The main objective of this thesis is to contribute to the prevention and control of the cardiovascular risk, hydration state and nutritional state in dialysis patients using non-invasive electrical impedance measurements. The thesis is structured in three parts with the following objectives: 1) to establish electrical impedance reference data for healthy Cuban population, 2)to improve the diagnostic based on impedance methods in Cuban hemodialysis (HD)patients and 3) to develop the impedance methods for continuous ambulatory peritoneal dialysis patients (CAPD).Healthy population: We analyzed the impedance vector distribution using the Bioimpedance Vector Analysis (BIVA) for the three more representative race-ethnicities in Cuba. We measured 1196 healthy adult (689 M, 507 W, 18-70 yr). The 95% confidence ellipses were drawn using specific BIVA software for mean vectors of different races. Due to the close distribution of mean vectors that we found for the three race-ethnicities, we concluded that only one set of sex-specific tolerance ellipses can be used for the Cuban population.HD patients: The BIVA method was used in a sample of 74 HD patients in stable (without edema) and critical (hyper-hydrated and malnutrition) states in order to establish the relation between hyper-hydration and mortality. Stable group include 48 patients (28 M and 18 W), and critical group include 28 critical patients (16 M and 12 W). Student's t test and Hotelling's T2 test were used to analyse the separation of groups obtained by means of clinical diagnosis and those obtained by BIVA. A statistically significant difference was obtained (P < 0.05) in R/H, Xc/H and phase angle, PA. Critical patients (hyper-hydrated and malnutrition) were located below the inferior pole of the 75% tolerance ellipse, with PA lower than 4º. In conclusion, the BIVA method could be used to detect hyper-hydration state before edema appears, and to predict survival through PA. Advantages of the method are its simplicity, objectivity and that it does not require the definition of a patient dry weight.CAPD patients: Segmental impedance measurements were obtained using 9 configurations (7 longitudinal and 2 transversal) in 25 CAPD male patients.In a first study we analyzed Z, Z/H and ZBMI indexes. 23 male patients were classified according to the hydration state as normo-hydrated, group 0 (10 M) or hyper-hydrated, group 1 (13 M). Wilcoxon test was used to analyze the change in impedance produced by a PD session. Mann-Whitney U test was used to analyse the separation between groups obtained by means of clinical diagnosis and those obtained by Z, Z/H or ZBMI. Spearman correlation was used to study the correlation between impedance vectors in each segment and clinical assessment. Statistical significance was set at P < 0.05. Results show that ZBMI gives information about the specific resistivity of tissues and not about fluid and fat mass changes. BIVA separate hyper-hydrated and normo-hydrated patients. Transversal measurements in the leg region and longitudinal in the thorax region are useful to corroborate the hydration and nutritional state in CAPD patients.In a second study a new classification was performed. Group 0 has normo-hydrated patients (10 M) and group 1 includes patients (15 M) with varying degrees of hypertension, overhydration and high score on cardiovascular risk factors. Mann-Whitney U-test was used to compare the differences in clinical measurements, laboratory test, and bioimpedance measurements between groups. The Mahalanobis Distance (dM2) was calculated using a bidimensional space, using the resistance measurement, right-side (RRS/H) or thorax segment (RTH/H) and the BPmean. Hotelling's T2 test was used to analyzed difference between groups through (RTH/H, BPmean) and (RRS/H, BPmean) vectors. A statistically significant difference was obtained (P < 0.05) in both vectors. Group 1 showed a small dM2 with respect to a reference patient (a critical patient with acute lung oedema) with high BPmean and low values of RTH/H and RRS/H. Moreover, Group 0 showed a larger dM2 with respect to the reference patient with lower BPmean and higher values of RTH/H and RRS/H. All patients classified as hyper-hydrated leading to hypertension by clinical assessment were correctly classified using dM2(RTH/H, BPmean). We conclude that segmental bioimpedance of the thoracic region could be a simple, objective, non-invasive method of support to facilitate the clinical assessment in CAPD.

