Controversies and problems of volume control and hypertension in haemodialysis.

Extracellular volume overload and hypertension are important contributors to the high risk of cardiovascular mortality in patients undergoing haemodialysis. Hypertension is present in more than 90% of patients at the initiation of haemodialysis and persists in more than two-thirds, despite use of several antihypertensive medications. High blood pressure is a risk factor for the development of left ventricular hypertrophy, heart failure, and mortality, although there are controversies with some study findings showing poor survival with low-but not high-blood pressure. The most frequent cause of hypertension in patients undergoing haemodialysis is volume overload, which is associated with poor cardiovascular outcomes itself independent of blood pressure. Although antihypertensive medications might not be successful to control blood pressure, extracellular volume reduction by persistent ultrafiltration and dietary salt restriction can produce favourable results with good blood pressure control. More frequent or longer haemodialysis can facilitate volume and blood pressure control. However, successful volume and blood pressure control is also possible in patients undergoing conventional haemodialysis.

Interplay of volume, blood pressure, organ ischemia, residual renal function, and diet: certainties and uncertainties with dialytic management.

Extracellular fluid volume overload and its inevitable consequence, hypertension, increases cardiovascular mortality in the long term by leading to left ventricular hypertrophy, heart failure, and ischemic heart disease in dialysis patients. Unlike antihypertensive medications, a strict volume control strategy provides optimal blood pressure control without need for antihypertensive drugs. However, utilization of this strategy has remained limited because of several factors, including the absence of a gold standard method to assess volume status, difficulties in reducing extracellular fluid volume, and safety concerns associated with reduction of extracellular volume. These include intradialytic hypotension; ischemia of heart, brain, and gut; loss of residual renal function; and vascular access thrombosis. Comprehensibly, physicians are hesitant to follow strict volume control policy because of these safety concerns. Current data, however, suggest that a high ultrafiltration rate rather than the reduction in excess volume is related to these complications. Restriction of dietary salt intake, increased frequency, and/or duration of hemodialysis sessions or addition of temporary extra sessions during the process of gradually reducing postdialysis body weight in conventional hemodialysis and discontinuation of antihypertensive medications may prevent these complications. We believe that even if an unwanted effect occurs while gradually reaching euvolemia, this is likely to be counterbalanced by favorable cardiovascular outcomes such as regression of left ventricular hypertrophy, prevention of heart failure, and, ultimately, cardiovascular mortality as a result of the eventual achievement of normal extracellular fluid volume and blood pressure over the long term.

Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis.

Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

Recurrent lupus nephritis after transplantation: Clinicopathological evaluation with protocol biopsies.

AIM: Lupus nephritis (LN) is an important complication of systemic lupus erythematosus (SLE). The aim is to use indication and protocol biopsies to determine clinicopathological findings and outcomes of patients with LN undergoing kidney transplantation (KTx). METHODS: Patients who underwent KTx due to LN were retrospectively analyzed. Recurrent LN (RLN) was diagnosed by transplant kidney biopsy. RESULTS: Among 955 KTx patients, 12 patients with LN as the cause of end-stage renal disease were enrolled. Five patients were male. Mean follow-up time was 63 ± 34 months. At the last follow-up visit, mean levels of serum creatinine and proteinuria were 137.0 ± 69.0 µmol/L and 0.26 ± 0.26 g/day, respectively. Eighteen indication and 22 protocol biopsies were performed; 27 biopsies were additionally evaluated by immunofluorescence. In two recipients, subclinical RLN was confirmed by protocol biopsies. Clinical recurrence occurred in four patients. Among patients with RLN, time from diagnosis of LN to KTx was significantly shorter and use of ATG as induction treatment was significantly lower. Graft loss occurred in two recipients who had clinical RLN. Five-year overall graft survival was 85.7%. CONCLUSION: Kidney transplantation is a reasonable option for patients with ESRD secondary to SLE. However, recurrence of LN is common if protocol biopsies are included in post-transplantation surveillance.

Long-term outcome of kidney transplantation from elderly living and expanded criteria deceased donors.

