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Biomedical subjects

Nathan W Levin

Publications and source records attributed to Nathan W Levin.

At least 37 records · Page 2Linked to original sources

Patients receiving maintenance hemodialysis with low vs high levels of nutritional risk have decreased morbidity.

OBJECTIVE: To compare the demographic and clinical characteristics and outcomes (morbidity) of 442 patients receiving maintenance hemodialysis who are at different levels of nutritional risk. DESIGN: A retrospective, longitudinal, chart review. SETTING/SUBJECTS: An urban, outpatient hemodialysis unit in New York City. Subjects were stratified according to their number of nutritional risk factors: zero to one=low risk, two to three=moderate risk, four to six=high risk. MAIN OUTCOME MEASURES: Mean values for serum albumin <37 g/L, creatinine <884 micromol/L, total cholesterol <4.42 mmol/L, normalized protein nitrogen appearance <0.9 g/kg/day, weight change > -2.5 kg, and body mass index <24. Morbidity indicators were frequency and duration of hospitalizations. STATISTICAL ANALYSES: Descriptive statistics, analysis of variance, and chi 2 analysis were used to summarize data and to analyze mean differences between the groups and differences in categorical variables, respectively. RESULTS: Compared with the high-risk group, the majority of subjects in the low-risk group were younger, male, and did not have diabetes; fewer had two or more comorbidities. The high-risk group had 75% more hospitalizations and spent 195% more days in the hospital than the low-risk group. CONCLUSIONS: Declining values of the nutritional risk factors and higher hospitalization rates were present in the high-risk group. Older subjects, those with diabetes, and those with two or more comorbidities comprised the majority of the high-risk group. More aggressive nutrition counseling and interventions may be needed for high-risk group members to determine if their risk for morbidity could be reduced.

Age Factors↗

Assessment of body composition in long-term hemodialysis patients: rationale and methodology.

Protein-energy malnutrition is seen in patients with advanced stages of chronic kidney disease (CKD) and is even more pronounced in patients receiving long-term hemodialysis treatment. Both entities have great impact on patient morbidity and mortality. Analysis of body composition is an integral part of nutritional assessment and includes the estimation of muscle, fat, and fat-free mass, as well as the extracellular water compartment. Clinical assessment of these compartments is difficult, and gold-standard methods such as tracer dilution, magnetic resonance imaging, and dual-energy x-ray absorptiometry are expensive, cumbersome, and rarely available. We report an ongoing study of body composition in hemodialysis patients involving deuterium and sodium bromide dilution, total body potassium counting, magnetic resonance imaging, whole-body and segmental bioimpedance spectroscopy, and anthropometry. The goals of the study are (1) to validate bioimpedance technology against gold-standard methods for assessment of the various body compartments, (2) to directly quantify visceral adipose tissue mass, a potential source of cytokine production (adipokines) promoting chronic inflammation, and to study its relation to inflammatory markers, and (3) to directly quantify visceral organ mass and to study its relation to uremia toxin generation as assessed by protein catabolic rate and resting energy expenditure. Preliminary results based on up to 40 hemodialysis patients are reported.

Adipose Tissue↗

Estimation of total-body and limb muscle mass in hemodialysis patients by using multifrequency bioimpedance spectroscopy.

BACKGROUND: Skeletal muscle mass can be measured noninvasively with magnetic resonance imaging (MRI), but this is time-consuming and expensive. OBJECTIVE: We evaluated the use of multifrequency bioimpedance spectroscopy (BIS) measurements of intracellular volume (ICV) to model total-body skeletal muscle mass (TBMM) and limb skeletal muscle mass in hemodialysis patients. DESIGN: TBMM was measured by MRI in 20 male and 18 female hemodialysis patients with a median (range) age of 54 y (33-73 y), weight of 78.9 kg (43.2-120 kg), and body mass index (BMI; in kg/m2) of 27.3 (19.4-46.6). We measured total body water (TBW) by using D2O dilution, extracellular volume (ECV) as bromide space, and ICV as TBW minus bromide space. Total body potassium (TBK) measured as 40K was used as an independent model of TBMM. BIS was used to measure whole-body TBW (ankle to wrist) and TBW in the arms and legs. BIS-estimated ICV was used to construct models to calculate limb muscle mass and TBMM. The latter was compared with models derived from isotopic methods. RESULTS: BIS yielded a model for TBMM [TBMM = 9.52 + 0.331 x ICV + 2.77 (male) + 0.180 x weight (kg) - 0.133 x age] (R2 = 0.937, P < 0.0001) as precise as TBK-measured TBMM [TBMM = 1.29 + 0.00453 x TBK (mEq) + 1.46 (male) + 0.144 x weight (kg) - 0.0565 x age] (R2 = 0.930, P < 0.0001) or isotopic methods. BIS models were also developed for measuring leg and arm muscle mass. CONCLUSION: BIS provides an estimate of TBMM that correlates well with isotopic methods in approximating values obtained by MRI and can be used to estimate limb muscle mass.

