The correlation of urea and creatinine concentrations in sweat and saliva with plasma during hemodialysis: an observational cohort study.

OBJECTIVES: Urea and creatinine concentrations in plasma are used to guide hemodialysis (HD) in patients with end-stage renal disease (ESRD). To support individualized HD treatment in a home situation, there is a clinical need for a non-invasive and continuous alternative to plasma for biomarker monitoring during and between cycles of HD. In this observational study, we therefore established the correlation of urea and creatinine concentrations between sweat, saliva and plasma in a cohort of ESRD patients on HD. METHODS: Forty HD patients were recruited at the Dialysis Department of the Catharina Hospital Eindhoven. Sweat and salivary urea and creatinine concentrations were analyzed at the start and at the end of one HD cycle and compared to the corresponding plasma concentrations. RESULTS: A decrease of urea concentrations during HD was observed in sweat, from 27.86 mmol/L to 12.60 mmol/L, and saliva, from 24.70 mmol/L to 5.64 mmol/L. Urea concentrations in sweat and saliva strongly correlated with the concentrations in plasma (ρ 0.92 [p<0.001] and 0.94 [p<0.001], respectively). Creatinine concentrations also decreased in sweat from 43.39 µmol/L to 19.69 µmol/L, and saliva, from 59.00 µmol/L to 13.70 µmol/L. However, for creatinine, correlation coefficients were lower than for urea for both sweat and saliva compared to plasma (ρ: 0.58 [p<0.001] and 0.77 [p<0.001], respectively). CONCLUSIONS: The results illustrate a proof of principle of urea measurements in sweat and saliva to monitor HD adequacy in a non-invasive and continuous manner. Biosensors enabling urea monitoring in sweat or saliva could fill in a clinical need to enable at-home HD for more patients and thereby decrease patient burden.

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.

Dynamics of Nutritional Competence in the Last Year Before Death in a Large Cohort of US Hemodialysis Patients.

OBJECTIVES: Recently, a new Nutritional Competence Score (NCS) has been shown to associate with hospitalization and outcome in hemodialysis patients. The aim of this study was to investigate the dynamics, the individual components, and the impact of hospitalizations of this score's trajectory in the year before death. In addition, we investigated whether dynamics in the NCS add additional independent prognostic value over a single cross-sectional assessment. DESIGN: We included all Fresenius Medical Care North America patients who initiated hemodialysis between January 1, 2006, and December 31, 2011 with data on all 5 NCS components (serum albumin, creatinine, phosphate, equilibrated normalized protein catabolic rate, and interdialytic weight gain) in at least 1 month. NCS was quantified monthly, and trajectories were compared between nonsurvivors and survivors across different dialysis vintage strata. Survivors and nonsurvivors were matched by dialysis vintage. The association of baseline NCS and NCS dynamics with mortality risk were assessed with Cox proportional hazards models. RESULTS: In this cohort of 110,794 patients, we found that across all vintage groups, NCS was lower in patients who died than in survivors. NCS was found to significantly decline before death, whereas survivors showed no decline in NCS. The rate of NCS decline before death was not materially influenced by hospitalization in the months before death. Cox models showed that NCS dynamics over time carry significant predictive power above a cross-sectional NCS assessment. CONCLUSIONS: There are distinct differences in NCS values and their trajectories between patients who die and vintage-matched controls. These differences may be able to be exploited for implementation of a routine, prospective monitoring tool for early detection of patients at increased risk of death. Prospective studies are required to validate such an approach.

Moderate elevations of high-sensitivity cardiac troponin I and B-type natriuretic peptide in chronic hemodialysis patients are associated with mortality.

