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Biomedical subjects

N W Levin

Publications and source records attributed to N W Levin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Elevated plasma F2-isoprostanes in patients on long-term hemodialysis.

BACKGROUND: End-stage renal disease (ESRD) patients on long-term hemodialysis (HD) may be under increased oxidative stress, caused by either HD or renal failure. Plasma F2-isoprostanes have been established as an important indicator of in vivo oxidative stress. METHODS: Plasma esterified F2-isoprostanes were measured in 25 HD patients and 23 controls with normal renal function, employing gas chromatography-mass spectrometry with negative chemical ionization (GC-MS-NCI). C-reactive protein (CRP) was determined concurrently in patients and controls by enzyme-linked immunosorbent assay (ELISA). alpha-Tocopherol, retinol, albumin and creatinine were also determined. RESULTS: The average total esterified F2-isoprostanes in the ESRD patients was 1.62 +/- 0.73 vs. 0.27 +/- 0.10 ng/mL in controls (P < 0.001), with no overlap between patients and controls. Plasma F2-isoprostanes in diabetic ESRD patients were similar to F2-isoprostanes in patients with other causes for renal failure. In a subset of 10 of these ESRD patients evaluated eight months after the initial measurement, plasma-esterified F2-isoprostanes were not altered by an individual dialysis session. Average plasma CRP values were also higher in HD patients (P < 0.02), but some patients had CRP values that were similar to controls. In the HD patients, total plasma F2-isoprostanes and plasma CRP were correlated (r = 0.48, P = 0.015). Plasma alpha-tocopherol did not differ between patients and controls, but plasma retinol was higher in patients (3.15 +/- 1.71 micromol/L) than in controls (1.97 +/- 0.51 micromol/L, P < 0.05). CONCLUSIONS: These results are consistent with the hypothesis that oxidative stress in ESRD patients contributes to increased values of esterified plasma F2-isoprostanes, with concurrent increases in plasma CRP levels in some patients. Impaired clearance of esterified F2-isoprostanes may contribute to the elevated levels in renal failure. Plasma esterified F2-isoprostanes may be a useful indicator to evaluate effectiveness of interventions to decrease oxidative stress and associated inflammation.

Aged↗
PubMed2001

Oxidative stress and inflammation in hemodialysis patients.

Dialysis is associated with an increased generation of oxidants, which play an important part in the development of endothelial dysfunction and atherogenesis. Markers of oxidative stress include F2-isoprostanes and ethane. Measurements in dialysis patients before dialysis showed higher levels of esterified plasma F2-isoprostanes (1.62 +/- 0.73 ng/mL) than in control subjects (0.27 +/- 0.10 ng/mL) (P < 0.001). Furthermore, levels also correlated with high plasma C-reactive protein (CRP) levels (r =.48, P = 0.015). Breath ethane levels for dialysis patients (N = 19) were 6.32 +/- 3.16 pmol/kg-min, in contrast to 3.08 +/- 1.50 pmol/kg-min in control subjects (N = 11, P < 0.005). Analysis to investigate the relationship between CRP levels and outcome indicated that there was a significant difference in mortality rate over a 3-year period between patients with low and high CRP values (P < 0.001). Patients with high CRP (> 16.8 mg/L) levels were more than twice as likely to die as patients with low CRP levels (relative risk [RR] = 2.16; 95% confidence interval [CI], 1.50-3.09). CRP values were a significant predictor of mortality even after controlling for diabetes, albumin, ferritin, and age at commencement of dialysis. The RR for CRP after adjustment was 1.58 (95% CI, 1.06-2.34, P = 0.024). There were no significant interactions between CRP and other predictors of mortality, indicating that high CRP levels have an additive effect on the mortality risk. These findings show that hemodialysis patients are exposed to both oxidative stress and inflammation.

Acute-Phase Reaction↗
PubMed2001

Effect of ultrafiltration on peripheral urea sequestration in haemodialysis patients.

BACKGROUND: Ultrafiltration (UF) is assumed to enhance urea removal during haemodialysis (HD) because of convective transport and because of contraction of urea distribution volume. However, UF-induced blood volume reduction has been hypothesized to enhance peripheral urea sequestration and post-dialysis urea rebound (PDUR), possibly reducing HD effectiveness. The effect of UF on PDUR was investigated in this study. METHODS: Nine HD patients were studied on two subsequent treatment days. The first HD was performed with UF (UF-rate=0.78+/-0.27 l/h), and the second treatment without UF. Serial measurements of serum water urea nitrogen concentration, arterial blood pressures (BP), and relative blood volume changes (BV%) were obtained over the duration of HD. RESULTS: BP and BV% decreased with UF (BP(sys)= -9%, BP(dia)=-8%, BP(mean)=-9%, BV%=-15%) but increased or remained unchanged without UF (BP(sys)= 9%, BP(dia)=12%, BP(mean)=11%, BV%=1%). PDUR was 28.6+/-9.6% without UF, and increased in every single patient with UF (40.7+/-13.2%, P<0.01). Modelled perfusion of the peripheral low-flow compartment decreased from 1.45+/-0.54 l/min without UF to 0.91+/-42 l/min with UF (P<0.05), thereby explaining an enhanced two-compartment effect and increasing PDUR. CONCLUSION: The significant increase in the two-compartment effect of urea kinetics observed in current HD accompanied by UF can be explained by compensatory, intradialytic blood flow redistribution induced by blood volume reduction. Because of the link between UF and blood flow, limited solute clearance treatment modes that optimize fluid removal such as variable UF will also have favourable effects on delivered dose of dialysis.

