (2.2 ± 0.5%) and in patients on chronic maintenance hemodialysis (2.3 ± 0.4%) compared with normal volunteers (0.9 ± 0.1%, P = 0.005 vs. chronic renal failure, P < 0.001 vs. chronic hemodialysis patients). There was also a significantly higher percentage of C5b-9–positive erythrocyte ghosts in patients with advanced chronic renal failure (20.6 ± 5%) and in chronic hemodialysis patients (15.5 ± 3.1%) compared with normal controls (2.6 ± 0.9%, P ≤ 0.001 vs. advanced chronic renal failure and chronic hemodialysis patients). Treatment of erythrocyte preparations with cobra venom factor, which activates the complement cascade, resulted in dramatic increases in the percentages of C5b-9–positive erythrocyte ghosts in patients with chronic renal failure (49.9 ± 6.9%) and in chronic hemodialysis patients (45.0 ± 4.2%) compared with normal volunteers (22.3 ± 2.7%, P < 0.001 vs. chronic renal failure and chronic hemodialysis patients). Erythrocyte membrane expression of the complement regulatory proteins CD59 and CD55 did... [ABSTRACT FROM AUTHOR]

Change in access blood flow over time predicts vascular access thrombosis. Background. Vascular access thrombosis accounts for at least $1 billion dollars in annual expenses and 25% of hospitalizations for chronic hemodialysis patients. Low vascular access blood flow (less than 800 ml/min) has been shown to modestly increase the relative risk for thrombosis in the subsequent three months. In this study, it is hypothesized that a time-dependent decrease in vascular access blood flow may be more predictive of subsequent thrombosis especially in vascular accesses with flows more than 800 ml/min, since it would indicate the development of a critical outlet stenosis in the graft. Methods . Ninety-five accesses in 91 CHD patients were prospectively followed over 18 months. Vascular access blood flow was measured every six months by the ultrasound dilution technique. Thrombotic events were recorded during the three study periods. Results . A total of 34 thrombotic events in 95 accesses were documented through the total study duration. Accesses that thrombosed had a 22% decrease in vascular access blood flow during the first observation period and a further 41% decrease during the second observation period as compared to 4% drop and 15% increase during the first and second observation periods, respectively, for accesses that did not thrombose. There was an estimated 13.6-fold (95%, confidence interval 2.68 to 69.16) increase in the relative risk of thrombosis for accesses with more than 35% decrease in vascular access blood flow compared to those accesses with no change in blood flow. There was no statistical difference in the average vascular access blood flow of all patients over the study period. Conclusions . Accesses that show a large (>15%) decrement in vascular access blood flow are associated with a high risk of thrombosis. Serial measurements of vascular access blood flow predict access thrombosis. [ABSTRACT FROM AUTHOR]

The authors discuss the reasons why they believe that increased research investments are an integral step in helping reduce the public health burden of kidney disease as of 2016, and it mentions how chronic kidney disease (CKD) is a growing public health problem in the U.S. According to the article, more than 20 million Americans have CKD which can lead to end-stage renal disease. U.S. federal expenditures for kidney disease treatment are examined, along with CKD treatment costs.

Background. Our own data shows that 30% of patients in their first 90 days of treatment (tx) vs. 57% of patients greater than 90 days have an albumin of 3.8 g/dL or greater. Stage 5 CKD patients new to hemodialysis (HD) are often malnourished. Oral nutritional supplements (ONS) are often prescribed, but compliance remains a problem. To address compliance and compensate for amino acid losses that occur during HD, Kayser et al. (2002) followed 85 patients for 3 months without ONS, followed by 6 months of in-center ONS. There were significant rises in mean albumin (3.33 ± 0.32 to 3.65 ± 0.26 g/dL), prealbumin, and Subjective Global Assessment scores. To apply these findings to new HD patients, an in-center ONS program was implemented. Program. A team led by the corporate dietitian (RD) developed a policy that addressed implementation of in-center ONS. New HD patients in their first 120 days of tx with albumin of 3.5 or less and/or weight loss greater than 5% in 1 month may receive ONS with each HD treatment until albumin is equal to or greater than 3.8 g/dL, up to 40 doses/year. There are two ONS options per MD order: ProStat RC 30 ml or Nepro 8 oz liquid, each with 15, and 16.7 grams protein, respectively. All doses appear in the electronic medical record med orders to assure dose delivery and ease of tracking, and are delivered to the patient during HD by the nurse, technician, or RD. RDs, who received training via conference calls, trained clinical staff. MDs received information via the MD newsletter. Tracking outcomes. Each dose is documented with data if ONS was refused by the patient, less than 50%, or 50%-100% consumed. A monthly report provides staff with patient-specific ONS data with a count of ONS, consumption data, and albumin levels. Corporate level reports track ONS purchasing data, and clinics prescribing supplements and their volume. Finally, report design is in progress to track changes in albumin level, hospitalization, and mortality, according to amount of ONS consumed vs. patients with no ONS. Conclusion. We believe that this program design is a novel and practical way to apply research findings. The benefits are optimal use of staff time, efficient documentation, and outcomes tracking. New HD patient outcomes will also be improved. [ABSTRACT FROM AUTHOR]