BACKGROUND: Several biomarkers are associated with mortality in hemodialysis patients. In particular, elevated cardiac troponin T and B-type natriuretic peptide (BNP) are strong predictors of mortality; however, less is known about cardiac troponin I (cTnI). Elevated troponin I is detected in many hemodialysis patients, but the association of moderate elevations with mortality is unclear. METHODS: The relation between mortality and cTnI, using a high-sensitivity cTnI assay, as well as BNP and C-reactive protein (CRP) was evaluated in 206 chronic hemodialysis patients. RESULTS: Median follow-up was 28 months with a total mortality of 35%. Mortality was significantly associated with elevated cTnI, BNP and CRP. Even patients with only moderate elevation of cTnI (0.01-0.10 µg/L) showed 2.5-fold increased mortality. Interestingly, hazard ratios for mortality for single (random) measurements were comparable to those for mean/median measurements. Subsequently, subgroup analysis based on combined markers was performed. Patients with both cTnI <0.01 µg/L and BNP in the first quartile had 100% survival. Patients with either cTnI <0.01 µg/L or BNP in the lowest quartile had significantly lower mortality (12% and 13%, respectively) than patients with BNP levels in the second quartile or higher and cTnI of 0.01-0.05 µg/L and patients with cTnI ≥0.05 µg/L (mortality 46 and 58%, respectively). CONCLUSIONS: A combination of moderate elevation of cTnI and BNP provided additional prognostic value. A single measurement of these biomarkers performed comparably to the mean/median of multiple measurements.

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.

Effect of citric-acid dialysate on the QTC-interval.

Lower dialysate calcium (dCa) concentration and dialysate citric-acidification may positively affect calcification propensity in serum of haemodialysis (HD) patients. However, the accompanying lower ionized blood calcium concentration may lead to a prolonged cardiac action potential, which is possibly pro-arrhythmic. The aim of this study is to investigate the influence of citric-acid dialysate on the QT-interval corrected for heart rate (QTc) compared to conventional dialysate with different dCa concentrations. We conducted a four-week multicentre, randomized cross-over trial. In week one and three patients received acetic-acid dialysate with a dCa of 1.50 mmol/l (A1.5), in week two and four acetic-acid dialysate with a dCa of 1.25 mmol/l (A1.25) or citric-acid dialysate (1.0 mmol/l) with a dCa of 1.50 mmol/l (C1.5) depending on randomization. Patients had continuous ECG monitoring during one session in week one, two and four. The data of 13 patients were available for analysis. Results showed a significant though limited increase of QTc with C1.5 (from 427 to 444 ms (start to end); p = 0.007) and with A1.25 (from 431 to 449 ms; p < 0.001), but not with A1.5 (from 439 to 443 ms; p = 0.13). In conclusion, we found that the use of C1.5 or A1.25 is associated with a significant prolongation of QTc which was however relatively limited.

Changes in pre-dialysis blood pressure variability in the first year of dialysis associate with mortality in European hemodialysis patients: a retrospective cohort study on behalf of the MONDO Initiative.

Pre-hemodialysis systolic blood pressure variability (pre-HD SBPV) has been associated with outcomes. The association of a change in pre-HD SBPV over time with outcomes, and predictors of this change, has not yet been studied. Therefore, we studied this in a cohort of 8825 incident hemodialysis (HD) patients from the European Monitoring Dialysis Outcomes Initiative database. Patient level pre-HD SBPV was calculated as the standard deviation of the residuals of a linear regression model of systolic blood pressure (SBP) over time divided by individual mean SBP in the respective time periods. The pre-HD SBPV difference between months 1-6 and 7-12 was used as an indicator of pre-HD SBPV change. The association between pre-HD SBPV change and all-cause mortality in year 2 was analyzed by multivariate Cox models. Predictors of pre-HD SBPV change was determined by logistic regression models. We found the highest pre-HD SBPV tertile, in the first 6 months after initiation of HD, had the highest mortality rates (adjusted HR 1.44 (95% confidence intervals (95% CI): 1.15-1.79)). An increase in pre-HD SBPV between months 1-6 and 7-12 was associated with an increased risk of mortality in year 2 (adjusted HR 1.29 (95% CI: 1.05-1.58)) compared with stable pre-HD SPBV. A pre-HD SBPV increase was associated with female gender, higher mean pre-HD SBP and pulse pressure, and lower HD frequency.

Advanced glycation endproducts and dicarbonyls in end-stage renal disease: associations with uraemia and courses following renal replacement therapy.

