Tracking Arteriovenous Fistula Maturation: A Novel Approach.

BACKGROUND: The time between the creation of an arteriovenous fistula (AVF) and its successful use is significantly longer in hemodialysis (HD) patients in the United States compared to those in other countries, and there is an urgent need to reduce the residence time of central-venous catheters (CVC). METHODS: Successful AVF creation and maturation results in typical hemodynamic changes, such as an increase in cardiac output and upper body blood flow (UBBF). In patients with CVC as vascular access, we measured once per minute intradialytic central-venous oxygen saturation (ScvO2) and hemoglobin levels simultaneously using the Crit-Line Monitor. Under conditions of stable upper body oxygen consumption and arterial oxygen saturation, ScvO2 and hemoglobin concentration allows the calculation of estimated UBBF (eUBBF). In a quality improvement project, we used ScvO2 and eUBBF to track the hemodynamic changes accompanying AVF maturation. RESULTS: Out of 11 patients (9 incident to HD, 1 female, age 61 ± 13 years), AVF maturation was successful in 9. In 1 patient, the AVF did not mature. One patient died from sudden cardiac death with a maturing AVF. In the 9 patients with successful AVF maturation, ScvO2 increased from 60.9 ± 2.7% prior to AVF creation to 73.4 ± 3.6% a week after AVF creation (19.6 ± 6.3% increase). eUBBF increased from 1.3 ± 0.3 to 2.2 ± 0.6 L/min (62.7 ± 37.5% increase); no material ScvO2 or eUBBF changes occurred in the other 2 patients. CONCLUSION: Our results indicate the potential utility of ScvO2 and eUBBF to track the hemodynamic response to AVF maturation. To what extent these insights translate into shortening of the time between AVF creation and successful cannulation warrants further investigations.

Plasma Gelsolin and Its Association with Mortality and Hospitalization in Chronic Hemodialysis Patients.

BACKGROUND: Human plasma gelsolin (pGSN) is an actin-binding protein that is secreted into the extracellular fluid, with the skeletal muscle and myocardial tissues being its major source. Depletion of pGSN has been shown to be related to a variety of inflammatory and clinical conditions. METHODS: pGSN levels were prospectively determined in prevalent maintenance hemodialysis (HD) patients from 3 U.S. dialysis centers. Demographics (age, time since dialysis initiation, race, gender, body height and weight, comorbidities), inflammatory markers (C reactive protein, CRP; interleukin 6, IL-6), free triiodothyronine (fT3), and routine laboratory parameters were obtained. We performed Kaplan-Meier and Cox proportional hazard survival analysis for all-cause and cardiovascular mortality, and recurrent event survival analysis for hospitalization. RESULTS: We studied 153 patients; mean age was 60.5 ± 14.7; 52% were males. The mean pGSN level was 6,617 ± 1,789 mU/ml. In univariate analysis, pGSN was positively correlated with body mass index (r = 0.2, p = 0.01), pre-HD serum albumin (r = 0.247, p = 0.002), and pre-HD serum creatinine (r = 0.381, p < 0.001), and inversely with age (r = -0.286, p < 0.001), CRP (r = -0.311, p < 0.001), and IL-6 (r = -0.317, p < 0.001). In the adjusted analysis, the associations with CRP and creatinine were retained. pGSN levels tended to be lower in patients who died (p = 0.08). There was no association with all-cause or cardiovascular mortality, or all-cause hospitalization. Of note, fT3 was lower in patients who died (p = 0.001). CONCLUSIONS: Even though pGSN was inversely correlated with age, CRP and IL-6, suggesting that inflammation may influence pGSN, lower pGSN levels were not associated with hospitalization, all-cause and cardio-vascular mortality in this patient population.

Effect of ultrafiltration on thermal variables, skin temperature, skin blood flow, and energy expenditure during ultrapure hemodialysis.

The cause of the increase in core temperature (CT) during hemodialysis (HD) is still under debate. It has been suggested that peripheral vasoconstriction as a result of hypovolemia, leading to a reduced dissipation of heat from the skin, is the main cause of this increase in CT. If so, then it would be expected that extracorporeal heat flow (Jex) needed to maintain a stable CT (isothermic; T-control = 0, no change in CT) is largely different between body temperature control HD combined with ultrafiltration (UF) and body temperature control HD without UF (isovolemic). Consequently, significant differences in DeltaCT would be expected between isovolemic HD and HD combined with UF at zero Jex (thermoneutral; E-control = 0, no supply or removal of thermal energy to and from the extracorporeal circulation). During the latter treatment, the CT is expected to increase. In this study, changes in thermal variables (CT and Jex), skin blood flow, energy expenditure, and cytokines (TNF-alpha, IL-1 receptor antagonist, and IL-6) were compared in 13 patients, each undergoing body temperature control (T-control = 0) HD without and with UF and energy-neutral (E-control = 0) HD without and with UF. CT increased equally during energy-neutral treatments, with (0.32 +/- 0.16 degrees C; P = 0.000) and without (0.27 +/- 0.29 degrees C; P = 0.006) UF. In body temperature control treatments, the relationship between Jex and UF tended to be significant (r = -0.51; P = 0.07); however, there was no significant difference in cooling requirements regardless of whether treatments were done without (-17.9 +/- 9.3W) or with UF (-17.8 +/- 13.27W). Changes in energy expenditure did not differ among the four treatment modes. There were no significant differences in pre- and postdialysis levels of cytokines within or between treatments. Although fluid removal has an effect on thermal variables, no single mechanism seems to be responsible for the increased heat accumulation during HD.

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.

Relationships among inflammation nutrition and physiologic mechanisms establishing albumin levels in hemodialysis patients.

BACKGROUND: Serum albumin concentration is a balance among its synthesis rate, fractional catabolic rate (FCR), distribution, dilution in the plasma pool and external loss. The physiologic bases for establishing the level of serum albumin in hemodialysis patients have not been defined despite the association of hypoalbuminemia with excess mortality. Albumin concentration is associated with the levels of several acute phase proteins (APPs), C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1 AG), or ceruloplasmin, and with nutritional markers, such as normalized protein catabolic rate (nPCR). METHODS: To establish the relationship among parameters that regulate albumin levels and markers of nutrition and inflammation, we injected [125I]-albumin, into 64 hemodialysis patients enrolled in the HEMO study to measure albumin distribution, synthesis and FCR. These variables were related to the levels of acute phase proteins (APPs), nPCR, body mass index (BMI), external albumin loss as well as demographic variables. Albumin distribution, synthesis and FCR were calculated from kinetic modeling, as was the initial plasma volume (PV). Serum albumin, transferrin, CRP, ceruloplasmin and alpha1 AG were measured weekly. Dialysate was collected during one dialysis each week to measure albumin loss. Results were analyzed by multiple linear regression. RESULTS: Albumin concentration correlated with its synthesis rate and FCR, but not with PV or its distribution between the vascular and extravascular pools. Albumin concentration also correlated with nPCR and alpha1 AG. However, albumin synthesis was directly related most strongly to PV and BMI (or nPCR), but not to levels of APPs. By contrast, albumin FCR correlated positively with both alpha1 AG and ceruloplasmin. CONCLUSION: Albumin concentration in dialysis patients changes with inflammation and nutritional status through their effects on albumin catabolism and synthesis, respectively. Within the range of albumin levels in these patients, nutritional variables primarily affected albumin synthesis while inflammation caused hypoalbuminemia by increasing albumin FCR. Albumin synthesis also increased in proportion to PV. The result of this is that PV expansion does not contribute to hypoalbuminemia.