The imbalance between organ demand and supply causes the increasing use of suboptimal donors. The aim of this study is to investigate the survival and allograft function of kidney transplantation from standard (SLD) and elderly living (ELD), standard criteria (SCDD) and expanded criteria deceased (ECDD) donors. All patients transplanted from 1997 to 2005 were investigated according to the donor characteristics. Data were collected retrospectively during the 83.4±43.1 months of follow-up period. ELD was defined as donor age≥60 years. ECDD was defined as UNOS criteria. A total of 458 patients were divided into four groups: SLD (n:191), ELD (n:67), SCDD (n:154), and ECDD (n:46). Seven-year death-censored graft survival in SLD, ELD, SCDD, and ECDD were 81.6%, 64.8%, 84.7%, and 68.3%, respectively (p=0.003). The death-censored graft survival in ELD group was lower than in SLD (p=0.007) and SCDD (p=0.007) groups, while in ECDD group it was lower than in SCDD group (p=0.026). Patient survival was similar. In ECDD group, 83% of total deaths occurred within the first 3 years, mainly due to infections (66.6%) (p<0.05). Estimated glomerular filtration rate (eGFR) was lower in ELD (compared with SLD and SCDD); and ECDD (compared with SCDD) at last visit. In multivariate analysis, ELD, experience of an acute rejection episode and presence of delayed graft function were the independent predictors for death censored graft loss. Transplantation of a suboptimal kidney provides inferior graft survival and function. A higher number of deaths due to infection in the early post-transplant period in the ECDD group are noteworthy.

Glycated hemoglobin predicts overall and cardiovascular mortality in non-diabetic hemodialysis patients.

AIMS: Besides diabetic patients, glycated hemoglobin (HbA1c) levels have been reported to predict mortality in non-diabetics patients. However, the importance of HbA1c levels in non-diabetic hemodialysis patients still remains unknown. Thus, we aimed to prospectively investigate the impact of HbA1c on all-cause and cardiovascular mortality in a large group of prevalent non-diabetic hemodialysis patients. METHODS: HbA1c was measured quarterly in 489 non-diabetic prevalent hemodialysis patients. Overall and cardiovascular mortality were evaluated over a 3 year follow-up. RESULTS: Mean HbA1c level was 4.88 ± 0.46% (3.5 - 6.9%). During the 28.3 ± 10.6 months follow-up period, 67 patients (13.7%) died; 31 from cardiovascular causes. In Kaplan-Meier analysis, patients in the lowest (< 4.69%) and highest HbA1c (> 5.04%) tertiles had poorer overall survival compared to the middle HbA1c tertile (p < 0.001). Adjusted Cox-regression analysis revealed that the highest HbA1c tertile was associated with both overall (HR = 3.60, 95% CI 1.57 - 8.27, p = 0.002) and cardiovascular (HR = 6.66, 95% CI 1.51 - 29.4; p = 0.01) mortality. Also, low HbA1c levels tended to be associated with overall mortality (HR = 2.26, 95% CI 0.96 - 5.29, p = 0.06). CONCLUSION: Upper normal HbA1c levels are independently associated with cardiovascular and overall mortality in non-diabetic hemodialysis patients, whereas lower HbA1c levels are not.

The impact of membrane permeability and dialysate purity on cardiovascular outcomes.

The effects of high-flux dialysis and ultrapure dialysate on survival of hemodialysis patients are incompletely understood. We conducted a randomized controlled trial to investigate the effects of both membrane permeability and dialysate purity on cardiovascular outcomes. We randomly assigned 704 patients on three times per week hemodialysis to either high- or low-flux dialyzers and either ultrapure or standard dialysate using a two-by-two factorial design. The primary outcome was a composite of fatal and nonfatal cardiovascular events during a minimum 3 years follow-up. We did not detect statistically significant differences in the primary outcome between high- and low-flux (HR=0.73, 95% CI=0.49 to 1.08, P=0.12) and between ultrapure and standard dialysate (HR=0.90, 95% CI=0.61 to 1.32, P=0.60). Posthoc analyses suggested that cardiovascular event-free survival was significantly better in the high-flux group compared with the low-flux group for the subgroup with arteriovenous fistulas, which constituted 82% of the study population (adjusted HR=0.61, 95% CI=0.38 to 0.97, P=0.03). Furthermore, high-flux dialysis associated with a lower risk for cardiovascular events among diabetic subjects (adjusted HR=0.49, 95% CI=0.25 to 0.94, P=0.03), and ultrapure dialysate associated with a lower risk for cardiovascular events among subjects with more than 3 years of dialysis (adjusted HR=0.55, 95% CI=0.31 to 0.97, P=0.04). In conclusion, this trial did not detect a difference in cardiovascular event-free survival between flux and dialysate groups. Posthoc analyses suggest that high-flux hemodialysis may benefit patients with an arteriovenous fistula and patients with diabetes and that ultrapure dialysate may benefit patients with longer dialysis vintage.