Blood Pressure↗
PubMed2001

Consequences of hyperphosphatemia and elevated levels of the calcium-phosphorus product in dialysis patients.

Control of serum phosphorus levels is a central goal in the management of patients with chronic renal failure. Inadequate control of serum phosphorus leads to elevated levels of the calcium-phosphorus product. This plays a pivotal role in vascular calcification, cardiovascular disease, calciphylaxis, and death. Elevated phosphorus and elevated levels of the calcium-phosphorus product are both significant predictors of cardiovascular mortality, at phosphorus and calcium-phosphorus product levels that were considered safe until recently. A lowering of levels such that phosphorus is maintained between 2.2 and 5.5 mg/dl, calcium-phosphorus product is below 55 mg(2)/dl(2), and serum calcium is at 9.2-9.6 mg/dl, respectively, might well be the goal of therapeutic management strategies.

Bone and Bones↗
PubMed2001

The national epidemic of chronic kidney disease. What we know and what we can do.

The alarming increase in the incidence and mortality rate of end-stage renal disease (ESRD) over the past several years has prompted concerned physicians to ask why--and to ponder what can be done to ameliorate the situation. This article, the first in a seven-part series coordinated by the National Kidney Foundation, examines the factors surrounding the epidemic of chronic kidney disease and introduces readers to the organization's new clinical practice guidelines developed through its Kidney Disease Outcomes Quality Initiative. These recommendations emphasize early detection and treatment and offer a new avenue of communication between primary care physicians and nephrologists.

Health Planning↗
PubMed2000

Design and statistical issues of the hemodialysis (HEMO) study.

The Hemodialysis Study is a multicenter clinical trial of hemodialysis prescriptions for patients with end stage renal disease. Participants from over 65 dialysis facilities associated with 15 clinical centers in the United States are randomized in a 2 x 2 factorial design to dialysis prescriptions targeted to a standard dose or a high dose, and to either low or high flux membranes. The primary outcome variable is mortality; major secondary outcomes are defined based on hospitalizations due to cardiovascular or infectious complications, and on the decline of serum albumin. The Outcome Committee, consisting of study investigators, uses a blinded review system to classify causes of death and hospitalizations related to the major secondary outcomes. The dialysis dose intervention is directed by the Data Coordinating Center using urea kinetic modeling programs that analyze results from dialysis treatments to monitor adherence to the study targets, adjust suggested dialysis prescriptions, and assist in trouble-shooting problems with the delivery of dialysis. The study design has adequate power to detect reductions in mortality rate equal to 25% of the projected baseline mortality rate for both of the interventions.

Humans↗
PubMed2000

The dialysis outcomes quality initiative: history, impact, and prospects.

Rigorously developed clinical practice guidelines have the potential to improve patient outcomes. It is toward that end that the National Kidney Foundation (NKF) launched in March 1995 the Dialysis Outcome Quality Initiative (DOQI), an ambitious effort to develop evidence-based clinical practice guidelines for the care of patients with end-stage renal disease (ESRD). Independent, interdisciplinary work groups conducted a structured review of the content and methodologic rigor of all the published literature pertinent to four selected topics: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anemia. Following expert, organizational, and public review, the guidelines were issued in September and October 1997. An implementation plan that called for widespread dissemination of the guidelines and facilitation of adoption of them has resulted in their broad acceptance and Integration into quality improvement efforts. Additional guidelines on nutrition have recently been completed, while others on bone disease, hypertension, and hyperlipidemia are in various stages of planning or development. A major determinant of poor outcome of maintenance dialysis patients is the debilitated state of many individuals with ESRD at the time that they commence dialysis therapy. The recognition of this problem has stimulated an interest in extending the guidelines to management of patients with less severe renal insufficiency, well before they need renal replacement therapy; and to the early detection of renal insufficiency by a proteinuria and albuminuria risk assessment, detection, and elimination (PARADE) program. What started as an initiative to improve the quality of care of dialysis patients has evolved into a considerably expanded effort to making lives better for all individuals with any level of renal insufficiency.

Evidence-Based Medicine↗