BACKGROUND: End-stage renal disease (ESRD) is strongly associated with cardiovascular disease (CVD) risk. Advanced glycation endproducts (AGEs) and dicarbonyls, major precursors of AGEs, may contribute to the pathophysiology of CVD in ESRD. However, detailed data on the courses of AGEs and dicarbonyls during the transition of ESRD patients to renal replacement therapy are lacking. METHODS: We quantified an extensive panel of free and protein-bound serum AGEs [N ∈-(carboxymethyl)lysine (CML), N ∈-(carboxyethyl)lysine (CEL), N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)], serum dicarbonyls [glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG)] and tissue AGE accumulation [estimated by skin autofluorescence (SAF)] in a combined cross-sectional and longitudinal observational study of patients with ESRD transitioning to dialysis or kidney transplantation (KTx), prevalent dialysis patients and healthy controls. Cross-sectional comparisons were performed with linear regression analyses, and courses following renal replacement therapy were analysed with linear mixed models. RESULTS: Free and protein-bound AGEs, dicarbonyls and SAF were higher in chronic kidney disease (CKD) Stage 5 non-dialysis (CKD 5-ND; n = 52) and CKD Stage 5 dialysis (CKD 5-D; n = 35) than in controls (n = 42). In addition, free AGEs, protein-bound CML, GO and SAF were even higher in CKD 5-D than in CKD5-ND. Similarly, following dialysis initiation (n = 43) free and protein-bound AGEs, and GO increased, whereas SAF remained similar. In contrast, following KTx (n = 21), free and protein-bound AGEs and dicarbonyls, but not SAF, markedly declined. CONCLUSIONS: AGEs and dicarbonyls accumulate in uraemia, which is even exaggerated by dialysis initiation. In contrast, KTx markedly reduces AGEs and dicarbonyls. Given their associations with CVD risk in high-risk populations, lowering AGE and dicarbonyl levels may be valuable.

Quantification of free water transport during the peritoneal equilibration test.

OBJECTIVE: Free water transport (FWT) can be calculated after a dwell of 1 hour with a 3.86% glucose solution using sodium kinetics (mini-PET, as developed by LaMilia et al.). This requires measurement of the intraperitoneal volume after drainage of the abdomen. Since valuable information of a 4-hour peritoneal equilibration test (PET) may be lost, the aim of the present study was to investigate whether temporary drainage of the peritoneal cavity after 1 hour and re-instillation thereafter would influence the results of the 4-hour PET. METHODS AND PATIENTS: Two PETs were performed in 10 stable peritoneal dialysis (PD) patients (mean age 59 +/- 13 years, mean duration on PD 33 +/- 15 months) within a mean period of 54 (range 13 - 104) days: one standardized 4-hour PET using 3.86% glucose (PET A) and one with drainage after 1 hour followed by re-instillation (PET B). RESULTS: Mean total ultrafiltration (UF) of PETs A and B was 667 +/- 210 mL and 621 +/- 206 mL (NS). Mean FWT at 60 minutes was 164 +/- 74 mL and mean UF through the small pores was 204 +/- 181 mL; FWT correlated well with total UF (r = 0.720, p = 0.019). Classification of transport categories was identical for 9 of the 10 patients. Comparison of 1-hour and 4-hour results in test B showed a good correlation between dialysate-to-plasma ratios (D/P) of creatinine and urea and D(t)/D(0) ratios of glucose. CONCLUSION: A 4-hour 3.86% glucose PET, including temporary drainage after 1 hour for assessment of free water transport, does not influence the results of D/P creatinine or D(t)/D(0) glucose and gives essential additional information on aquaporin function.

Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study.

BACKGROUND: Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited. METHODS: We examined cross-sectional Spearman's rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N∈-(carboxymethyl)lysine (CML), N∈-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-α. RESULTS: After adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI. CONCLUSIONS: In individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI.

Citric-acid dialysate improves the calcification propensity of hemodialysis patients: A multicenter prospective randomized cross-over trial.

