Laura Rosales

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 (KpwiP) and time average plasma iP concentration (TACiP) and treatment time (t); a new iP concentration parameter (nTACiP, the TACiP normalized to predialysis CoiP) was devised and shown to be a highly predictable function of the form nTACiP = 1 – α(1 – exp[–βKpwiP· t/ViP]), where the coefficients α and β are calculated for each patient from 2 measure values for nTACiP, KpwiP·t/ViP early and late in dialysis; we measured 8–10 serial values for nTACiP, KpwiP· t/ViP over a single dialysis in 23 patients; the expression derived for iP mass balance is ΔTiP = 12(PCR) – [KpwiP(t) (N/7)][CoiP(1 – α(1 – exp[–β(Kt/ViP)]))] – kb·Nb. Results: Calculated nTACiP = 1.01(measured nTACiP), 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.

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.

Effective diffusion volume flow rates (Qe) for urea, creatinine, and inorganic phosphorous (Qeu, Qecr, QeiP) during hemodialysis.

In vivo solute clearances can be estimated from dialyzer blood (Qb) and dialysate (Qd) flow rates and a solute‐ and dialyzer‐specific overall permeability membrane area product (KoA). However, these calculations require knowledge of the flow rate of the effective solute distribution volume in the flowing bloodstream (Qe) in order to calculate in vivo clearances and KoAs. We have determined Qe for urea, creatinine, and inorganic phosphorus from changes in concentrations across the blood compartment and mass balance between the blood and dialysate streams. We made four serial measurements over one dialysis in 23 patients and found that Qeu equals the total blood water flow rate, Qecr equals the plasma water flow rate plus 61% of red cell water flow rate, and QeiP is limited to the plasma water flow rate. Equations are derived to calculate Qe for each of these solutes from Qb and hematocrit and in vivo KoAs for each solute were calculated.

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.

Saliva urea dipstick test: application in chronic kidney disease.

BACKGROUND A noninvasive test for determining elevated levels of blood urea nitrogen (BUN) may be useful under circumstances in which there is limited access to laboratories. Because saliva urea nitrogen (SUN) parallels BUN, we investigated the diagnostic performance of a semiquantitative SUN dipstick to test for elevated BUN levels in patients with chronic kidney disease (CKD). MATERIALS AND METHODS Patients with CKD Stages 1 to 5D were studied. 50 µl of saliva were transferred onto the SUN test strip (Integrated Biomedical Technology, Elkhart, Indiana, IN, USA). SUN was determined after 1 minute by visual comparison of the color of the moistened test pad with 6 calibrated color blocks. Interobserver reproducibility was evaluated by independent observers, masked to urea concentrations of 6 calibrated urea solutions. Correlation between SUN and BUN was quantified by Spearmans rank correlation coefficient (RS), Kappa Statistic was employed to evaluate within-sample reproducibility of duplicates. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of SUN. RESULTS 68 patients (31 females, 60 ± 14 years; 34 hemodialysis patients, 34 patients CKD Stages 1 - 4) were studied. Interobserver coefficient of variation was 4.9% at SUN levels > 50 mg/dl; within-sample reproducibility was 90%. SUN and BUN were correlated significantly (RS = 0.63; p < 0.01). Elevated BUN was diagnosed with high accuracy by SUN determination (area under the ROC curve: 0.90 (95% CI 0.85 - 0.95)). CONCLUSION Semiquantitative dipstick measurements of SUN can reliably identify CKD patients with elevated BUN levels.

Comparison of Bioimpedance Techniques to Detect Changes in Fluid Status in Hemodialysis Patients

