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Biomedical subjects

N W Levin

Publications and source records attributed to N W Levin.

At least 19 recordsLinked to original sources
PubMed2001

Levels of alpha1 acid glycoprotein and ceruloplasmin predict future albumin levels in hemodialysis patients.

BACKGROUND: Serum albumin concentration predicts mortality in hemodialysis (HD) patients. While serum albumin concentration correlates with serum concentration of C-reactive protein (CRP) and is dependent upon CRP in multiple regression models in cross sectional studies, CRP does not predict future albumin levels, possibly because CRP changes rapidly, yielding large month-to-month variability in CRP. If inflammation causes rather than is simply associated with hypoalbuminemia, then changes in the levels of acute phase proteins should precede changes in serum albumin concentration. METHODS: The levels of long-lived positive and negative acute-phase proteins (APPs) (C-reactive protein, ceruloplasmin, alpha1 acid glycoprotein, transferrin and albumin) were measured longitudinally in 64 HD patients and a regression model was constructed to predict future albumin levels. Normalized protein catabolic rate (nPCR) was measured monthly. The number of repeated measurements ranged from 9 to 39 in each patient (median 22 and a mean of 23 measurements). To construct a model that would predict serum albumin concentration at any time j, values of all longitudinally measured APPs, positive and negative at any time j - 1, approximately 30 days prior to time j, were used. Other demographic factors (such as, race, access type, and cause of renal failure) also were incorporated into the model. RESULTS: The model with the best fit for predicting serum albumin at time j included albumin, ceruloplasmin, and alpha1 acid glycoprotein measured at time j - 1. The only demographic variable with subsequent predictive value was diabetes. CONCLUSIONS: The finding that changes in the concentration of the long lived APPs measured one month earlier are associated with predictable changes in the future concentration of serum albumin suggest that changes in inflammation are likely to be causal in determining serum albumin concentration in hemodialysis patients.

Adult↗
PubMed2001

Inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients.

BACKGROUND: Cross-sectional studies have shown an inverse correlation between serum C-reactive protein (CRP) and serum albumin concentration in hemodialysis patients. The net effects of inflammation and dietary protein intake on nutritional markers over time are unknown. METHODS: To explore the effects of CRP and normalized protein catabolic rate (nPCR) on serum albumin and creatinine, we analyzed six consecutive months of laboratory data from 364 hemodialysis patients, using a multivariable Mixed model with conservative biases. RESULTS: The overall trend over time in serum albumin was slightly positive (0.039 g/dL/month) and in serum creatinine slightly negative (-0.052 mg/dL/month). With increasing CRP, serum albumin declined significantly (-0.124 g/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes, and nPCR, P < 0.0001). Serum albumin increased with increasing nPCR (0.021 g/dL/month per 0.1 g/kg/day, P < 0.0001). The effect of CRP on albumin was attenuated in African Americans and at a higher nPCR. Corresponding values for creatinine mirrored those for albumin. With increasing CRP, creatinine declined significantly [-0.142 mg/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes (time since initiation of dialysis; vintage), Kt/V, and nPCR, P = 0.002]. Serum creatinine increased with increasing nPCR (0.183 mg/dL/month per g/kg/day, P < 0.0001). CONCLUSIONS: Proxies of inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients. These data provide a rationale for prospective testing of dietary protein supplementation in hemodialysis patients with biochemical evidence of ongoing inflammation and "malnutrition."

Adult↗
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↗