Adult↗

Bioimpedance, dry weight and blood pressure control: new methods and consequences.

PURPOSE OF REVIEW: Chronic overhydration contributes to the development of left ventricular hypertrophy and a high cardiovascular mortality in end-stage renal disease. Assessment of dry weight is highly dependent on clinical assessment. Bioimpedance technology offers the potential to quantify body fluid compartments and to facilitate dry weight prescription. This review covers recent innovative approaches to dry weight assessment using bioimpedance technology. RECENT FINDINGS: Three different bioimpedance approaches to determine dry weight have been published. The normovolemic/hypervolemic slope method applies whole body multifrequency bioimpedance to assess predialysis total body extracellular fluid volume and compares the extracellular fluid volume/body weight relation at hypervolemia with the standard value in normovolemic individuals. The resistance-reactance graph method uses whole body single frequency bioimpedance for assessment of hydration state and nutritional status from height-adjusted resistance and reactance. The resulting resistance-reactance vector is set in relation to a distribution range in a normovolemic population. An alternative method uses segmental bioimpedance in the form of continuous intradialytic calf bioimpedance to record changes in calf extracellular volume during dialysis. Dry weight by this method is defined as the weight at which calf extracellular volume is not further reduced despite ongoing ultrafiltration. SUMMARY: Although promising, none of these methods has gained much popularity, probably due to the difficulties in understanding bioimpedance and the lack of gold standard methods for dry weight determination. Bioimpedance will improve dry weight assessment, but further refinement of the methods as well as large-scale clinical studies to demonstrate the accuracy and the clinical value of objective dry weight determination are needed.

Blood Pressure↗

Immunomodulating effects of vitamin D analogs in hemodialysis patients.

Apart from its well-known functions in calcium homeostasis and parathyroid hormone regulation, 1,25-(OH)2D3 and its synthetic analogs are being increasingly recognized for their potent antiproliferative, pro-differentiative and immunomodulating activities. The effects of these drugs are exerted either via vitamin D receptor-dependent genomic, or cell-surface receptor-mediated, non-genomic pathways. Several vitamin D analogs with fewer hypercalcemic side effects have been developed for use in secondary hyperparathyroidism. These analogs may potentially improve treatment of autoimmune disorders and graft rejection, and in dialysis patients may open a new opportunity for amelioration of the chronic inflammatory status. It has recently been shown that hemodialysis (HD) patients treated with paricalcitol have lower total and cardiovascular mortality and morbidity rates and experience improved hospitalization outcomes compared with HD patients treated with calcitriol, suggesting a potential beneficial effect in chronic inflammation and the development of cardiovascular disease. Specific studies on the immunomodulating effects of vitamin D are needed in the HD population.

Humans↗

Mechanisms of solute transport in extracorporeal therapies.

Diffusion and convection are the main mechanisms involved in the membrane separation processes occurring in extracorporeal hemodialysis. Operational parameters should be optimized in hollow fiber hemodialyzers to achieve the maximal efficiency. The nature of blood which is a non Newtonian fluid, requires specific attention in the design of dialyzers to ensure that the blood compartment operates properly. Similar attention must be placed in the design of the dialysate compartment to ensure a homogeneous distribution of the fluid and to prevent blood to dialysate flow mismatch. Finally, the membrane represents the third component of the hemodialyzer. Membrane performance depends on the used biomaterial, its biocompatibility, the thickness, the hydrophilic-hydrophobic mixture, the hydraulic permeability and the number and diameter of the pores. In this setting, diffusion and convection tend to reciprocally interfere, producing a final result that depends on the prevalence of one or the other mechanism for every specific solute.

Biological Transport↗

Use of segmental multifrequency bioimpedance spectroscopy in hemodialysis.

