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L M Rosales

Publications and source records attributed to L M Rosales.

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Leptin is a negative acute phase protein in chronic hemodialysis patients.

BACKGROUND: Hypoalbuminemia strongly predicts death in hemodialysis patients and results from both inflammation and malnutrition. One potential link between malnutrition and inflammation is appetite suppression triggered by inflammation. Leptin is secreted by adipose tissue and suppresses appetite, and it is also a positive acute phase protein in the rat. Factored for body weight, leptin is known to be increased in hemodialysis patients, but its relationship to inflammation is unknown. METHODS: We examined the relationship between spontaneously occurring activation of the acute phase response and leptin levels in 29 chronic hemodialysis patients. Serum samples were obtained three times weekly for six weeks and then monthly from 29 chronic hemodialysis patients, and the levels of the positive acute phase proteins [C-reactive protein (CRP), alpha1-acid glycoprotein (alpha1 AG), serum amyloid A, ceruloplasmin] and the negative acute phase proteins (albumin and transferrin) as well as leptin and interleukin-6 (IL-6) were measured. RESULTS: Positive and negative acute phase proteins were evaluated at the maximum CRP (mean, 9.42 +/- 1.14 mg/dL) and minimum values (mean, 0.41 +/- 0.09 mg/dL). When CRP was elevated, leptin levels were significantly reduced, as were the negative acute phase proteins albumin and transferrin. Serum amyloid A, ceruloplasmin, alpha1 acid glycoprotein, and IL-6 were all significantly increased at the maximum CRP level, compatible with general activation of the acute phase response. The change in leptin correlated negatively with the change in CRP (R = 0.437, P = 0.018), as did changes in albumin (R = 0.620, P < 0.001). CONCLUSIONS: Leptin is not increased as a consequence of inflammation in hemodialysis patients, but behaves as a negative rather than as a positive acute phase protein. Inflammation is unlikely to reduce appetite in dialysis patients through a leptin-mediated mechanism.

Acute-Phase Proteins↗

The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients. The HEMO Study Group.

BACKGROUND: Cross sectional studies have established that the serum albumin level is dependent on serum levels of acute-phase proteins (APPs) or cytokine levels in hemodialysis patients. While the acute-phase response is generally associated with acute inflammatory events, a cross sectional analysis relating laboratory values to outcomes assumes these values to be unchanging. The longitudinal relationship among laboratory measurements and how they vary over time in a population of patients are unknown. METHODS: Patients who were enrolled in the HEMO Study were recruited into an ancillary longitudinal study to establish the predictive effect of temporal variation in the levels of APPs and of temporal variation in normalized protein catabolic rate (nPCR) on the serum albumin concentration. nPCR was measured monthly using a double-pool method. The positive APPs-C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1-AG), and ceruloplasmin-and the negative APP-transferrin (Trf)-were measured in serum obtained before each dialysis session for six weeks and then monthly in 37 hemodialysis patients. A random coefficient regression analysis was used to assess the association of serum albumin with other measured parameters at each time point, as well as fixed patient characteristics. RESULTS: The within-subject coefficients of variation of albumin (median, range of 25th to 75th percentiles; median, 0.0614; range, 0.0485 to 0.0690) were significantly less than that of APPs (CRP, median, 0.878; range, 0.595 to 1.314, P < 0. 05; and alpha1 AG, median, 0.173; range, 0.116 to 0.247, P < 0.05). The levels of APPs and albumin varied considerably over time. The primary predictor of current albumin was the current CRP level (P = 0.0014). nPCR also was a significant predictor for albumin levels (P = 0.0440) after controlling for the effect of APPs, suggesting an effect of nPCR on serum albumin concentration irrespective of the acute-phase response. Age and the presence of an arteriovenous graft were significant predictors that were associated with reduced albumin. CONCLUSIONS: The acute-phase response is intermittent and is not a continuous feature in individual dialysis patients. Levels of APPs are the most powerful predictors for the levels of albumin concentration in hemodialysis in a longitudinal setting. Since variations in albumin are small, measurement of variations in APPs may provide greater insight into the dynamics of clinically relevant processes.