Effects of incremental peritoneal dialysis with low glucose-degradation product neutral pH solution on clinical outcomes.

PURPOSE: Incremental peritoneal dialysis (IPD) could decrease unfavorable glucose exposure results and preserve (RKF). However, there is no standardization of dialysis prescriptions for patients undergoing IPD. We designed a prospective observational multi-center study with a standardized IPD prescription to evaluate the effect of IPD on RKF, metabolic alterations, blood pressure control, and adverse outcomes. METHODS: All patients used low GDP product (GDP) neutral pH solutions in both the incremental continuous ambulatory peritoneal dialysis (ICAPD) group and the retrospective standard PD (sPD) group. IPD patients started treatment with three daily exchanges five days a week. Control-group patients performed four changes per day, seven days a week. RESULTS: A total of 94 patients (47 IPD and 47 sPD) were included in this study. The small-solute clearance and mean blood pressures were similar between both groups during follow-up. The weekly mean glucose exposure was significantly higher in sPD group than IPD during the follow-up (p < 0.001). The patients with sPD required more phosphate-binding medications compared to the IPD group (p = 0.05). The rates of peritonitis, tunnel infection, and hospitalization frequencies were similar between groups. Patients in the sPD group experienced more episodes of hypervolemia compared to the IPD group (p = 0.007). The slope in RKF in the 6th month was significantly higher in the sPD group compared to the IPD group (65% vs. 95%, p = 0.001). CONCLUSION: IPD could be a rational dialysis method and provide non-inferior dialysis adequacy compared to full-dose PD. This regimen may contribute to preserving RKF for a longer period.

Effect of fluid management guided by bioimpedance spectroscopy on cardiovascular parameters in hemodialysis patients: a randomized controlled trial.

BACKGROUND: Fluid overload is the main determinant of hypertension and left ventricular hypertrophy in hemodialysis patients. However, assessment of fluid overload can be difficult in clinical practice. We investigated whether objective measurement of fluid overload with bioimpedance spectroscopy is helpful in optimizing fluid status. STUDY DESIGN: Prospective, randomized, and controlled study. SETTING & PARTICIPANTS: 156 hemodialysis patients from 2 centers were randomly assigned to 2 groups. INTERVENTION: Dry weight was assessed by routine clinical practice and fluid overload was assessed by bioimpedance spectroscopy in both groups. In the intervention group (n = 78), fluid overload information was provided to treating physicians and used to adjust fluid removal during dialysis. In the control group (n = 78), fluid overload information was not provided to treating physicians and fluid removal during dialysis was adjusted according to usual clinical practice. OUTCOMES: The primary outcome was regression of left ventricular mass index during a 1-year follow-up. Improvement in blood pressure and left atrial volume were the main secondary outcomes. Changes in arterial stiffness parameters were additional outcomes. MEASUREMENTS: Fluid overload was assessed twice monthly in the intervention group and every 3 months in the control group before the mid- or end-week hemodialysis session. Echocardiography, 48-hour ambulatory blood pressure measurement, and pulse wave analysis were performed at baseline and 12 months. RESULTS: Baseline fluid overload parameters in the intervention and control groups were 1.45 ± 1.11 (SD) and 1.44 ± 1.12 L, respectively (P = 0.7). Time-averaged fluid overload values significantly decreased in the intervention group (mean difference, -0.5 ± 0.8 L), but not in the control group (mean difference, 0.1 ± 1.2 L), and the mean difference between groups was -0.5 L (95% CI, -0.8 to -0.2; P = 0.001). Left ventricular mass index regressed from 131 ± 36 to 116 ± 29 g/m(2) (P < 0.001) in the intervention group, but not in the control group (121 ± 35 to 120 ± 30 g/m(2); P = 0.9); mean difference between groups was -10.2 g/m(2) (95% CI, -19.2 to -1.17 g/m(2); P = 0.04). In addition, values for left atrial volume index, blood pressure, and arterial stiffness parameters decreased in the intervention group, but not in the control group. LIMITATIONS: Ambulatory blood pressure data were not available for all patients. CONCLUSIONS: Assessment of fluid overload with bioimpedance spectroscopy provides better management of fluid status, leading to regression of left ventricular mass index, decrease in blood pressure, and improvement in arterial stiffness.