Whole body bioimpedance (BI) appears to be accurate and reproducible in the assessment of body composition, but does not appear useful for estimation of dry weight. Segmental BI has been used for the assessment of muscle mass in body segments, such as arms or legs and may be useful for rehabilitation studies. A promising new development is the application of segmental BI for dry weight determination. Changes in extracellular volume of the calf are recorded continuously during HD, thereby allowing the detection of a time-point at which no further volume is removed from the calf despite ongoing ultrafiltration (UF). Continuation of UF beyond this point is associated with an increased risk of intradialytic hypotension. This new technology may help optimizing the prescription of dry weight and UF rates in hemodialysis patients.

Body Composition↗

Interaction between nutrition and inflammation in hemodialysis patients.

The excessive cardiovascular mortality of dialysis patients is at least in part related to chronic inflammation, which is associated with the occurrence of malnutrition. The negative effects of chronic inflammation on nutritional status are mediated by proinflammatory cytokines leading to a reduction in appetite and increased muscle catabolism. However, dietary behavior itself may also independently affect inflammation. Reduced dietary supply of vitamins C, B6, B12 and folate, as well as regular coffee consumption and increased intake of dietary advanced glycation end products may trigger chronic inflammation. On the other hand, a Mediterranean dietary pattern and regular soy intake both have been shown to attenuate chronic inflammation. Dietary interventions aiming to attenuate the chronic inflammatory status in dialysis patients need further exploration.

Diet↗

Modifiable risk factors for cardiovascular disease in CKD patients.

Risk factors for cardiovascular disease (CVD) have been studied extensively in CKD patients. It can be differentiated between modifiable, potentially-modifiable and non-modifiable risk factors. Nonetheless, even for easily modifiable risk factors there is still a lack of data demonstrating the benefit of common interventions, such as statin treatment for dyslipidemia, improvement of HbA1c levels in diabetic patients, implementation of physical exercise, normalization of Hgb and achievement of adequate dry weight in dialysis patients. This article gives an overview of modifiable and potentially modifiable risk factors and available modification strategies.

Cardiovascular Diseases↗

Slow continuous intravenous plasmapheresis (SCIP): clinical applications and hemostability of extracorporeal ultrafiltration.

An intravenous plasmapheresis catheter which excludes >99.4% of platelets from external ultrafiltration circuits is currently undergoing safety and efficacy trials for fluid removal from NYHA class II-IV congestive heart failure patients resistant to diuretic drug therapy. In animals, the SCIP catheter allowed a four fold increase in ultrafiltration efficiency without hemolysis, hemoinstability or external cartridge changes in 72 hours of treatment. Further, systemic anticoagulation was not required. These techniques might be envisioned for treatment of fluid overload in heart failure, surgery or trauma and may have applications in therapeutic apheresis, venous thrombosis, liver disease or autologous tissue engineering.

Animals↗

Factors for increased morbidity and mortality in uremia: hyperphosphatemia.

Hyperphosphatemia is a metabolic abnormality present in the majority of patients treated by dialysis. Inorganic phosphorus (iP) can be categorized as a true uremic toxin given its known in vivo and in vitro effects and the ability to reduce these effects by normalizing iP levels. However, despite regular and adequate dialysis treatment, the goal of normalization of phosphorus levels rarely is achieved. This article briefly evaluates the significance of hyperphosphatemia in hemodialysis patients, current therapeutic approaches, and describes a new model for evaluating the dialysis prescription for iP balance.

Humans↗

Mortality among hemodialysis patients in Europe, Japan, and the United States: case-mix effects.

BACKGROUND: The Dialysis Outcomes and Practice Patterns Study is well suited to identify case-mix effects, given its extensive data set. The data set was used to examine the influence of case-mix variables on mortality and the extent to which these variables account for differences in mortality across regions, as well as the prevalence and incidence of hepatitis B and hepatitis C. METHODS: Demographic and comorbid disease features were determined for 8,615 patients internationally; mortality was recorded for this cohort, plus replacement patients (total n = 16,720), from 1996 to 2002. Mortality was associated with increasing age, nonblack race, coronary artery disease, congestive heart failure, other cardiac disease, diabetes mellitus, peripheral vascular disease, cerebrovascular disease, absence of hypertension, lung disease, cancer, human immunodeficiency virus infection, gastrointestinal bleeding, neurologic disease, psychiatric disease, cellulitis/gangrene, hepatitis C, and smoking. RESULTS: US patients were slightly older than those in Europe or Japan and had the highest prevalence of diabetes, coronary artery disease, congestive heart failure, peripheral vascular disease, and cerebrovascular disease. CONCLUSION: Upon adjusting for case-mix to assess mortality across facilities, it was found that regional differences in mortality (highest in the United States and lowest in Japan) and differences across facilities within nations remain after such corrections. It is likely that practice patterns account for some of this variation. Prevalence of hepatitis B virus (HBV) across facilities increased as the number of dialyzing patients per facility increased; risk of HBV seroconversion decreased among facilities using protocols for treatment of patients with HBV infection. Greater employment of staff with at least 2 years of formal nursing training was associated with lower prevalence of hepatitis C virus infection and lower seroconversion risk.

