[Cardionephrology: past, present and future]. / Cardionefrologia: passato, presente e futuro.

In 1987, the first Kidney-Heart meeting was held in Assisi, Italy and in 1991 the term Cardionephrology was coined in medical practice. Since then, nephrologists and cardiologists realized the utility of a tight cooperation among them and organized an agenda of scientific meetings which take place every two years within European countries. The cooperation was strengthened by daily observation which shows renal replacement therapy had solved many problems but imposed or added new disorders to cardiovascular system. Soon, the nephrologists learned that hemodialyisis techniques had not only blood detoxification effect but also cardiovascular consequences. Therefore, the nephrologists started to adopt cardiological tools and apply them to renal patients. The cardiologists realized that in some aspects kidney patients are different from non-renal cardiological patients and have to be treated differently. In Assisi Cardionephrology meetings a clear message was launched: the necessity to bring nephrologists and cardiologists together with the potential benefit of learning from others experiences and transferring the outcome for the benefit of our patients. As result, many foundations and journals have been emerged on this topic. Is there a future for Cardionephrolgy? The answer is yes, with a unique limitation: to continue the spirit of Assisi, following the culture of cooperation and relying on RCTs hypothesis.

Significance of interdialytic weight gain versus chronic volume overload: consensus opinion.

Predialysis volume overload is the sum of interdialytic weight gain (IDWG) and residual postdialysis volume overload. It results mostly from failure to achieve an adequate volume status at the end of the dialysis session. Recent developments in bioimpedance spectroscopy and possibly relative plasma volume monitoring permit noninvasive volume status assessment in hemodialysis patients. A large proportion of patients have previously been shown to be chronically volume overloaded predialysis (defined as >15% above 'normal' extracellular fluid volume, equivalent to >2.5 liters on average), and to exhibit a more than twofold increased mortality risk. By contrast, the magnitude of the mortality risk associated with IDWG is much smaller and only evident with very large weight gains. Here we review the available evidence on volume overload and IDWG, and question the use of IDWG as an indicator of 'nonadherence' by describing its association with postdialysis volume depletion. We also demonstrate the relationship between IDWG, volume overload and predialysis serum sodium concentration, and comment on salt intake. Discriminating between volume overload and IDWG will likely lead to a more appropriate management of fluid withdrawal during dialysis. Consensually, the present authors agree that this discrimination should be among the primary goals for dialysis caretakers today. In consequence, we recommend objective measures of volume status beyond mere evaluations of IDWG.

Treatment frequency and efficiency in hemodiafiltration.

BACKGROUND: One of the main objectives of dialysis is uremic retention product elimination. Efficiency of dialysis modalities varies both regarding the range of solutes removed and the extent of such removal. We analyzed plasma (or blood) concentrations of marker solutes in intermittent treatment schedules using hemodiafiltration (HDF). METHODS: Elimination and rebound of uremic solutes were measured in 10 patients (77 ± 12 kg, 66.5 ± 9.2 years) treated with postdilution HDF in one 4-hour treatment and in two 2-hour treatments on consecutive days (Polyflux 2.1 m(2), QB 451 ± 53 ml/min, QD 598 ± 13 ml/min). Blood urea, creatinine, phosphate, ß2-microglobulin, complement factor D and advanced glycation end products were analyzed before, during and after HDF for 24-48 h. RESULTS: Applying two 2-hour HDF treatments on consecutive days resulted in significantly lower plasma (or blood) levels of urea, creatinine, phosphate, ß2-microglobulin, and advanced glycation end products after 48 h than using one 4-hour session. CONCLUSIONS: Increased treatment frequency could further optimize blood purification in HDF therapy.

Geographical variability of patient characteristics and treatment patterns affect outcomes for incident hemodialysis patients.

