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Nathan W Levin

Publications and source records attributed to Nathan W Levin.

At least 55 records · Page 3Linked to original sources
PubMed2004

Sorbents in acute renal failure and end-stage renal disease: middle molecule and cytokine removal.

Renal replacement therapy in acute renal failure (ARF) and chronic renal failure (end-stage renal disease; ESRD) has been based on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle-molecular-weight toxins, consisting of low-molecular-weight proteins and peptides (LMWP) and cytokines involved in inflammation. High-flux dialyzers are not efficient at removing LMWP, and for this reason, sorbents have been studied to augment or replace dialysis. Removal of LMWP such as beta2-microglobulin, leptin, complement factor D, angiogenin and cytokines such as interleukin (IL)-1, IL-6, IL-10, IL-18 and tumor necrosis factor-alpha has been established in animal models of sepsis and in ESRD patients using sorbents. Sorbent devices added to hemodialysis, or the use of such devices alone in inflammatory states, including sepsis, ARF, cardiopulmonary bypass, pre-explantation of donor organs and ESRD, are being studied.

Acute Kidney Injury↗
PubMed2004

Non-specialist ultrasound measuring of access flow: new technology.

A new ultrasound instrument has been developed, using vector Doppler and embedded machine intelligence, to enable measurement of access flow rates by non-specialists. Ultrasound measurement of access flow can be performed with the patient off the dialysis machine, avoiding the hemodynamic changes that may affect indicator-dilution methods. A research version of the instrument was tested on flow phantoms simulating graft flow, and showed accuracy better than 5%. A non-specialist measured flow in the access grafts of 7 consenting dialysis patients; the instrument showed flows commensurate with indicator-dilution-measured flows, but with less variability. Measurements were made in less than 5 min per patient. The cost per measurement is calculated to be significantly less than that of present methods of measuring flow. The new instrument may become a useful tool for monitoring flow in accesses to extend their life.

Allied Health Personnel↗
PubMed2004

Extracorporeal therapies in non-renal disease: treatment of sepsis and the peak concentration hypothesis.

In the setting of intensive care, patients with acute renal failure often present a clinical picture of the systemic inflammatory response syndrome (SIRS). SIRS can be caused by bacterial stimuli or by non-microbiological stimuli that induce a significant inflammatory response. When this response is exaggerated, the patient experiences multiple organ system failure and a condition of sepsis also defined as a systemic malignant inflammation. This is mostly characterized by an invasion of cytokines and other pro-inflammatory mediators into the systemic circulation where major biological effects take place, including vasopermeabilization, hypotension and shock. At the same time, the monocyte of the septic patient seems to be hyporesponsive to inflammatory stimuli to a certain extent. In this condition, the patient faces a situation of hyperinflammation but at the same time of immunodepression expressing a clinical entity defined as counter anti-inflammatory response syndrome. The general picture of the clinical disorder is therefore better characterized by an immunodysregulation than by a simple pro- or anti-inflammatory disorder. Due to the short half-life of cytokines and other mediators spilled over into the circulation, it is extremely difficult to approach the problem at the right moment with the right pharmacological agent. For these reasons, the peak concentration hypothesis suggests that continuous renal replacement therapies, due to their continuity and unspecific capacity of removal, might be beneficial in cutting the peaks of the concentrations of both pro- and anti-inflammatory mediators, restoring a situation of immunohomeostasis. Thus the patient may benefit from a lesser degree of immunodysregulation and he/she may restore a close-to-normal capacity of response to exogenous stimuli.

Animals↗
PubMed2003

Breath ethane in dialysis patients and control subjects.

Oxidant stress may play a role in the accelerated pathology of patients on dialysis, especially in the development of cardiovascular disease, which is a frequent condition in end-stage renal disease (ESRD) patients. Measurement of hydrocarbons can be employed to assess oxidant stress since breath hydrocarbons have been directly traced to in vivo breakdown of lipid hydroperoxides. We undertook to measure ethane, a major breath hydrocarbon, in 15 control subjects, 13 patients on peritoneal dialysis (PD), and 35 patients on hemodialysis (HD). Within the HD group, we separately examined 12 diabetic and 23 nondiabetic patients. Breath samples were collected after patients had breathed purified air for 4 min, and ethane content was measured by GC and expressed as pmoles/kg-body weight-minute (pmol/kg-min). As the data for the hemodialysis patients appeared skewed, nonparametric statistical techniques were employed to analyze these data, which are reported as median and interquartile range (IQR). Ethane levels were similar in 15 control subjects (median, 2.50 pmol [1.38-3.30]/kg-min] and 13 PD patients (median, 2.51 pmol [1.57-3.17]/kg-min). Breath ethane was significantly elevated in a portion (18 of 35 patients, 52%) of the HD patients (median, 6.16 pmol [4.46-8.88]/kg-min) (p <.001 vs. control, Mann-Whitney U test). Two of the diabetic HD patients showed extremely high values of breath ethane. Breath ethane was not altered by a single hemodialysis session, suggesting that long-term metabolic processes contribute to its elevation. Measurement of breath ethane may provide insight into severity of oxidant stress and metabolic disturbances, and provide guidance for optimal therapy and prevention of pathology in patients on long-term hemodialysis.

