Constantijn Konings

Inflammation, overhydration and cardiac biomarkers in haemodialysis patients: a longitudinal study

BACKGROUND Inflammation, overhydration and elevated cardiac biomarkers are related to outcome in haemodialysis (HD) patients. Here, we explored the relationship between the body composition (BC), inflammation and cardiac biomarker concentrations in HD patients longitudinally. METHODS A total of 44 HD patients were followed for 6 months. BC was assessed by multifrequency bioimpedance (BIA). Serum concentrations of cardiac troponin T (cTnT), high-sensitive C-reactive protein (hsCRP), brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) were assessed at 2 monthly intervals. The longitudinal data analysis was conducted with a marginal model. RESULTS During the follow-up, the parameters describing the BC were highly predictive of both BNP and NT-proBNP and independent of gender, time, hsCRP and cTnT concentrations. The intracellular water (ICW)/body weight (BW) ratio (reflecting malnutrition) exerted a negative effect, whereas the extracellular water (ECW)/BW ratio (reflecting overhydration) had a positive effect on BNP and NT-proBNP concentrations. HsCRP and cTnT concentrations were significantly associated with each other. Furthermore, NT-proBNP concentrations were predictive of cTnT and hsCRP concentrations. CONCLUSIONS In the present study, we find a significant relation between BIA-derived BC parameters and natriuretic peptide concentrations. This relationship was independent of the cardiac history of the patient and suggests that the natriuretic peptide levels are to some degree modifiable by changing a patients fluid distribution. Moreover, cTnT, BNP, NT-proBNP and hsCRP were significantly related, showing a complex relation between overhydration, malnutrition, inflammation and cardiac biomarkers in dialysis patients.

Reference Values for Multifrequency Bioimpedance Analysis in Dialysis Patients

Background: The role of multifrequency bioimpedance (MF-BIA) in the assessment of fluid status in dialysis patients is still not fully elucidated. Especially, the predictive value of reference values for extracellular water (ECW) has not yet been addressed. Aim of the present study was to validate cut-off values for MF-BIA in the diagnosis of hypervolemia in dialysis patients, using strict clinical criteria and echocardiography as reference techniques. Methods: 90 patients [42 on hemodialysis; 48 on peritoneal dialysis] were divided into the following groups: clinically normovolemic (mean 24- or 48-hour systolic blood pressure below 133 mm Hg without use of antihypertensive agents; n = 12), ‘hypervolemic’ (mean systolic blood pressure above 133 mm Hg with 2 or more antihypertensive agents; n = 34) or undetermined (n = 44). The 80th percentile for normalized ECW in the clinically normovolemic patients was used as reference value. 20 healthy age-matched controls were included for comparison. Results: The 80th percentiles for ECW:body weight (BW) and ECW:height in ‘normovolemic’ subjects were, respectively, 0.245 liters/kg and 10.96 liters/m in males, and 0.232 liters/kg and 9.13 liters/m in females. ECW:BW and ECW:height were above these values in, respectively, 26 (sensitivity 76%) and 29 (sensitivity 86%) of the 34 ‘hypervolemic’ patients. In the undetermined group, left ventricular end-diastolic diameter was significantly different between patients with normalized ECW below and above these cut-off values (49.0 ± 5.1 vs. 52.4 ± 5.7 mm; p < 0.05). Use of the ECW:TBW ratio resulted yielded low sensitivity (45%). ECW:height was lower in the ‘normovolemic’ dialysis patients compared to healthy controls (9.7 ± 1.3 l/m versus 12.2 ± 1.9 l/m). Conclusion: In our study population, ECW by MF-BIA, normalized for height was able to predict hypervolemia, based on strict clinical criteria, with a sensitivity of 86% and a specificity of 80%. The normalization procedure for ECW may influence the classification of hydration status. Strictly normotensive dialysis patients had lower normalized ECW than healthy control subjects.

Peritoneal Dialysis in Patients with Primary Cardiac Failure Complicated by Renal Failure

Background/Aims: Clinical outcome in cardiorenal syndrome type II and treated with peritoneal dialysis (PD). Methods: Retrospective analysis over a period of 10 years. Results: Twenty-four patients with mean age at start of dialysis of 67 ± 10 years had mean survival on dialysis of 1.03 ± 0.84 years (median survival 1.0 year). The number of hospitalizations for cardiovascular causes were reduced (13.7 ± 26.5 predialysis vs. 3.5 ± 8.8 days/patient/month postdialysis, p = 0.001). Patients who survived longer than the median survival time (n = 12) also had a reduced number of hospitalizations for all causes (3.7 ± 3.8 predialysis vs. 1.4 ± 2.1 days/patient/month postdialysis, p = 0.041), a lower age (62 ± 10 vs. 71 ± 8 years, p = 0.013) and fewer had diabetes (2 vs. 7 patients, p = 0.039), but left ventricular ejection fraction was not different. Conclusion: After starting PD for cardiorenal syndrome, hospitalizations for cardiovascular causes were reduced for all patients. Survival after starting PD is highly variable. Age and diabetes seem to be significant prognostic factors, but not left ventricular ejection fraction.

Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

Prospective study on clinical effects of renal replacement therapy in treatment-resistant congestive heart failure

BACKGROUND/AIMS Clinical outcome in cardiorenal syndrome (CRS) Type 2 and treatment with dialysis. METHODS Prospective observational non-randomized study. RESULTS Twenty-three patients were included, mean age 66±21 years. Twelve (52%) patients were treated with peritoneal dialysis (PD) and 11 (48%) with intermittent haemodialysis (IHD). Median survival time after start of dialysis was 16 months. Hospitalizations for cardiovascular causes were reduced (1.4±0.6 pre-dialysis versus 0.4±0.6 days/patient/month post-dialysis, P=0.000), without significant changes in hospitalization for all causes (1.8±1.6 versus 2.1±2.9 days/patient/month). New York Heart Association (NYHA) class (3.8±0.4 at start versus 2.4±0.7 after 4 months, P=0.000, versus 2.7±0.9 after 8 months, P=0.001) and quality of life tended to improve (63±21 at start, versus 41±20 after 4 months, versus 51±25 after 8 months; P=0.056). Left ventricular ejection fraction did not change. The number of technical complications associated with dialysis therapy was relatively high in this population. CONCLUSIONS After starting dialysis for CRS, hospitalizations for cardiovascular causes were reduced, but not hospitalizations for all causes. Functional NYHA class improved and quality of life tended to improve, without evidence for a change in cardiac function. In this small study, no differences between IHD and PD were observed.

Fluid State and Blood Pressure Control: No Differences Between APD and CAPD

The aim of this study was to compare fluid state, ambulatory blood pressure, and sodiumremoval in automated peritoneal dialysis (APD) and continuous ambulatory peritonealdialysis (CAPD). This observational, cross-sectional study comprised 20 APD and 24 CAPD patients with a mean duration on peritoneal dialysis of 30±26 and 21 ±23 months, respectively. Sixty-four percent of the patients were treated with icodextrin. The methods used were 24 hr dialysate and urine collections, standardized 3.86% glucose peritoneal equilibration test (PET), bioimpedance analysis, and 24 hr ambulatory blood pressure monitoring. Extracellular water (ECW) corrected for body weight was 0.23 6 0.03 L/kg both in APD and CAPD patients. The slope normovolemia value according to Chamney was 0.0 6 0.2 L/kg in APD patients and 0.0 6 0.05 L/kg in CAPD patients (not significant [NS]). Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were respectively, 132 ± 25 and 79 ± 8 mm Hg in APD and 129 ± 16 and 76 ± 11 mm Hg in CAPD patients (NS). Sodium concentration in dialysate was respectively, 129.5 ± 3.5 mmol/L in APD and 132.4 ± 4.1 mmol/L in CAPD (p= 0.017). Dialysate sodium removal was 80.6 ± 78.4 mmol/24 hr in APD and 108.7 ± 96.8 mmol/24 hr in CAPD patients (NS). Natriuresis was respectively, in APD 76.6 ± 65.5 mmol/24 hr and in CAPD 93.5 ± 61.7 mmol/24 hr (NS). Total sodium removal was 149.5 ± 76.6 mmol/24 hr in APD and 198.4 ± 75.0 mmol/24 hr in CAPD (p= .039). Despite a higher daily sodium removal in CAPD patients, fluid state and blood pressure were not different between APD and CAPD. In general, volume status and blood pressure appeared to be reasonably controlled in this unselected population.

Determinants of Arterial Distensibility in Patients with Renal Failure

Background: An increased stiffness of the arterial system is an adverse risk factor for the outcome in patients with renal disease. Few studies have focused on the determinants of an increased arterial stiffness in patients with renal failure. As the percentage of patients with renal failure secondary to vascular disease and/or diabetes mellitus is rapidly growing, and the underlying disease per se may also influence the arterial wall properties, it may also be of interest to study the arterial wall properties in relation to the etiology of kidney disease. Methods: The distensibility coefficient (DC) of the common carotid artery was used as a marker of arterial stiffness. One hundred and seventeen patients were studied: 47 patients (aged 63 ± 10 years) with renal failure secondary to vascular disease and/or diabetes mellitus and 70 patients (aged 57 ± 13 years) with other diagnoses. The origin of the renal failure was retrieved from the patients’ charts. Results: Age, mean arterial pressure, and serum calcium level were each independent predictors of arterial stiffness (DC). The DC was significantly lower in the patients with vascular renal disease or diabetes mellitus [11.0 ± 5.5 (1/MPa)] as compared with patients with renal/urological diseases [15.4 ± 7.5 (1/MPa)]. Nevertheless, after correction for potentially confounding variables, the relation between cause of renal disease and DC lost significance in the overall group, but remained significant (p < 0.05) in the younger age groups (≤61 years; median age of the patient group). Conclusions: Age, mean arterial pressure, and serum calcium level were independent predictors of arterial stiffness in our patients with renal failure. Only in younger dialysis patients, the origin of renal failure was an independent predictor of arterial wall stiffness.