BACKGROUND: Geographical differences in disease prevalence and mortality have been described in the general population and in chronic kidney disease patients in Europe. In this secondary analysis of the Membrane Permeability Outcome (MPO) study, we addressed differences in patient and treatment patterns, and whether these affect patient outcomes. METHODS: Participating countries were grouped according to geographical location; thus study centers in France, Greece, Italy, Portugal and Spain were allocated to southern Europe (n=499), and those in all other countries (Belgium, Germany, Poland and Sweden) to northern Europe (n=148). Descriptive analysis of patient and treatment patterns at study start, as well as survival analysis, was performed. RESULTS: In patients from the northern European countries, a higher prevalence of diabetes mellitus and of cardiovascular disease was observed than in those from southern Europe (diabetes 35.1% vs. 21.0%, p=0.0007; cardiovascular disease 40.5% vs. 22.8%, p<0.0001). In northern Europe, 23% of patients started hemodialysis with a catheter for vascular access, while in southern European centers, only 13% did so (p=0.0042). Kaplan-Meier survival analysis revealed a lower probability for both all-cause and cardiovascular mortality in southern Europe (log-rank test p<0.001). In a Cox proportional hazards model, a higher mortality risk was estimated for the northern European patients after adjustment for age, sex, membrane permeability, comorbidity index and vascular access (hazard ratio = 1.831; 95% confidence interval, 1.282-2.615; p=0.0009). CONCLUSIONS: Our study patients from northern Europe showed a higher risk profile than those from southern Europe. However, only some of the factors can be modified in attempts to lower the mortality risk in this geographical area.

Importance of normohydration for the long-term survival of haemodialysis patients.

BACKGROUND: Fluid overload and hypertension are among the most important risk factors for haemodialysis (HD) patients. The aim of this study was to analyse the impact of fluid overload for the survival of HD patients by using a selected reference population from Tassin. METHODS: A positively selected HD population (n = 50) from Tassin (Lyon-France) was used as a reference for fluid status and all-cause mortality. This population was compared to one dialysis centre from Giessen (Germany) which was separated into a non-hyperhydrated (n = 123) and a hyperhydrated (n = 35) patient group. The hydration status (ΔHS) of all patients was objectively measured with whole-body bioimpedance spectroscopy in 2003. All-cause mortality was analysed after a 6.5-year follow-up. RESULTS: Most of the reference patients from Tassin were normohydrated (ΔHS = 0.25 ± 1.15 L) at the start of the HD session. The hydration status of the Tassin patients was not different to the non-hyperhydrated Giessen patients (ΔHS = 0.8 ± 1.1 L) but significantly lower than in the hyperhydrated Giessen group (ΔHS = 3.5 ± 1.2 L). Multivariate adjusted all-cause mortality was significantly increased in the hyperhydrated patient group (hazard ratio = 3.41)- no difference in mortality could be observed between the Tassin and the non-hyperhydrated group from Giessen-even considering the fact that Tassin patients presented a significantly lower blood pressure. CONCLUSIONS: Fluid overload has a very high predictive value for all-cause mortality and seems to be one of the major killers in the HD population. Patients might strongly benefit from active management of fluid overload.

Acetate-free biofiltration reduces intradialytic hypotension: a European multicenter randomized controlled trial.

BACKGROUND: Intradialytic hypotension (IH) is a common complication of bicarbonate hemodialysis (BD) and contributes to the intolerance of dialysis and the high cardiovascular morbidity and mortality among dialysis patients, the risk of which can be contained by convective therapies. AIMS/METHODS: To assess whether acetate-free biofiltration (AFB), a hemodiafiltration technique found to improve intradialytic cardiovascular stability in short-term studies, can influence long-term IH rates, predialysis systolic blood pressure (SBP), cardiovascular morbidity and mortality by comparison with BD, we analyzed data from a randomized controlled trial enrolling 371 new-to-dialysis patients, 194 on BD and 177 on AFB. RESULTS: During a 3-year follow-up, AFB carried a significantly lower risk of IH (incidence rate ratio 0.60 (95% CI 0.53-0.68), p < 0.0001). SBP dropped on AFB (p = 0.01), while it did not change on BD. Cardiovascular morbidity and mortality were similar between AFB and BD. CONCLUSION: AFB carries a lower long-term IH rate and reduces SBP by comparison with BD.

Therapeutic equivalence of epoetin zeta and alfa, administered subcutaneously, for maintenance treatment of renal anemia.