Adult↗
PubMed2003

Measurement of intraperitoneal volume by segmental bioimpedance analysis during peritoneal dialysis.

BACKGROUND: Currently, ultrafiltration during peritoneal dialysis is determined from direct measurement of weight differences between the initial filling and final draining volumes. A new technique based on segmental bioimpedance analysis (SBIA) has been developed to accurately measure intraperitoneal volume continuously during peritoneal dialysis. METHODS: Twenty-two peritoneal dialysis patients were studied in a supine position during peritoneal dialysis consisting of 4 tidal exchanges (TPD). For bioimpedance measurements, 4 electrodes were placed, 1 on each hand and foot, to inject an alternating current. Sensing electrodes were placed on the lower ribs and the buttocks on both sides of the body. Calibration of the SBIA method was performed by first filling a known volume of dialysate to establish the relationship between change in resistance and a known fluid volume in the peritoneal cavity. The increase of fluid volume in the peritoneal cavity during dwell time was considered to be equal to net ultrafiltration volume occurring during this period. These measurements were compared with those obtained by the difference in weight between the total filling and draining volumes. RESULTS: The change in intraperitoneal volumes measured by differences in weight (0.39 +/- 0.29 L) did not differ significantly from those established from SBIA (0.41 +/- 0.31 L). Bland-Altman analysis yielded limits of agreement of 0.12 L. CONCLUSION: The SBIA technique provides a continuous noninvasive approach to the measurement of changes in intraperitoneal fluid volume.

Adult↗
PubMed2003

Impact of albumin synthesis rate and the acute phase response in the dual regulation of fibrinogen levels in hemodialysis patients.

BACKGROUND: Fibrinogen is a risk factor for cardiovascular disease. It also is an acute phase protein (APP) and its plasma concentration increases with inflammation. Fibrinogen synthesis correlates with albumin synthesis in nephrotic patients and in patients with an expanded plasma volume even when serum albumin is normal and there is no inflammatory disease. The relationships among albumin synthesis, the acute phase response and plasma fibrinogen levels in hemodialysis patients are unknown. METHODS: In 74 hemodialysis patients, albumin synthesis, plasma volume (PV) and acute phase proteins (APPs) C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1 AG), ceruloplasmin (Cer), and interleukin 6 (IL-6) were measured in serum and fibrinogen in plasma, and the results analyzed by multiple regression analysis. CRP, IL-6, alpha1 AG, Cer and fibrinogen were measured monthly, which enabled us to determine whether changes in these APPs correlated with the levels of and variability in plasma fibrinogen over time using a longitudinal modeling approach. Length of follow-up for the 74 patients ranged from 3.25 to 67.5 months. RESULTS: Baseline fibrinogen (548.6 +/- 106. 4 mg/dL) was significantly greater than levels reported for normal adults and correlated positively with albumin synthesis (P < 0.001), age (P < 0.001) and log CRP (P = 0.002) and negatively with PV (P < 0.001). Longitudinally, fibrinogen varied positively with long-lived APPs, Cer and alpha1 AG, as well as the short-lived APP, CRP. CONCLUSION: Plasma fibrinogen concentration is high in HD patients and directly correlates with increased albumin synthesis rates and the serum levels of APPs. Fibrinogen levels also correlate negatively with PV. Fibrinogen levels vary over time in synchrony with levels of other long-lived APPs, supporting the hypothesis that fibrinogen is regulated in part as a component of the acute phase response and in part by factors that increase albumin synthesis.

Acute-Phase Reaction↗
PubMed2003

Erythropoeitin dose variation in different facilities in different countries and its relationship to drug resistance.