Background: Bioimpedance (BI) is maturing as a clinical technique for assessing fluid volume status. The aim of this study was to compare the sensitivity of four BI methods to detect changes in fluid status in hemodialysis patients. Methods: Forty-five patients were studied twice in the same week, i.e. once after the long and short interdialytic intervals, respectively. The four BI methods used were: (a) calf normalized resistivity (CNR) at a 5-kHz frequency, (b) whole-body multifrequency BI spectroscopy (MF-BIS) to estimate the normal hydration weight (NHWWBM), (c) whole-body MF-BIS to estimate the ratio of extracellular volume to total body water (wECV/wTBW), and (d) whole-body single-frequency (50 kHz) BI analysis to compute the ratio of ECV (sfECV) to TBW (sfTBW). Results: The relationship (slope of the regressive line) between relative changes (%) in the above mentioned four BI parameters and differences in weight (kg) was most pronounced with CNR (5.2 ± 1.6%/kg), followed by wECV/wTBW (1.7 ± 0.7%/kg) and NHWWBM (0.73 ± 0.2%/kg). Changes in sfECV/sfTBW and differences in weight were not correlated. Conclusions: CNR is more sensitive than whole-body BIS for detecting differences in fluid status.

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.

Techniques for assessing fluids status in patients with kidney disease.

Purpose of reviewThe aim of this article is to present current information on techniques for fluid status assessment in patients with kidney disease. The methods can be broadly categorized into biomarkers, ultrasound, blood volume monitoring, and bioimpedance. Recent findingsBiomarkers including atrial natriuretic peptide and B-type natriuretic peptide have been shown to provide information about relative changes in fluid status. Ultrasound is applied to measure inferior vena cava indices, pulmonary indicators, and vascular indicators of fluid overload. Relative blood volume monitoring is used to measure change in intravascular fluid during hemodialysis. While in principle appealing, measurement of absolute blood volume has seen limited use to date. Bioimpedance techniques such as vector analysis, whole body, and regional bioimpedance spectroscopy, have shown their ability to estimate fluid status. SummaryThe interpretation of biomarkers is complicated by the presence of cardiac disease. All ultrasound methods have some correlation with fluid status; however, operator dependency limits their routine use. Bioimpedance methods and relative blood volume monitoring are increasingly used to assess fluid status in patients with acute or chronic kidney disease. Measurement of absolute blood volume holds promise for the future.

Validation of the Blood Temperature Monitor for Extracorporeal Thermal Energy Balance during in vitro Continuous Hemodialysis

Continuous renal replacement therapies (CRRT) are today considered a well-tolerated and efficient group of treatments for acute renal failure in critically ill patients [1–12]. The evolution in technology of CRRT has only partially followed the more sophisticated evolution that took place in the equipment for chronic hemodialysis patients. In such patients, the increased morbidity and the progressively increased age, require a gentle and carefully monitored hemodialysis therapy. To achieve such results, on-line monitoring techniques have been developed including urea sensors, temperature sensors, blood volume sensors and biofeedback systems [13]. We will try to analyze how this new technology could have a positive impact in acute patients and how it could be implemented in the present equipment for CRRT [14–16].

Early Systolic Blood Pressure Changes in Incident Hemodialysis Patients Are Associated with Mortality in the First Year

Background: In incident hemodialysis (HD) patients, the relationship between early systolic blood pressure (SBP) dynamics and mortality is unknown. Methods: Baseline SBP levels were stratified into 5 categories ranging from <120 and ≥180 mm Hg. Early pre-HD SBP change was defined as the slope of pre-HD SBP from week 1 to 12 and categorized in quartiles (Q1, lowest slope). SBP slopes were computed for each patient by simple linear regression. Results: In 3,446 incident HD patients (42% females, 44% black, age 62 ± 15 years), the median pre-HD SBP slope was –1.7 (Q1) to +2.3 (Q4) mm Hg/week. In an adjusted multivariate Cox regression analysis, patients with declining SBP (slope Q1) had higher mortality compared to patients with increasing pre-HD SBP (slope Q4) at 12 months (hazard ratio 2.01, 95% confidence interval 1.35–3.01). In addition, patients with baseline pre-HD SBP <120 mm Hg showed higher mortality compared to the reference group (SBP ≥180 mm Hg) at 12 months (hazard ratio 1.89, 95% confidence interval 1.03–3.45). Conclusion: Baseline pre-HD SBP and early SBP dynamics are associated with mortality in the first year of dialysis. Patients who had low (pre-HD SBP <120 mm Hg) or declining SBP had the highest mortality rates. Particular attention is warranted in incident HD patients with low or declining SBP.