INTRODUCTION: The primary objective of the trial was to prove the therapeutic equivalence of epoetin zeta to epoetin alfa when administered subcutaneously for maintaining target hemoglobin (Hb) in patients with renal anemia on chronic hemodialysis. Additional information was provided on the safety and tolerability of epoetin zeta with particular focus on the formation of anti-erythropoietin antibodies. METHODS: A total of 462 patients were randomized to either epoetin zeta or alfa for 28 weeks after an open period of dose adjustment of 12-16 weeks with only epoetin zeta. The aim of treatment was to maintain Hb between 10.0-12.0 g/dL with constant epoetin dosage. Primary endpoints were the mean Hb level and the mean weekly epoetin dosage during the last 4 weeks of treatment. Safety endpoints were the occurrence of anti-erythropoietin antibodies, incidence of Hb levels above 13 g/dL, ratings of tolerability, and adverse events (AEs). RESULTS: The mean Hb level (+/-SD) during the last 4 weeks of treatment was 10.94+/-0.84 g/dL (epoetin zeta) and 11.02+/-0.94 g/dL (epoetin alfa). The 95% confidence interval (CI) (''C0.28 g/dL to 0.12 g/dL) was entirely within the predefined equivalence range (+/-0.5 g/dL). The mean weekly epoetin dosage per body weight over the last 4 weeks of treatment was 97.0+/-94.3 IU/kg/week (epoetin zeta) and 86.0+/-78.0 IU/kg/week (epoetin alfa). The 95% CI (''C8.06 IU/kg/week to 29.96 IU/kg/week) was also within the predefined equivalence range of +/-45 IU/kg/week. The most common AEs were infections and infestations (15.1% of patients on epoetin zeta and 14.8% of patients on epoetin alfa). None of the patients developed anti-erythropoietin antibodies. CONCLUSIONS: Epoetin zeta, administered subcutaneously, is equivalent to epoetin alfa in respect of its clinical efficacy. The safety profile of both products is similar: no unexpected AEs were observed, no patients developed anti-erythropoietin antibodies, and both epoetin preparations were well tolerated.

Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy.

Using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS), we determined incidence, prevalence, and outcomes among hemodialysis patients with atrial fibrillation. Cox proportional hazards models, to identify associations with newly diagnosed atrial fibrillation and clinical outcomes, were stratified by country and study phase and adjusted for descriptive characteristics and comorbidities. Of 17,513 randomly sampled patients, 2188 had preexisting atrial fibrillation, with wide variation in prevalence across countries. Advanced age, non-black race, higher facility mean dialysate calcium, prosthetic heart valves, and valvular heart disease were associated with higher risk of new atrial fibrillation. Atrial fibrillation at study enrollment was positively associated with all-cause mortality and stroke. The CHADS2 score identified approximately equal-size groups of hemodialysis patients with atrial fibrillation with low (less than 2) and higher risk (more than 4) for subsequent strokes on a per 100 patient-year basis. Among patients with atrial fibrillation, warfarin use was associated with a significantly higher stroke risk, particularly in those over 75 years of age. Our study shows that atrial fibrillation is common and associated with elevated risk of adverse clinical outcomes, and this risk is even higher among elderly patients prescribed warfarin. The effectiveness and safety of warfarin in hemodialysis patients require additional investigation.

The mortality risk of overhydration in haemodialysis patients.

BACKGROUND: While cardiovascular events remain the primary form of mortality in haemodialysis (HD) patients, few centres are aware of the impact of the hydration status (HS). The aim of this study was to investigate how the magnitude of the prevailing overhydration influences long-term survival. METHODS: We measured the hydration status in 269 prevalent HD patients (28% diabetics, dialysis vintage = 41.2 +/- 70 months) in three European centres with a body composition monitor (BCM) that enables quantitative assessment of hydration status and body composition. The survival of these patients was ascertained after a follow-up period of 3.5 years. The cut off threshold for the definition of hyperhydration was set to 15% relative to the extracellular water (ECW), which represents an excess of ECW of approximately 2.5 l. Cox-proportional hazard models were used to compare survival according to the baseline hydration status for a set of demographic data, comorbid conditions and other predictors. RESULTS: The median hydration state (HS) before the HD treatment (DeltaHSpre) for all patients was 8.6 +/- 8.9%. The unadjusted gross annual mortality of all patients was 8.5%. The hyperhydrated subgroup (n = 58) presented DeltaHSpre = 19.9 +/- 5.3% and a gross mortality of 14.7%. The Cox adjusted hazard ratios (HRs) revealed that age (HRage = 1.05, 1/year; P < 0.001), systolic blood pressure (BPsys) (HRBPsys = 0.986 1/mmHg; P = 0.014), diabetes (HRDia = 2.766; P < 0.001), peripheral vascular disease (PVD) (HRPVD = 1.68; P = 0.045) and relative hydration status (DeltaHSpre) (HRDeltaHSpre = 2.102 P = 0.003) were the only significant predictors of mortality in our patient population. CONCLUSION: The results of our study indicate that the hydration state is an important and independent predictor of mortality in chronic HD patients secondary only to the presence of diabetes. We believe that it is essential to measure the hydration status objectively and quantitatively in order to obtain a more clearly defined assessment of the prognosis of haemodialysis patients.