BACKGROUND: The correction of anemia using erythropoeitin (EPO) is accorded high priority in the management of patients undergoing hemodialysis (HD). Target hemoglobin (Hb) levels have been established in many countries. Following an observation that the mean facility EPO dose in a chain of facilities in the United States varied by more than two-fold, an examination of the practice of anemia correction in other settings was carried out. METHODS: We reviewed demographic and laboratory parameters in prevalent HD patients in 50 United States facilities and in a single HD facility in Vicenza, Italy. The mean EPO dose profile of the United States facilities was compared with the profiles in 10 facilities in the eastern United Kingdom (UKER) and in 20 facilities reporting to the United Kingdom Renal Registry (UKRR). Analysis of the factors that correlate with EPO resistance was carried out using the United States and Italian data. RESULTS: The average EPO doses, by facility, in the 51 United States, the 10 UKER, and the 19 UKRR facilities were 19,569, 8,416, and 7,992 international units per week (IU/wk), respectively. While examination of the UKRR revealed a similar degree of inter-facility variation (2.6-fold), much larger doses of EPO were being administered in the United States patients, particularly in the low Hb group. Multivariate analysis of the United States data suggested that factors related to inflammation, including low albumin, the use of tunneled catheters for vascular access, and low protein catabolic rate (enPCR) correlated with low Hb and relative EPO resistance. CONCLUSION: Despite similar guidelines for anemia management, significant differences in practice are observed. While there seems to be a reluctance to administer large EPO doses to individual patients in Europe, this does not seem to apply in the United States, where more EPO is given. EPO resistance seems relative rather than absolute in many patients, allowing some to respond to the higher doses.

Aged↗
PubMed2003

Longitudinal and cross-sectional effects of C-reactive protein, equilibrated normalized protein catabolic rate, and serum bicarbonate on creatinine and albumin levels in dialysis patients.

BACKGROUND: Loss of muscle mass and hypoalbuminemia each may result in part from either malnutrition, inflammation, or a combination of both. Short-term acidosis increases muscle protein catabolism and inhibits albumin synthesis. METHODS: We analyzed albumin and creatinine levels as outcome variables and their association with C-reactive protein (CRP) level, equilibrated normalized protein catabolic rate (enPCR), and serum bicarbonate level as independent variables from laboratory data obtained from patients in the Hemodialysis Study. Analyses controlled for race, sex, age, body mass index, and randomized treatment group. RESULTS: Albumin level correlated with both enPCR and CRP level, but not serum bicarbonate level, in both cross-sectional and longitudinal analyses. Effects of CRP level and enPCR were not linear. Albumin level correlated positively with enPCR for an enPCR less than 1.0 g/kg/d, but not for a greater enPCR, and correlated inversely with CRP level for a CRP level greater than 13 mg/L. Similarly, creatinine level correlated with both enPCR and CRP level. As in the case of albumin level, effects were not linear. Creatinine level correlated positively with enPCR for values less than 1.0 g/kg/d, but not for greater enPCR values. In contrast to albumin level, creatinine level correlated negatively with serum bicarbonate level, even when adjusted for enPCR. CONCLUSION: Albumin and creatinine levels are independently associated with nutrition (enPCR) and inflammation (CRP level). The cross-sectional relationship with enPCR is apparent only at values less than 1.0 g/kg/d. CRP level is associated with reduced albumin and creatinine values when increased to values greater than 5.6 mg/dL. CRP may be increased to levels associated with increased cardiovascular risk with little or no effect on either serum albumin or creatinine level. Thus, a normal albumin level does not exclude elevated CRP levels.

Acidosis↗
PubMed2003

Beta-2 microglobulin in ESRD: an in-depth review.

Beta-2 microglobulin is the most widely studied low-molecular-weight protein in end-stage renal disease. It is known to cause dialysis-related amyloidosis (DRA), by virtue of its retention when renal function fails, its deposition in tissues, its aggregation into fibrils, and its ability to become glycosylated. The onset of DRA may be protracted by the use of noncellulosic membranes, especially when high-volume hemodiafiltration is used in the treatment of renal failure. Adsorptive methods have been developed to improve the removal of beta-2 microglobulin. There seems to be a relative risk reduction in mortality when patients are treated with dialysis membranes that have a higher clearance of beta-2 microglobulin.

Amyloidosis↗
PubMed2003

Effects of high-flux hemodialysis on clinical outcomes: results of the HEMO study.

Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P = 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with <3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation.