Low-Sodium Versus Standard-Sodium Peritoneal Dialysis Solution in Hypertensive Patients: A Randomized Controlled Trial

BACKGROUND Peritoneal dialysis (PD) solutions with reduced sodium content may have advantages for hypertensive patients; however, they have lower osmolarity and solvent drag, so the achieved Kt/Vurea may be lower. Furthermore, the increased transperitoneal membrane sodium gradient can influence sodium balance with consequences for blood pressure (BP) control. STUDY DESIGN Prospective, randomized, double-blind clinical trial to prove the noninferiority of total weekly Kt/Vurea with low-sodium versus standard-sodium PD solution, with the lower confidence limit above the clinically accepted difference of -0.5. SETTING & PARTICIPANTS Hypertensive patients (≥ 1 antihypertensive drug, including diuretics, or office systolic BP ≥ 130 mmHg) on continuous ambulatory PD therapy from 17 sites. INTERVENTION 108 patients were randomly assigned (1:1) to 6-month treatments with either low-sodium (125 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 338-491 mOsm/L) or standard-sodium (134 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 356-509 mOsm/L) PD solution. OUTCOMES Primary end point: weekly total Kt/Vurea; secondary outcomes: BP control, safety, and tolerability. MEASUREMENTS Total Kt/Vurea was determined from 24-hour dialysate and urine collection; BP, by office measurement. RESULTS Total Kt/Vurea after 12 weeks was 2.53 ± 0.89 in the low-sodium group (n = 40) and 2.97 ± 1.58 in the control group (n = 42). The noninferiority of total Kt/Vurea could not be confirmed. There was no difference for peritoneal Kt/Vurea (1.70 ± 0.38 with low sodium, 1.77 ± 0.44 with standard sodium), but there was a difference in renal Kt/Vurea (0.83 ± 0.80 with low sodium, 1.20 ± 1.54 with standard sodium). Mean daily sodium removal with dialysate at week 12 was 1.188 g higher in the low-sodium group (P < 0.001). BP changed marginally with standard-sodium solution, but decreased with low-sodium PD solution, resulting in less antihypertensive medication. LIMITATIONS Broader variability of study population than anticipated, particularly regarding residual kidney function. CONCLUSIONS The noninferiority of the low-sodium PD solution for total Kt/Vurea could not be proved; however, it showed beneficial clinical effects on sodium removal and BP.

Is there a competition between urine volume and peritoneal ultrafiltration in peritoneal dialysis patients

Many peritoneal dialysis patients are overhydrated. Overhydration may lead to hypertension and left ventricular hypertrophy, and may be related to inflammation and malnutrition. The presence of overhydration is not always detected by clinical examination. Especially patients with peritoneal ultrafiltration failure and/or negligible residual renal function are prone to overhydration. Treatment consists of a combination of sodium and fluid restriction, in combination with increased peritoneal ultrafiltration and loop diuretics in patients with residual diuresis. Peritoneal ultrafiltration can be enhanced by the use of hypertonic glucose solutions or icodextrin. In some, but not all, studies, residual renal function or diuresis declined with an increase in peritoneal ultrafiltration. At least in a subset of patients, underhydration might have played a role in this phenomenon. We propose to treat overhydration using both clinical criteria and objective techniques such as vena cava echography or bioimpedance measurements.

High-Flux Hemodialysis and High-Volume Hemodiafiltration Improve Serum Calcification Propensity

Background Calciprotein particles (CPPs) may play an important role in the calcification process. The calcification propensity of serum (T50) is highly predictive of all-cause mortality in chronic kidney disease patients. Whether T50 is therapeutically improvable, by high-flux hemodialysis (HD) or hemodiafiltration (HDF), has not been studied yet. Methods We designed a cross-sectional single center study, and included stable prevalent in-center dialysis patients on HD or HDF. Patients were divided into two groups based on dialysis modality, were on a thrice-weekly schedule, had a dialysis vintage of > 3 months and vascular access providing a blood flow rate > 300 ml/min. Calcification propensity of serum was measured by the time of transformation from primary to secondary CPP (T50 test), by time-resolved nephelometry. Results We included 64 patients, mean convective volume was 21.7L (SD 3.3L). In the pooled analysis, T50 levels increased in both the HD and HDF group with pre- and post-dialysis (mean (SD)) of 244(64) - 301(57) and 253(55) - 304(61) min respectively (P = 0.43(HD vs. HDF)). The mean increase in T50 was 26.29% for HD and 21.97% for HDF patients (P = 0.61 (HD vs. HDF)). The delta values (Δ) of calcium, phosphate and serum albumin were equal in both groups. Baseline T50 was negatively correlated with phosphate, and positively correlated with serum magnesium and fetuin-A. The ΔT50 was mostly influenced by Δ phosphate (r = -0.342; P = 0.002 HD and r = -0.396; P<0.001 HDF) in both groups. Conclusions HD and HDF patients present with same baseline T50 calcification propensity values pre-dialysis. Calcification propensity is significantly improved during both HD and HDF sessions without significant differences between both modalities.