Effects of three times weekly eight-hour nocturnal hemodialysis on volume and nutritional status.

BACKGROUND: This prospective cohort study compared the changes in body water composition and nutritional parameters measured with multifrequency bioimpedance analysis between 8-hour three times weekly nocturnal hemodialysis (NHD) and 4-hour conventional hemodialysis (CHD) patients. PATIENTS AND METHODS: 55 patients on CHD and 57 patients on NHD were included in the study. Multifrequency bioimpedance analysis was performed at baseline and at the 12th month. The primary outcomes of the study were changes in extracellular water (ECW), fat mass, dry lean mass and phase angle. Secondary outcomes of the study included changes in blood pressure and biochemical parameters related to nutrition and inflammation. RESULTS: ECW/height values decreased in the NHD group, while they increased in the CHD group. Fat mass, dry lean mass, and serum albumin increased and high sensitive CRP decreased in the NHD group but did not change in the CHD group. When changes in parameters from baseline to the 12th month between the groups were compared, NHD was associated with improvement in volume parameter including ECW/height (difference -0.44 l/m, p < 0.001). Change in blood pressure was not different between the groups, however requirement for antihypertensive medication decreased from 26.5 to 8.5% in the NHD group (p = 0.002). NHD was also associated with increases in fat mass (difference 1.8 kg, p < 0.001), dry lean mass (difference 0.6 kg, p = 0.006), serum albumin (difference 0.19 g/dl, p < 0.001) and cholesterol (difference 18.8 mg, p < 0.001). Phase angle values decreased in the CHD group but did not change in the NHD group (difference between the groups 0.37°, p = 0.04). CONCLUSION: This study revealed that longer HD facilitates volume control and improves nutritional status.

Mortality and cardiovascular events in online haemodiafiltration (OL-HDF) compared with high-flux dialysis: results from the Turkish OL-HDF Study.

BACKGROUND: Online haemodiafiltration (OL-HDF) is considered to confer clinical benefits over haemodialysis (HD) in terms of solute removal in patients undergoing maintenance HD. The aim of this study was to compare postdilution OL-HDF and high-flux HD in terms of morbidity and mortality. METHODS: In this prospective, randomized, controlled trial, we enrolled 782 patients undergoing thrice-weekly HD and randomly assigned them in a 1:1 ratio to either postdilution OL-HDF or high-flux HD. The mean age of patients was 56.5 ± 13.9 years, time on HD 57.9 ± 44.6 months with a diabetes incidence of 34.7%. The follow-up period was 2 years, with the mean follow-up of 22.7 ± 10.9 months. The primary outcome was a composite of death from any cause and nonfatal cardiovascular events. The major secondary outcomes were cardiovascular and overall mortality, intradialytic complications, hospitalization rate, changes in several laboratory parameters and medications used. RESULTS: The filtration volume in OL-HDF was 17.2 ± 1.3 L. Primary outcome was not different between the groups (event-free survival of 77.6% in OL-HDF versus 74.8% in the high-flux group, P = 0.28), as well as cardiovascular and overall survival, hospitalization rate and number of hypotensive episodes. In a post hoc analysis, the subgroup of OL-HDF patients treated with a median substitution volume >17.4 L per session (high-efficiency OL-HDF, n = 195) had better cardiovascular (P = 0.002) and overall survival (P = 0.03) compared with the high-flux HD group. In adjusted Cox-regression analysis, treatment with high-efficiency OL-HDF was associated with a 46% risk reduction for overall mortality {RR = 0.54 [95% confidence interval (95% CI) 0.31-0.93], P = 0.02} and a 71% risk reduction for cardiovascular mortality [RR = 0.29 (95% CI 0.12-0.65), P = 0.003] compared with high-flux HD. CONCLUSIONS: The composite of all-cause mortality and nonfatal cardiovascular event rate was not different in the OL-HDF and in the high-flux HD groups. In a post hoc analysis, OL-HDF treatment with substitution volumes over 17.4 L was associated with better cardiovascular and overall survival.

The associations between serum paraoxonase 1 activity and carotid atherosclerosis in renal transplant patients.