Female↗
PubMed2003

Methods and reproducibility of measurement of resistivity in the calf using regional bioimpedance analysis.

UNLABELLED: The usefulness of regional bioimpedance analysis (RBIA) in determining the dry weight in dialysis patients is currently being investigated. The aim of this study was to evaluate the reproducibility of measurement of resistivity in the calf. METHODS: Twenty-five normal subjects and 10 patients undergoing regular hemodialysis were studied. Four electrodes inserted into a blood pressure cuff were placed on the calf. Bioimpedance was continuously measured over 3- to 5-min periods (Xitron Hydra). After a resting period of 1 min, cuff pressure was increased to above the systolic blood pressure (SBP) for a few seconds to expel excess ECF fluid and then deflated. The effect on recordings of moving the electrodes 2 cm higher and then 2 cm lower than the normal position was studied in 8 normal subjects. In a second study of reproducibility, post-dialysis measurements were made twice in 10 patients who maintained the same post-dialysis target weight throughout the study period. RESULTS: The mean resting resistivity rho(0) in normal subjects was 532.6 +/- 95 omega.cm rising to 583.9 +/- 99.7 omega.cm when cuff pressure was applied rho(p). The average values of rho(0) and rho(p) in patients post-dialysis were 489 +/- 74 and 537 +/- 77 respectively showing that there were no significant differences in rho(0) and rho(p) between normal subjects and patients post-dialysis. The mean values of change in resistivity when the electrodes were shifted between the lowest and highest positions on the calf were -3.66 +/- 4.45 and -1.44 +/- 3.82%, respectively. Repeat measurement of resistivity in patients post-dialysis varied by 2.04 +/- 2.29% while post-dialysis body weight varied by 0.17 +/- 0.47%. CONCLUSION: In this study, resistivity measurement by RBIA at the calf showed similar levels of fluid loading in patients post-dialysis as in normal subjects. This study also showed that change in electrode position resulted in a mean change in resistivity of <5% and repeated measurements showed a change in resistivity <3% while body weight changes were <0.2%. This technique appears to have an acceptable level of reproducibility for its application to the assessment of patient hydration.

Adult↗
PubMed2003

Sorbents in acute renal failure and the systemic inflammatory response syndrome.

Renal replacement therapy in acute renal failure is currently focused on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle molecular weight toxins, consisting of small proteins, and cytokines involved in the systemic inflammatory response syndrome (SIRS). Conventional high-flux dialyzers are not efficient at removing these molecules, prompting the investigation of sorbents to augment or replace dialysis. Sorbents have been developed to modulate SIRS by targeting cytokines such as IL-1, IL-6, IL-10, IL-18 and TNF, among others. Extensive pre-clinical studies are underway to demonstrate the clinical utility and safety of either adding sorbent hemoadsorption devices to hemodialysis, or the use of such devices alone in SIRS, sepsis, acute renal failure, cardiopulmonary bypass and end-stage renal disease.

Acute Kidney Injury↗
PubMed2003

Slow continuous intracorporeal plasmapheresis for acute fluid overload.

Intermittent dialysis is still the predominant treatment for acute or chronic renal insufficiency in the USA despite increasing evidence that slower and longer fluid management therapies are more beneficial to the patient. We have investigated the use of slow continuous intracorporeal plasmapheresis (SCIP) as a more efficient and hemodynamically stable alternative means of treating acute fluid overload. In this paper we discuss preliminary observations on the safety of SCIP catheter insertion, fluid removal, extraction and pathology in Yorkshire pigs. SCIP catheters removed plasma for extracorporeal plasma water removal without significant gross or histopathological changes. Blood chemistry and cell counts remained stable during therapy. Toxicological studies indicated no pyrogenicity, hemolysis, cytotoxicity, acute systemic toxicity, delayed-type hypersensitivity, or blood recalcification coagulation inhibition. Intracutaneous extracts caused only mild irritation. SCIP therapy appears to be safe for use in the removal of plasma and plasma water from experimental animals.

Acute Disease↗
PubMed2003

A kinetic model of inorganic phosphorus mass balance in hemodialysis therapy.