Background: The annualized mortality rate of HD pts in the first 90 days of treatment is up to double the rate of patients past the first 90 days (24%-50%, Ikizler et al., 2007). We previously reported on the RightStart Program for new patients in their first 3 months, which showed improved hospitalization and mortality compared to the control group. The improved mortality was also seen long term at 1 year, which was 9 months after the intervention period was completed (Wingard et al., 2005, see table below). The SPIDER Program is the next phase of RightStart, with increased emphasis on more individualized patient education and empowerment, and innovative ways to improve outcomes, particularly for diabetes mellitus (DM) and nutrition. Approach: This case manager (CM) model provides for a CM to see all eligible new HD patients for a period of 4 months. Initial assessments specific to current HD and DM knowledge, reading level, and diabetes care are carried out. Based on this, an individualized teaching plan is developed to be carried out with the patient by the CM and multidisciplinary team (MDT). In addition, the CM tracks lab values, medical and psychosocial needs to facilitate prompt treatment by working through the MDT. On average, the CM covers 5-7 dialysis clinics, and sees patients in person 8-10 times during the 4 months with phone and family contact as needed. The individualized teaching plan employs strategies to match the patient's learning style and needs. A written patient handbook is provided to each patient and is used as a "textbook." However, other aids such as flip charts, flash cards, reading to patients, audiotapes, and videotapes are used. Implications. This program provides a process to individualize the teaching approach to overcome literacy, visual or language barriers. The CM provides continuity and coordination that prevents fragmentation of care, and staff time is efficiently focused on tasks essential for the MDT to carry out according to their expertise. The specific implementation strategies for SPIDER foot check programs and intradialytic nutritional supplements can be found in separately submitted ANNA abstracts. [ABSTRACT FROM AUTHOR]

Background: ESRD patients with diabetes are clearly at higher risk for foot problems. Studies show that peripheral vascular disease (PVD) and peripheral neuropathy (PN) are much more common in diabetes patients on dialysis than in patients without renal insufficiency. Since PVD and PN contribute to the development of foot problems, diabetes patients on dialysis are at an even-greater risk of developing non-healing foot ulcers leading to amputation and increased morbidity and mortality. To prevent these foot problems, daily foot care and inspection is recommended for all people with diabetes. However, compliance with home foot checks and obtaining therapeutic shoes is often low. Approach: To reduce foot complications, we implemented within the SPIDER program in-center interventions of routine foot checks, patient education and referrals for therapeutic shoes. Case Managers were trained to perform foot exams per a corporate policy/procedure, slide presentation, instructor demonstration and participant return demonstration. The comprehensive foot exam included skin assessment, checking pedal pulses, and sensory testing. Patient handouts were specifically designed for teaching daily foot inspection, lubrication, and safety. Electronic documentation and reporting systems were set up to track foot check completion and actions for follow-up. As a result, on average, 85% or more of foot checks were completed monthly in the dialysis clinics as compared to only sporadic or no foot checks being done. Foot problems were identified promptly and patients were referred to appropriate specialists. Patients that qualified for therapeutic shoes were evaluated and fit when applicable. Implications: The patient/staff awareness and satisfaction in finding foot problems through an efficient and manageable process has been significant. Increasing attention to the diabetic foot can benefit in the areas of prevention, early identification of problems, and prompt referrals that can ultimately prevent amputations and subsequently decrease mortality in this high-risk ESRD population. [ABSTRACT FROM AUTHOR]

We hypothesized that glycosylated hemoglobin (HghA1c) that is averaged for a period of 1 year is relatively stable within hemodialysis (HD) patients and maintains a good correlation with the yearlong averaged random pre-dialysis blood glucose. HD patients in the database of a large dialysis organization with a diagnosis of diabetes and ≥3 HgbA1c results during 2002 who were present from Jan. 1, 2003 to Jan. 1, 2004 formed the study cohort. All available HgbA1c values and pre-dialysis blood glucose measurements were included in computing the averages. There were 18, 867 patients with mean age 63.9 ± 12 years, 52% female, 51% white and 39% black, 90% type 2 diabetes, with mean HgbA1c 6.8 ± 1.5% (median 6.5%) and mean glucose 169 ± 68 mg/dL (median 156 mg/dL). The distribution of the standard deviations (SD) of the HgbA1c in individual patients is shown below. Eighteen percent of patients had HghA1c SD > 1%. The association with random pre-dialysis blood glucose averaged over 1 year is R=0.68 (p < 0.001). The HgbA1c appears stable over the course of the year for most patients with median HgbA1c SD at 0.5%. The prognostic significance of high vs. low HgbA1c variability remains to be determined. [ABSTRACT FROM AUTHOR]

Reports that hemodialysis stimulates muscle and whole body protein loss and alters substrate oxidation. Examination of the potential effects of hemodialysis on energy metabolism; Increase in muscle protein proteolysis due to hemodialysis; Alteration in substrate oxidation during post-hemodialysis with diminished carbohydrate.