BACKGROUNDS AND AIMS: Paraoxonase 1 (PON1) is a novel marker that has been shown to exert protective functions on atherosclerosis by preventing oxidative modification of serum lipoproteins. In this study, we investigated the effects of PON1 on CA-IMT in renal transplant patients. METHODS: A total of 98 adult renal transplant recipients was enrolled in the study. CA-IMT was determined by B-mode Doppler ultrasonography. PON-1 activity was assessed by the rate of enzymatic hydrolysis of paraoxon to p-nitrophenol. RESULTS: Mean age was 39.4 ± 9.6 years and 10% of the patients were diabetic. Time after transplant was 76 ± 59 months. Mean PON1 level was 62.1 ± 43.3 U/l. PON1 levels were negatively correlated with CA-IMT and positively with HDL cholesterol. Mean CA-IMT was 0.62 ± 0.10 mm (0.40 - 0.98). CA-IMT was positively correlated with age, male gender and negatively with proteinuria and PON1 levels. In linear regression analysis, PON1 levels were associated with CA-IMT. CONCLUSION: Reduced PON1 activity is significantly associated with increased carotid atherosclerosis in renal transplant patients.

The evidence of occult hypervolemia; improvement of cardiac functions after kidney transplantation.

The term cardiorenal syndrome (CRS) has been used to define interactions between acute or chronic dysfunction of the heart or kidney. When primary chronic kidney disease contribute to cardiac dysfunction, it is classified as type 4 CRS. Cardiac dilatation, valve regurgitations, and left ventricular dysfunction are observed in end-stage renal failure patients with uremic cardiomyopathy. Because of perioperative risks in these patients, they may not be considered a candidate for kidney transplantation. However, uremic cardiomyopathy can be corrected when volume control is achieved by appropriate dose and duration of ultrafiltration. By presenting two cases with occult hypervolemia in uremic cardiomyopathy whose cardiac functions improved early after kidney transplantation, attention is drawn to the importance of kidney transplantation on cardiac function in such patients primarily and the importance of strict volume control on cardiac function in dialysis patients waiting for kidney transplantation.

The impact of low serum sodium level on mortality depends on glycemic control.

BACKGROUND: Low serum sodium levels have been associated with mortality both in patients with and without chronic kidney disease. In this study, we investigated this association in relation to glycemic control in hemodialysis (HD) patients. MATERIALS AND METHODS: Between March and September 2005, 697 prevalent HD patients were enrolled in this prospective observational study and followed up for all-cause and cardiovascular mortality. The associations of serum sodium concentration with both overall and cardiovascular survival rates were studied. RESULTS: At baseline, mean predialysis serum sodium concentration was 138.4 ± 2.3 mEq/L (range: 130-145 mEq/L). Mild hyponatremia (< 135 mEq/L) was present in only 41 subjects (5.9%), and no patient had serum sodium level < 130 mEq/L. During 20.2 ± 6.2 months of follow-up, 119 patients (15.9%) died, 68 from CV causes. In adjusted Cox regression analysis, lowest sodium quartile was associated with 2.13-fold increased risk of overall mortality (95% confidence interval (CI) 1.14-3.98, P = 0.01, model chi-square 114.6, P < 0.001). As a continuous variable, each 1 mEq/L increase in predialysis sodium concentration was associated with a hazard ratio (HR) of 0.87 for overall mortality (95% CI 0.81-0.95, P = 0.002) and 0.86 for cardiovascular mortality (95% CI 0.78-0.96, P = 0.007). The predictivity of low serum sodium was prominent in diabetic subjects but not in nondiabetics. However, relationship between serum sodium and patient survival in diabetics was lost after adjustment for the HbA1c level: HR 0.91 (95% CI 0.78-1.05, P = 0.20). CONCLUSIONS: Low serum sodium concentration is associated with mortality only in those with diabetes. Furthermore, the impact of serum sodium on survival in these patients seems to be derived from poor glucose control.

Impact of mean arterial pressure on progression of arterial stiffness in peritoneal dialysis patients under strict volume control strategy.