Comorbidity↗

Frequency of patient-physician contact and patient outcomes in hemodialysis care.

There is little evidence supporting the widespread belief that regular patient-physician contact in chronic disease management leads to better patient outcomes. The objective of this study was to examine the relationship of the frequency of patient-physician contact with several patient outcomes in a prospective cohort study begun in 1995 of incident hemodialysis patients treated at 75 US dialysis clinics. Average frequency of patient-physician contact at each clinic was determined by clinic survey (low, monthly or less frequent; intermediate, between monthly and weekly; high, more than weekly). The authors used logistic, Poisson, and Cox proportional hazards regression analyses to assess the relationship between contact and satisfaction, quality of life, patient adherence, hospitalizations, and mortality. Of 735 hemodialysis patients, 14.3% were treated at clinics with high frequency of contact, 65.2% intermediate, and 20.5% low. Patients treated at clinics reporting less frequent physician contact had lower odds of rating the frequency at which they saw a nephrologist excellent (low: adjusted OR = 0.39, 95% CI, 0.23-0.67; intermediate: adjusted OR = 0.57, 95% CI, 0.37-0.87; reference, high) and greater odds of nonadherence (low: adjusted OR = 2.89, 95% CI, 1.01-8.29; intermediate: adjusted OR = 1.58, 95% CI, 0.78-3.19). However, patient survival did not vary by frequency of physician contact (low: adjusted RH = 0.87, 95% CI, 0.53-1.44; intermediate: adjusted RH = 1.33, 95% CI, 0.82-2.13), nor did patients' overall ratings of care, hospitalization rates, or quality of life measures. Although less frequent patient-physician contact was associated with lower patient satisfaction with that contact and patient nonadherence, it was not associated with several other outcomes of care. Future studies are needed to assess the individual frequency and nature of physician contact over time, including total time spent with the patient and quality of the interaction, to guide the provision of patient-centered and cost-effective care.

Cohort Studies↗

Inflammation and reduced albumin synthesis associated with stable decline in serum albumin in hemodialysis patients.

BACKGROUND: The concentration of albumin in serum is maintained by its rates of synthesis, catabolism, and distribution between vascular and extravascular compartments. Albumin synthesis is suppressed when there is inflammation or inadequate protein intake. This study was conducted to establish whether a decline in serum albumin of >0.3 g/dL was accompanied by a change in albumin synthesis and if so whether these changes were associated with increased levels of acute phase proteins and/or with a decrease in equilibrated normalized protein catabolic rate (enPCR). METHODS: Seventy-nine patients in the National Institutes of Health (NIH)-sponsored HEMO Study had baseline measurements of albumin synthesis (measured kinetically as the disappearance of [125]I human serum albumin), the serum concentrations of albumin, transferrin, C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1AG), ceruloplasmin, interleukin-6 (IL-6), plus monthly measurements of enPCR. The plasma levels of all proteins and enPCR were measured regularly over 2 years or until serum albumin decreased by >0.3 g/dL on two sequential measurements. Albumin synthesis was measured a second time when serum albumin declined by >0.3 g/dL or after 2 years. RESULTS: Fifty-nine patients [21 with a significant decrease in serum albumin (decliners) and 38 with stable values of serum albumin] had albumin synthesis measured twice. A decline in albumin concentration and synthesis was associated with an increase in alpha1AG when data from all patients were analyzed as a group. In decliners, albumin synthesis decreased significantly but was unchanged in stable. Likewise, in decliners, IL-6, CRP, alpha1AG, and ceruloplasmin increased significantly but were unchanged in stable. enPCR was unchanged in both groups and was not associated with either changes in albumin level or synthesis in the whole group. CONCLUSION: A decrease in serum albumin of >0.3 g/dL that persists for a period of 6 weeks is associated a decrease in albumin synthesis. This response is associated with evidence of activation of the acute phase response (inflammation) but not with changes in enPCR. In well-dialyzed patients, inflammation is the principal cause of a decrease in serum albumin while protein intake plays an insignificant role.