Effect of membrane permeability on survival of hemodialysis patients.

The effect of high-flux hemodialysis membranes on patient survival has not been unequivocally determined. In this prospective, randomized clinical trial, we enrolled 738 incident hemodialysis patients, stratified them by serum albumin < or = 4 and >4 g/dl, and assigned them to either low-flux or high-flux membranes. We followed patients for 3 to 7.5 yr. Kaplan-Meier survival analysis showed no significant difference between high-flux and low-flux membranes, and a Cox proportional hazards model concurred. Patients with serum albumin < or = 4 g/dl had significantly higher survival rates in the high-flux group compared with the low-flux group (P = 0.032). In addition, a secondary analysis revealed that high-flux membranes may significantly improve survival of patients with diabetes. Among those with serum albumin < or = 4 g/dl, slightly different effects among patients with and without diabetes suggested a potential interaction between diabetes status and low serum albumin in the reduction of risk conferred by high-flux membranes. In summary, we did not detect a significant survival benefit with either high-flux or low-flux membranes in the population overall, but the use of high-flux membranes conferred a significant survival benefit among patients with serum albumin < or = 4 g/dl. The apparent survival benefit among patients who have diabetes and are treated with high-flux membranes requires confirmation given the post hoc nature of our analysis.

Whole-body spectroscopy (BCM) in the assessment of normovolemia in hemodialysis patients.

Whole-body impedance spectroscopy (BCM) has been validated by comparing isotope dilution methods for precisely measuring body volume compartments. Clinical assessment as well as comparison to other methods shows that BCM predicts a reliable individual dialysis target weight in kilograms, which corresponds to a physiological (normal) extracellular volume. BCM is helpful in the management of volume status and arterial hypertension in hemodialysis patients as well as in patients with chronic kidney disease. Quantified by BCM, overhydration is a powerful predictor of death in hemodialysis patients.

Towards improved cardiovascular management: the necessity of combining blood pressure and fluid overload.

BACKGROUND: Hypertension and fluid overload (FO) are well-recognized problems in the chronic kidney disease (CKD) population. While the prevalence of hypertension is well documented, little is known about the severity of FO in this population. METHODS: A new bioimpedance spectroscopy device (BCM-Body Composition Monitor) was selected that allows quantitative determination of the deviation in hydration status from normal ranges (DeltaHS). Pre-dialysis systolic blood pressure (BPsys) and DeltaHS was analysed in 500 haemodialysis patients from eight dialysis centres. A graphical tool (HRP-hydration reference plot) was devised allowing DeltaHS to be combined with measurements of BPsys enabling comparison with a matched healthy population (n = 1244). RESULTS: Nineteen percent of patients (n = 95) were found to have normal BPsys and DeltaHS in the normal range. Approximately one-third of patients (n = 133) exhibited reasonable control of BPsys and fluids (BPsys <150 mmHg and DeltaHS <2.5 L). In only 15% of patients (n = 74) was hypertension observed (BPsys >150 mmHg) with a concomitant DeltaHS >2.5 L (possible volume-dependent hypertension). In contrast, 13% of patients (n = 69) were hypertensive with DeltaHS <1.1 L (possible essential hypertension). In 10% of patients (n = 52), BPsys <140 mmHg was recorded despite DeltaHS exceeding 2.5 L. CONCLUSION: Our study illustrated the wide variability in BPsys regardless of the degree of DeltaHS. The HRP provides an invaluable tool for classifying patients in terms of BPsys and DeltaHS and the proximity of these parameters to reference ranges. This represents an important step towards more objective choice of strategies for the optimal treatment of hypertension and FO. Further studies are required to assess the prognostic and therapeutic role of the HRP.

The MPO Study: just a European HEMO Study or something very different?