INTRODUCTION: Arterial stiffness is an important contributor to the increased cardiovascular burden of uremia. The aim of the study was to identify determinants of arterial stiffness progression in peritoneal dialysis (PD) patients with strict volume control. PATIENTS AND METHODS: 89 prevalent PD patients were enrolled. Assessment of arterial stiffness was performed at baseline and after nine months on average (range 8 - 12 months) by carotid-femoral pulse wave velocity (cf-PWV). RESULTS: Mean age was 51 ± 13 y; preceeding time on PD was 40 ± 34 months. 57% of the patients were men and 9% were diabetic. At baseline, mean cf- PWV was 8.7 ± 2.7 m/s and was significantly higher in patients with diabetes and on automated PD therapy. Cf-PWV was positively correlated with age, history of cardiovascular disease, mean arterial pressure (MAP), blood glucose, left atrium diameter and left ventricular mass index. Sixty patients underwent a second cf-PWV measurement. 36% had progression of arterial stiffness. Delta cf- PWV value was 2.08 ± 1.89 m/s for progressors and -1.25 ± 1.43 m/s; p < 0.01 for nonprogressors (p < 0.01). In logistic regression analysis, the change in MAP was the only predictor for progression of arterial stiffness. CONCLUSIONS: MAP is the main determinant of arterial stiffness progression. Our results suggest that efficient blood pressure control may contribute to preserved or reduced arterial stiffness in PD patients.

Nutritional state alters the association between free triiodothyronine levels and mortality in hemodialysis patients.

BACKGROUND: Serum free triiodothyronine (fT3) level is suggested to be a risk factor for mortality in unselected dialysis patients. We investigated the prognostic value of serum fT3 levels and also low-T3 syndrome on overall survival in a large cohort of hemodialysis (HD) patients with normal thyroid-stimulating hormone levels. METHODS: A total of 669 prevalent HD patients were enrolled in the study. Serum fT3 level was measured by enzyme immune assay in frozen sera samples at the time of enrollment. Overall mortality was assessed during 48 months of follow-up. RESULTS: Baseline fT3 was 1.47 ± 0.43 (0.01-2.98) pg/ml, and low-T3 syndrome was present in 71.7% of the cases. During a mean follow-up of 34 ± 16 months, 165 (24.7%) patients died. fT3 level was a strong predictor for mortality in crude and adjusted Cox models including albumin or high-sensitivity C-reactive protein (hs-CRP). Further adjustment for both albumin and hs-CRP made the impact of fT3 on mortality disappear. The presence of low-T3 syndrome was associated with mortality in only the unadjusted model. CONCLUSIONS: Low-T3 syndrome is a frequent finding among HD patients, but it does not predict outcome. However, serum fT3 level is a strong and inverse mortality predictor, in part explained by its underlying association with nutritional state and inflammation.

Relations between malnutrition-inflammation-atherosclerosis and volume status. The usefulness of bioimpedance analysis in peritoneal dialysis patients.

BACKGROUND: Chronic fluid overload (FO) is frequently present in peritoneal dialysis (PD) patients and is associated with hypertension and left ventricular hypertrophy and dysfunction, which are important predictors of death in dialysis patients. In the present study, we investigated the relationship between nutrition, inflammation, atherosclerosis and body fluid volumes measured by multi-frequency bioimpedance analysis (m-BIA) in PD patients. In addition, we analysed the relationship of extracellular volume values by m-BIA to echocardiographic parameters in order to define its usefulness as a measure of FO. METHODS: Ninety-five prevalent PD patients (mean age 50 ± 13 years, 10 of them diabetic) were enrolled. Extracellular water (ECW), total body water (TBW), dry lean mass (DLM) and phase angle (PA) were measured by m-BIA. Volume status was determined by measuring left atrium diameter (LAD) and left ventricular end-diastolic diameter (LVEDD). Measurement of carotid artery intima-media thickness (CA-IMT) was used to assess the presence of subclinical atherosclerosis. Serum albumin was used as a nutritional marker, and serum C-reactive protein (CRP) was used as an inflammatory marker. RESULTS: Mean ECW/height was 10.0 ± 1.0 L/m for whole group and 9.3 ± 0.6 L/m in patients with normal clinical hydration parameters. In correlation analysis, markers of nutrition, inflammation and atherosclerosis correlated well with m-BIA parameters. When we used echographically measured LAD (> 40 mm) or LVEDD (> 55 mm) as a confirmatory parameter, a cut-off value of 10.48 L/m ECW/height (78% specificity, with a sensitivity of 77% for LAD and 72% specificity, with a sensitivity of 70% for LVEDD) was found in ROC analysis for the diagnosis of FO. Patients with FO were older and had higher systolic blood pressure, cardiothoracic index, serum CRP level and mean CA-IMT than patients without FO. Patients with inflammation had higher CA-IMT values. In multivariate analysis, only two factors-low urine output and ECW/height-were independently associated with the presence of inflammation. CONCLUSIONS: FO defined by m-BIA is significantly correlated with markers of malnutrition, inflammation and atherosclerosis in PD patients. The indices obtained from m-BIA, especially ECW/height, correlated well with volume overload as assessed by echocardiography and might be a measure worth testing in a properly designed clinical study.