Acute-Phase Reaction↗

Mechanisms determining the ratio of conductivity clearance to urea clearance.

BACKGROUND: Effective conductivity clearance (K(ecn)) has been reported to be a surrogate for effective urea clearance (K(eu)), where both are usually defined respectively as the dialyzer conductivity and urea clearances (K(cn), K(u)) corrected for access recirculation (R(ac)). However, many investigators have reported K(ecn)/K(eu) to be <1 and postulated anatomic distribution of Na in plasma water, cardiopulmonary recirculation (R(cp)), and high rates of urea clearance (K(u)) as causes. The aims of these studies were to devise analytic models of these mechanisms and to clinically evaluate the modeled relationships. METHODS: We modeled and measured: (1) Na osmotic distribution volume flow rate (Q(osmNa)) in dialyzer blood flow; (2) the separate and combined effects of R(ac) and R(cp) on K(u) and K(cn); and (3) a novel mechanism reducing the conductivity diffusion gradient during measurement of K(cn) by recirculation through the dialyzer (R(s)) of a change in systemic blood conductivity (Delta Cn(s)) induced by the abrupt changes in dialysate inlet Na (Delta C(diNa)) required for the measurement of K(cn). RESULTS: The ratio Q(osmNa)/Q(bi)= 1.00 +.03, N= 19 (Q(bi)= total blood water flow rate). Modeling showed that the effects of R(ac), R(cp), and R(s) on K(cn) can be quantified as K(ecn)= K(cn)(1 -Delta Cn(bi)/Delta Cn(di)), where Delta C(nbi) is any change in conductivity in the dialyzer blood inlet stream during a measurement, and the effect of a combination of these mechanisms is the product of the effects of individual mechanisms. A single-step dialysate profile (with R(ac)= 0) resulted in measured Delta C(biNa)/Delta C(diNa)= 2.5/15, K(ecn)/K(eu)= 0.83, N= 21 because of R(s) and R(cp), but with a two-step, high/low profile (P(h/L)) we found these respective values to be -0.6/20 and 0.97, N= 19. The ratio K(ecn)/K(eu3)= 1.06 +.02, M + SE, N= 35 (K(eu3)= Ku corrected to reflect both access and cardiopulmonary recirculation). The ratio K(ecn)/K(eu1) (K(eu1) is K(u) corrected to reflect access recirculation only) = 1.01 +.07, N= 297, with no bias on Bland Altman analysis. CONCLUSION: We conclude that (1) the osmotic Na distribution volume in blood is total blood water; (2) K(ecn) measured with a short, high/low, and asymmetric dialysate profile shows R(ac) effect but neither R(cp) nor R(s) effects on K(ecn) and K(ecn)/K(eu)= 1.0; (3) the K(ecn)/K(eu) ratio is strongly dependent on the type of dialysate profile used, which must be optimized to minimize net Na transfer to and from blood during measurement of conductivity clearance to avoid erroneous underestimation of K(ecn) and K(ecn)/K(eu) ratios <1.

Coronary Circulation↗

Monocyte apoptosis in uremia is normalized with continuous blood purification modalities.

Uremia is associated with a state of immune dysfunction. Dysregulation of homeostasis may be directly related to abnormal apoptosis regulation in uremia, which is crucial for the maintenance of the biological system. We demonstrated that plasma from three groups of uremic subjects, i.e. hemodialysis (HD) patients, peritoneal dialysis (PD) patients and patients with predialysis chronic renal failure (CRF), has different apoptotic potential on U937 monocytes. The plasma of HD and CRF subjects when incubated with U937 cells induced higher levels of apoptosis compared with that of PD and control subjects (HD 26.08 +/- 11.39, CRF 24.87 +/- 9.07, PD 12.13 +/- 4.51, controls 11.69 +/- 4.02). Furthermore, the phagocytic ability of U937 cells incubated with the various plasma demonstrated an impaired response in the HD and CRF subjects (HD 27.56 +/- 6.67, CRF 30.24 +/- 9.08, PD 36.55 +/- 9.80, controls 40.04 +/- 6.98). These results suggest that continuous blood purification, such as in PD, may have advantages over intermittent therapies in removing uremic apoptotic molecules and potentially maintaining biological function and homeostasis.

Apoptosis↗