Although results from observational and epidemiological studies suggested a survival benefit associated with high-flux hemodialysis, conclusive evidence from prospective randomized clinical trials has been lacking. Both the HEMO Study in the USA and the Membrane Permeability Outcome Study (MPO Study) in Europe are randomized studies investigating the effect of high- and low-flux hemodialysis on patient outcomes, even though there were some significant differences in the design of the two studies. An earlier randomized clinical trial could not show differences on patient survival between patient groups being treated with membranes of different material and permeability, but this trial was not designed specifically to examine this particular endpoint. Based on these previous experiences, the MPO Study addressed a hemodialysis patient population which was considered to be more susceptible to the intervention with high-flux dialysis. To identify these patients with an elevated risk, low serum albumin levels were chosen as an indicator; low serum albumin is associated with malnutrition, inflammation, atherosclerosis, and with increased risk of morbidity and mortality. Together with low serum albumin, patients had to be new to dialysis to be selected for the MPO Study. These particular considerations on patient selection, together with additional methodological refinements in the study design allow the conclusion that the MPO Study is valid on its own rather than being a European version of the HEMO Study.

Comparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatment.

OBJECTIVE: To evaluate the therapeutic efficacy and safety of epoetin zeta, compared with epoetin alfa, in maintaining target haemoglobin (Hb) concentrations in patients with anaemia and chronic kidney disease (CKD) maintained on haemodialysis. METHODS: Patients received epoetin zeta or epoetin alfa intravenously, 1-3 times/week for 12 weeks, then the alternative treatment for 12 weeks, in this double-blind, crossover, phase III trial. Eligible patients were 18-75 years old with CKD stage 5 maintained on haemodialysis. Patients had received epoetin for > or = 3 months upon study entry and had achieved a target Hb level of 10.5-12.5 g/dL with a stable epoetin dose. MAIN OUTCOME MEASURES: Primary efficacy endpoints were intra-individual differences (test-reference) in mean Hb levels and mean weekly dose/kg of body weight. Safety endpoints included occurrence of neutralizing anti-erythro poietin antibodies, tolerability, and adverse events (AEs). RESULTS: In total, 313 patients were randomized to receive epoetin zeta (n = 155) or epoetin alfa (n = 158); 146 and 145 patients (respectively) switched treatment after 12 weeks. Mean (range) Hb levels were 11.35 (8.96-14.22) g/dL and 11.54 (8.74-13.84) g/dL for patients receiving epoetin zeta and epoetin alfa, respectively (95% confidence interval [CI] [test-reference]: 0.09-0.28 g/dL, within the predefined equivalence range of +/-0.6 g/dL). Mean (range) weekly doses were 92.68 (12.74-398.41) IU/kg/wk and 92.58 (10.53-393.07) IU/kg/wk for patients receiving epoetin zeta and epoetin alfa, respectively (95% CI [test-reference]: -4.67 and 4.29 IU/kg/wk, within the equivalence range of +/-45.00 IU/kg/wk). Patients underwent minor nominal dose adjustments during treatment crossover. AE profile was similar for both products; the most commonly reported AEs were infections and infestations (in 26.5% of patients receiving epoetin zeta and 23.6% receiving epoetin alfa). No patients developed neutralizing anti-erythropoietin antibodies. CONCLUSIONS: Epoetin zeta is therapeutically equivalent to epoetin alfa in the maintenance of target Hb levels in patients with renal anaemia. No unexpected AEs were seen.

Low- (classical) and high-efficiency haemodiafiltration.

The distinction between high-efficiency haemodiafiltration (HDF), usually applied with online preparation of substitution fluid, and 'classic' low-efficiency HDF (using less than 15 litres of substitution fluid) makes sense since the magnitude of convection (expressed by substitution volume) is important for the claimed benefits of HDF. Many experimental and observational data support the notion that in comparison to conventional low-flux haemodialysis, high-efficiency HDF might have many clinical advantages and might prolong life. Randomized prospective trials, such as a current Dutch trial, are overdue to prove these hypotheses. Low-efficiency HDF is as effective as high-flux haemodialysis in providing convection. Clinical comparisons between high-flux haemodialysis and HDF are sparse. The magnitude of convection is indirectly dependent on the degree of extracorporeal blood flow. With 14-gauge needles, blood flows of >500 ml/min can be safely maintained without haemodynamic or hyperkalaemic consequences. With regard to blood purification kinetics, high-efficiency HDF appears ideal for performing daily short treatments.

Diuretic use, residual renal function, and mortality among hemodialysis patients in the Dialysis Outcomes and Practice Pattern Study (DOPPS).

