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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.

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]

Use of intradialytic oral nutritional supplements (ONS) improve nutritional biomarkers but an association with hospitalization risk is unexplored. We evaluated hospitalization events from all causes (HOS), comparing patients with serum albumin ≤3.5 g/dL who received monitored ONS (at no patient cost) during chronic outpatient hemodialysis (HD) as part of a standardized national program in Fresenius Medical Care, North America facilities, with eligible patients who did not receive ONS (controls). Study enrolment covered Q4‐2009 and follow‐up was until 12/31/10. Patients who received ONS outside of the program or started during 2010 were excluded. Two protein bars and two liquid formulations of ONS options were offered – – which were available until albumin was ≥ 4.0 g/dL. Overall, HOS was lower in the ONS group (N= 7,264) at 2.5 vs. 2.7 episodes/pt‐year for controls (N= 13,853), p<0.001. The unadjusted time to 1st HOS hazard ratio for ONS was 0.92 (0.88, 0.95) and after adjustment for baseline case‐mix, HOS 30‐days prior to study entry, and 5 HD quality indicators was 0.93 (0.90, 0.96). Although limited by the observational design, these results indicate lower HOS associated with ONS use in malnourished chronic HD patients with albumin ≤3.5 g/dL. [ABSTRACT FROM AUTHOR]

Use of intradialytic oral nutritional supplements (ONS) improve nutritional biomarkers but an association with survival has not been proven. We evaluated mortality, comparing patients with serum albumin ≤3.5 g/dL who received monitored ONS (at no patient cost) during chronic outpatient hemodialysis (HD) as part of a standardized national program in Fresenius Medical Care, North America facilities, with eligible patients who did not receive ONS (controls). Participation was promoted but not mandatory. Study enrolment covered Q4‐2009 and follow‐up was until 12/31/10. Patients who received ONS outside of the program or started during 2010 were excluded. Two protein bars and two liquid formulations of ONS options were offered, which were available until albumin was ≥ 4.0 g/dL. Crude mortality in the ONS group (N= 7,264) was 29.4% vs. 36.6% for controls (N= 13,853), p<0.001. Compared to controls, the unadjusted mortality hazard ratio for ONS was 0.70 (0.67, 0.74) and after adjustment for baseline case‐mix and 5 quality indicators was 0.68 (0.64, 0.71). Although limited by the observational design, these results indicate favorable survival associated with ONS use in malnourished chronic HD patients with albumin ≤3.5 g/dL. [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.

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]

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]

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.

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]