The link between bone and coronary calcifications in CKD-5 patients on haemodialysis.

BACKGROUND: Vascular calcifications are frequent in Stage 5 chronic kidney disease (CKD-5) patients receiving haemodialysis. The current study was designed to evaluate the associations between bone turnover/volume and coronary artery calcifications (CAC). METHODS: In 207 CKD-5 patients, bone biopsies, multislice computed tomography of the coronary arteries and blood drawings for relevant biochemical parameters were done. The large number of CKD-5 patients enrolled allowed separate evaluation of patients with CAC versus patients without CAC and adjustment for traditional and non-traditional risk factors for CAC. RESULTS: When all patients were analysed, associations were found between CAC and bone turnover, bone volume, age, gender and dialysis vintage. When only patients with CAC were included, there was a U-shaped relationship between CAC and bone turnover, whilst the association with bone volume was lost. In these patients, the relationship of CAC with age, gender and dialysis vintage remained. CONCLUSIONS: Beyond the non-modifiable risk factors of age, gender and dialysis vintage, these data show that bone abnormalities of renal osteodystrophy amenable to treatment should be considered in the management of patients with CAC.

Comparison of 4- and 8-h dialysis sessions in thrice-weekly in-centre haemodialysis: a prospective, case-controlled study.

BACKGROUND: Longer dialysis sessions may improve outcome in haemodialysis (HD) patients. We compared the clinical and laboratory outcomes of 8- and 4-h thrice-weekly HD. METHODS: Two-hundred and forty-seven HD patients who agreed to participate in a thrice-weekly 8-h in-centre nocturnal HD (NHD) treatment and 247 age-, sex-, diabetes status- and HD duration-matched control cases to 4-h conventional HD (CHD) were enrolled in this prospective controlled study. Echocardiography and psychometric measurements were performed at baseline and at the 12th month. The primary outcome was 1-year overall mortality. RESULTS: Overall mortality rates were 1.77 (NHD) and 6.23 (CHD) per 100 patient-years (P = 0.01) during a mean 11.3 ± 4.7 months of follow-up. NHD treatment was associated with a 72% risk reduction for overall mortality compared to the CHD treatment (hazard ratio = 0.28, 95% confidence interval 0.09-0.85, P = 0.02). Hospitalization rate was lower in the NHD arm. Post-HD body weight and serum albumin levels increased in the NHD group. Use of antihypertensive medications and erythropoietin declined in the NHD group. In the NHD group, left atrium and left ventricular end-diastolic diameters decreased and left ventricular mass index regressed. Both use of phosphate binders and serum phosphate level decreased in the NHD group. Cognitive functions improved in the NHD group, and quality of life scores deteriorated in the CHD group. CONCLUSIONS: Eight-hour thrice-weekly in-centre NHD provides morbidity and possibly mortality benefits compared to conventional 4-h HD.

The impact of strict volume control strategy on patient survival and technique failure in peritoneal dialysis patients.

Strict volume control strategy provides better cardiac functions and control of hypertension in dialysis patients. We investigated the effect of this strategy on mortality and technique failure in peritoneal dialysis patients over a 10-year period. 243 patients were enrolled. Strict volume control by dietary salt restriction and ultrafiltration was applied. Mean systolic and diastolic blood pressures decreased from 138.4 ± 29.9 and 86.3 ± 16.8 to 114.9 ± 32.3 and 74.7 ± 18.3 mm Hg, respectively. Overall and cardiovascular mortality rates were 48.4 and 29.6 per 1,000 patient-years, respectively. In multivariate analysis, age, diabetes and baseline serum albumin level were independent predictors of overall mortality, and age, diabetes and baseline serum calcium of cardiovascular mortality. Residual diuresis and peritoneal equilibration test values were not related to mortality. Strict volume control leads to lower mortality than comparable series in the literature. Technique survival is better during the first 3 years, but not after 5 years.