Acute-Phase Reaction↗

Isothermic hemodialysis and ultrafiltration.

The increase in patient temperature during hemodialysis is explained by hemodynamic compensation during ultrafiltration and hypovolemia that leads to peripheral vasoconstriction and reduced heat losses. We analyzed 51 stable high-efficiency hemodialysis treatments in 27 patients during isothermic dialysis in which body temperature was maintained at a constant level (+/-0.1 degrees C) using the temperature-control option of the Blood Temperature Monitor (BTM; Fresenius Medical Care, Bad Homburg, Germany). Hemodialysis was delivered using ultrapure water (limulus amebocyte lysate test < 0. 06 endotoxin units/mL) at mean blood flows of 410 +/- 40 mL/min. During treatments lasting 178 +/- 23 minutes, 4.8% +/- 1.4% of postdialysis body weight (W%) and 9.5% +/- 2.5% of postdialysis body water were removed using mean ultrafiltration rates of 1.1 +/- 0.3 L/h. Dialysate temperatures significantly decreased from 35.9 degrees C +/- 0.3 degrees C to 35.6 degrees C +/- 0.6 degrees C during hemodialysis. During these treatments, 187 +/- 69 kJ of thermal energy were removed from the patients through the extracorporeal circulation using cool dialysate. Extracorporeal heat flow was 17 +/- 6 W. Energy expenditure (H) estimated from anthropometric data was 65 +/- 12 W. Thus, 28% +/- 10% of estimated energy expenditure (H%) was removed during isothermic dialysis. A highly significant correlation was observed between H% and W% (H% = -5.6 * W%; r(2) = 0.91; P < 0.0001). This result is in support of the volume hypothesis of intradialytic heat accumulation and provides a rule of thumb to estimate extracorporeal cooling requirements for isothermic dialysis. Approximately 6% of H must be removed through the extracorporeal circulation for each percent of ultrafiltration-induced body-weight change. The importance of body temperature control during hemodialysis increases with increased ultrafiltration requirements.

Body Temperature↗

Exercise and extracorporeal blood cooling during hemodialysis.

Intradialytic exercise may improve hemodialysis efficiency. Because exercise interferes with thermal energy and fluid balance, relative blood volume changes (deltaBV%), arterial blood temperatures (T(art)), mean arterial blood pressures, and heart rates (HR) were measured using different dialysate temperatures (Tdia). Four stable patients (age, 49.9 +/- 7.7 years) were studied during 22 treatments that either maintained Tdia at 35.9 degrees C +/- 0.1 degrees C (standard) or provided maximum extracorporeal cooling (cool, Tdia = 34.8 degrees C +/- 0.8 degrees C) in attempts to maintain a constant T(art). Patients exercised for 1 hr at a resistance of 21 +/- 5 W on a stationary bicycle ergometer. Energy expenditure monitored by indirect calorimetry increased from 117 +/- 38 W (baseline) to 338 +/- 116 W (exercise). Mean arterial blood pressures increased by 7 +/- 7 mmHg with cool Tdia, but remained unchanged (-1 +/- 4 mmHg) with standard Tdia (p < 0.05). However, the increase in T(art) was smaller with cool (0.1 degrees C +/- 0.3 degrees C) than with standard (0.3 degrees C +/- 0.2 degrees C) Tdia (p < 0.05). The larger increase in O2 uptake per change in HR (68 +/- 56 vs 38 +/- 17 ml/beat) indicated an increase in stroke volume when cool dialysate was used (p = NS). Exercise produced a small (0.95% +/- 0.95%), but significant, decrease in deltaBV% that reversed at the end of exercise. Intradialytic exercise was well tolerated, especially when Tdia was lowered such that hemodynamic stress to dissipate excess heat through the cutaneous circulation was reduced and blood pressure stability was improved.

Blood Volume↗