Volume overload is a common feature in patients on haemodialysis (HD). This contributes significantly to the cardiovascular disease burden seen in these patients. Clinical assessments of the volume state are often inaccurate. Techniques such as interdialytic blood pressure, relative blood volume monitoring, bioimpedance are available to improve clinical effectives. However all these techniques exhibit significant shortcomings in their accuracy, reliability and applicability at the bed side. We evaluated the usefulness of a dual compartment monitoring technique using Continuous Segmental Bioimpedance Spectroscopy (CSBIS) and Relative Blood Volume (RBV) as a tool to assess hydration status and determine dry weight. We also sought to evaluate the role of Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP) as a volume marker in dialysis patients. The Retrospective analysis of a historical cohort (n = 376, 55 Diabetic) showed a significant reduction in post-dialysis weights in the first three months of dialysis (72.5 to 70kg, p<0.027) with a non-significant increase in weight between months 6-12. The use of anti-hypertensive agents reduced insignificantly in the first 3 months, increased marginally between months 3-6 and significantly increased over the subsequent 6 months. The residual urea clearance (KRU) fell and dialysis times increased. The cohort was very different to that dialysing at Tassin and showed a dissociation between weight reduction and BP control. This may relate to occult volume overload. CSBIS-RBV monitoring in 9 patients with pulse ultrafiltration (pulse UF) showed distinct reproducible patterns relating to extra cellular fluid (ECF) and RBV rebound. An empirical Refill Ratio was then used to define the patterns of change and this was related to the state of their hydration. A value closer to unity was consistent with the attainment of best achievable target weight. The refill ratio fell significantly between the first (earlier) and third (last) rebound phase (1.97 ± 0.92 vs 1.32 ± 0.2). CSBIS monitoring was then carried out in 31 subjects, whilst varying dialysate composition, temperature and patient posture to analyse the effects of these changes on the ECF trace and to ascertain whether any of these interventions can trigger a change in the slope of the ECF trace distinct to that caused by UF. Only, isovolemic HD caused a change in both RBV and ECF in some patients that was explained by volume re-distribution due to gravitational shifts, poor vascular reactivity, sodium gradient between plasma and dialysate and the use of vasodilating antihypertensive agents. This has not been described previously. These will need to be explored further. The study did demonstrate a significant lack of comparability of absolute values of RECF between dialysis sessions even in the same patient. This too has not been described previously. This is likely to be due to subtle changes in fluid distribution between compartments. Therefore a relative changes must be studied. This sensitivity to subtle changes may increase the usefulness of the technique for ECF tracking through dialysis. The potential of dual compartment monitoring to track volume changes in real time was further explored in 29 patients of whom 21 achieved weight reductions and were able to be restudied. The Refill Ratio decreased significantly in the 21 patients who had their dry weights reduced by 0.95 ± 1.13 kg (1.41 ± 0.25 vs 1.25 ± 0.31). Blood pressure changes did not reach statistical significance. The technique was then used to examine differences in vascular refill between a 36oC and isothermic dialysis session in 20 stable prevalent patients. Pulse UF was carried out in both these sessions. There were no significant differences in Refill Ratios, energy removed and blood pressure response between the two sessions. The core temperature (CT) of these patients was close to 36oC and administering isothermic HD did not confer any additional benefit. Mean BNP levels in 12 patients during isovolemic HD and HD with UF did not relate to volume changes. ANP concentrations fell during a dialysis session in 11 patients from a mean 249 ± 143 pg/ml (mean ± SD) at the start of dialysis to 77 ± 65 pg/ml at the end of the session (p<0.001). During isolated UF levels did not change but fell in the ensuing sham phase indicating a time lag between volume loss and decreased generation. (136±99 pg/ml to 101±77.2 pg/ml; p<0.02) In a subsequent study ANP concentrations were measured throughout dialysis and in the post-HD period for 2 hours. A rebound in ANP concentration was observed occurring at around 90 min post-HD. The degree of this rebound may reflect the prevailing fluid state and merit further study. We have shown the utility of dual compartment monitoring with CSBIS-RBV technique and its potential in assessing volume changes in real time in haemodialysis patients. We have also shown the potential of ANP as an independent marker of volume status in the same setting. Both these techniques merit further study.