BACKGROUND: There is growing evidence that inorganic phosphorus (iP) accumulation in tissues (dTiP/dt) is a risk factor for cardiac death in hemodialysis therapy (HD). The factors controlling iP mass balance in HD are dietary intake (GiP), removal by binders (JbiP) and removal by dialysis (JdiP). If iP accumulation is to be minimized, it will be necessary to regularly monitor and optimize GiP, JbiP and JdiP in individual patients. We have developed a kinetic model (iPKM) designed to monitor these three parameters of iP mass balance in individual patients and report here preliminary evaluation of the model in 23 HD patients. METHODS: GiP was calculated from PCR measured with urea kinetics; JdiP was calculated from the product of dialyzer plasma water clearance (K(pwiP)) and time average plasma iP concentration (TACiP) and treatment time (t); a new iP concentration parameter (nTAC(iP), the TACiP normalized to predialysis CoiP) was devised and shown to be a highly predictable function of the form nTAC(iP) = 1 - alpha(1 - exp[-betaK(pwiP). t/ViP]), where the coefficients alpha and beta are calculated for each patient from 2 measure values for nTAC(iP), K(pwiP).t/ViP early and late in dialysis; we measured 8-10 serial values for nTAC(iP), K(pwiP). t/ViP over a single dialysis in 23 patients; the expression derived for iP mass balance is DeltaTiP = 12(PCR) - [K(pwiP)(t) (N/7)][CoiP(1 - alpha(1 - exp[-beta(Kt/ViP)]))] - k(b).Nb. RESULTS: Calculated nTAC(iP) = 1.01(measured nTAC(iP)), r = 0.98, n = 213; calculated JdiP = 0.66(measured total dialysate iP) + 358, n = 23, r = 0.88, p < 0.001. Evaluation of 10 daily HD patients (DD) and 13 3 times weekly patients with the model predicted the number of binders required very well and showed that the much higher binder requirement observed in these DD patients was due to much higher NPCR (1.3 vs. 0.96). CONCLUSION: These results are very encouraging that it may be possible to monitor the individual effects of diet, dialysis and binders in HD and thus optimize these parameters of iP mass balance and reduce phosphate accumulation in tissues.

Death↗
PubMed2003

Daily dialysis: the long and the short of it.

There is considerable enthusiasm for daily hemodialysis despite the increased time commitment required of patients because of reported improvements in patient well-being, appetite and blood pressure control. To date, this therapy has been largely empirical and has been defined primarily by treatment time (t) and categorized as short daily hemodialysis (SDHD) with t about 2 h and long nocturnal hemodialysis (LNHD) with t 8-9 h. It is the authors' view that studies comparing clinical outcome with SDHD and LNHD to conventional hemodialysis (CHD) must have dialysis dosage well defined if they are to provide generalizable results. There is a broad range and overlap in the magnitude of solute removal in reported studies of SDHD, LNHD and CHD, which is illustrated here through kinetic consideration of four solutes: (1) urea; (2) inorganic phosphorus (iP); (3) beta(2)-microglobulin (beta(2)M) and (4) Na/water. The following observations can be made: (1) Patient subjective reports of increased appetite and protein intake may correlate poorly with kinetic calculation of protein catabolic rate. (2) A model of iP mass balance was developed and indicates that iP removal with CHD is inadequate; current SDHD is also inadequate to highly excessive depending on the dose of dialysis. (3) beta(2)M removal with SDHD is virtually the same as reported for LNHD, reflecting major differences in dialyzer membranes used. (4) The decrease in predialysis overhydration is a predictable function of the number of dialyses per week and may be one of the most important benefits of more frequent dialysis. (5) The standard K(t)/V (stdK(t)/V) provides a uniform method of dose calculation but the therapy prescription should also include consideration of the other solutes evaluated above.

Day Care, Medical↗
PubMed2002

Effect of dialysis dose and membrane flux in maintenance hemodialysis.

BACKGROUND: The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain. METHODS: We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer. RESULTS: In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.3+/-2.5 percent, the single-pool Kt/V was 1.32+/-0.09, and the equilibrated Kt/V was 1.16+/-0.08; in the high-dose group, the values were 75.2+/-2.5 percent, 1.71+/-0.11, and 1.53+/-0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as compared with the standard-dose group was 0.96 (95 percent confidence interval, 0.84 to 1.10; P=0.53), and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 (95 percent confidence interval, 0.81 to 1.05; P=0.23). The main secondary outcomes (first hospitalization for cardiac causes or death from any cause, first hospitalization for infection or death from any cause, first 15 percent decrease in the serum albumin level or death from any cause, and all hospitalizations not related to vascular access) also did not differ significantly between either the dose groups or the flux groups. Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients. CONCLUSIONS: Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.

Adult↗