BACKGROUND: Information about residual renal function (RRF) and outcomes associated with practices of diuretic use in patients with end-stage renal disease is not available worldwide. METHODS: Diuretic use was investigated in 16,420 hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study, a prospective observational study of hemodialysis patients selected from nationally representative facilities on 3 continents. Logistic regressions were used to investigate associations between diuretic use and patient characteristics. Outcomes of interdialytic weight gain, increased serum potassium and phosphorus levels, and odds of retaining RRF after 1 year were investigated. Cox regression was used to analyze the association between mortality and diuretic use. RESULTS: Facility diuretic use varied substantially from 0% to 83.9% of patients. Diuretic use decreased sharply after the start of dialysis therapy. Loop diuretic use ranged from 9.2% in the United States to 21.3% in Europe, whereas use within 90 days of starting dialysis therapy ranged from 25.0% in the United States to 47.6% in Japan. Diuretic use was associated with lower interdialytic weight gain and lower odds of hyperkalemia (potassium > 6.0 mmol/L). Patients with RRF on diuretic therapy had almost twice the odds of retaining RRF after 1 year in the study versus patients not on diuretic therapy. Patients administered diuretics had a 7% lower all-cause mortality risk (P = 0.12) and 14% lower cardiac-specific mortality risk (P = 0.03) versus patients not administered diuretics. CONCLUSION: Variation exists in facility practices of diuretic use. In patients with RRF, there may be benefit associated with continuing diuretic use rather than automatically discontinuing diuretic therapy at dialysis initiation.

Dialysis Outcomes and Practice Patterns Study (DOPPS) data on medications in hemodialysis patients.

BACKGROUND: Medications affect many measures of hemodialysis patients' well-being. METHODS: The Dialysis Outcomes and Practice Patterns Study (DOPPS) has evaluated the use of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins), analgesics, antidepressants, and multivitamins. Additionally, DOPPS has reported on the associations between vascular access outcomes and related medications. RESULTS: Prescription of statins varied widely across countries, with the highest use in the United States. Patients prescribed statins had lower risk of cardiac and noncardiac causes of mortality than those who were not prescribed statins. DOPPS data also show that statins are underprescribed relative to recent Kidney Disease Outcomes Quality Initiative guidelines. No guidelines have been established for analgesic use, but high pain levels self-reported by hemodialysis patients suggest opportunities for improved pain management strategies. Guidelines for analgesic use in dialysis patients may help balance improved quality of life against potential side effects of analgesics. Medical and patient questionnaires show that depression in hemodialysis patients is common, frequently underdiagnosed, usually untreated, and associated with increased rates of mortality and hospitalization. Calcium channel blockers were associated with improved primary graft patency, aspirin with improved secondary graft patency, and angiotensin-converting enzyme inhibitors with improved secondary fistula patency. All 3 medications were associated with significantly decreased relative risk for access failure. There is large country variation in multivitamin use, with significantly higher use in the United States compared with Europe and Japan. Patients taking multivitamins had lower mortality risk than patients not taking multivitamins. CONCLUSION: DOPPS findings on medications indicate that prospective trials are needed before guidelines can be developed for appropriate medication use in these different therapeutic categories.

Thoracic impedance measurements during orthostatic change test and during hemodialysis in hemodialyzed patients.

Measurements were performed before and after hemodialysis (HD) in the supine and upright positions (orthostatic change test) and during HD session every 30 minutes in recumbent position on 11 HD patients. Two hydration states were compared: hyperhydration and normal hydration. Each patient served as his own control. Blood pressure and total body bioimpedance were obtained simultaneously. Thoracic impedance values (Zo) obtained during HD were significantly greater in the normal hydration state. There was strong correlation between Zo gain and total ultrafiltration; however, Zo gain divided through total ultrafiltration (calculated for every 100 ml) was also higher in this state. The ratio Zo/R (where R is resistance of total body bioimpedance) was stable during HD but was significantly higher in the normal hydration state. Zo gain during the orthostatic change test was significantly higher after HD than before HD in both hydration states. The anticipated difference in Zo gains between both hydration states was not significant. After echocardiographic analysis of patients, we determined that cardiac dysfunction or valvular defects in four patients were likely responsible for opposite reaction on orthostatic change test. During our measurements, we observed the influence of Zo changes on episodes such as intradialytic hypotension or acute atrial fibrillation. Thoracic impedance is an intriguing method for controlling pathophysiology of fluid distribution, but it requires the accurate definition of a patient's hemodynamics and strong conditions during measurement. During our measurements, we observed the influence of such episodes as intradialytic hypotension or acute atrial fibrillation on Zo changes.