INTRODUCTION: The concentration of dialysate calcium (dCa) has been suggested to affect vascular calcification, but evidence is scarce. Calcification propensity reflects the intrinsic capacity of serum to prevent calcium and phosphate to precipitate. The use of citric-acid dialysate may have a beneficial effect on the calcification propensity due to the chelating effect on calcium and magnesium. The aim of this study was to compare the intradialytic and short-term effects of haemodialysis with either standard acetic-acid dialysate with dCa1.50 (A1.5) or dCa1.25 (A1.25), as well as citric-acid dialysate with dCa1.50 (C1.5) in bicarbonate dialysis on the calcification propensity of serum. METHODS: Chronic stable hemodialysis patients were included. This multicenter randomized cross-over study consisted out of a baseline week (A1.5), followed by the randomized sequence of A1.25 or C1.5 for one week after which the alternate treatment was provided after a washout week with A1.5. Calcification propensity of serum was assessed by time-resolved nephelometry where the T50 reflects the transition time between formation of primary and secondary calciprotein particles. RESULTS: Eighteen patients (median age 70 years) completed the study. Intradialytic change in T50 was increased with C1.5 (121 [90-152]min) compared to A1.25 (83 [43-108]min, p<0.001) and A1.5 (66 [18-102]min, p<0.001). During the treatment week, predialysis T50 increased significantly from the first to the third session with C1.5 (271 [234-291] to 280 [262-339]min, p = 0.002) and with A1.25 (274 [213-308] to 307 [256-337]min, p<0.001), but not with A1.5 (284 [235-346] to 300 [247-335]min, p = 0.33). CONCLUSION: Calcification propensity, as measured by the change in T50, improved significantly during treatment in C1.5 compared to A1.25 and A1.5. Long-term studies are needed to investigate the effects of different dialysate compositions concentrations on vascular calcification and bone mineral disorders.

Endothelial dysfunction and low-grade inflammation in the transition to renal replacement therapy.

INTRODUCTION: End-stage renal disease (ESRD) strongly associates with cardiovascular disease (CVD) risk. This risk is not completely mitigated by renal replacement therapy. Endothelial dysfunction (ED) and low-grade inflammation (LGI) may contribute to the increased CVD risk. However, data on serum biomarkers of ED and LGI during the transition to renal replacement therapy (dialysis and kidney transplantation) are scarce. METHODS: We compared serum biomarkers of ED and LGI between 36 controls, 43 participants with chronic kidney disease (CKD) stage 5 non-dialysis (CKD5-ND), 20 participants with CKD stage 5 hemodialysis (CKD5-HD) and 14 participants with CKD stage 5 peritoneal dialysis (CKD5-PD). Further, in 34 and 15 participants repeated measurements were available during the first six months following dialysis initiation and kidney transplantation, respectively. Serum biomarkers of ED (sVCAM-1, E-selectin, P-selectin, thrombomodulin, sICAM-1, sICAM-3) and LGI (hs-CRP, SAA, IL-6, IL-8, TNF-α) were measured with a single- or multiplex array detection system based on electro-chemiluminescence technology. RESULTS: In linear regression analyses adjusted for potential confounders, participants with ESRD had higher levels of most serum biomarkers of ED and LGI than controls. In addition, in CKD5-HD levels of serum biomarkers of ED and LGI were largely similar to those in CKD5-ND. In contrast, in CKD5-PD levels of biomarkers of ED were higher than in CKD5-ND and CKD5-HD. Similarly, in linear mixed model analyses sVCAM-1, thrombomodulin, sICAM-1 and sICAM-3 increased after PD initiation. In contrast, incident HD patients showed an increase in sVCAM-1, P-selectin and TNF-α, but a decline of hs-CRP, SAA and IL-6. Further, following kidney transplantation sVCAM-1, thrombomodulin, sICAM-3 and TNF-α were lower at three months post-transplantation and remained stable in the three months thereafter. CONCLUSIONS: Levels of serum biomarkers of ED and LGI were higher in ESRD as compared with controls. In addition, PD initiation and, less convincingly, HD initiation may increase levels of selected serum biomarkers of ED and LGI on top of uremia per se. In contrast to dialysis, several serum biomarkers of ED and LGI markedly declined following kidney transplantation.

Pegylated interferon alfa-2a (40 kD) and ribavirin in haemodialysis patients with chronic hepatitis C.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with liver dysfunction and hepatocellular carcinoma. In patients with normal kidney function, treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV) frequently leads to eradication of HCV. Treatment in dialysis patients has long been controversial and until recently, the use of RBV was considered to be contra-indicated. We used plasma trough levels of RBV to promote tolerance, safety and efficacy. PEG-IFN alfa-2a (40 kD) was chosen because it is cleared predominantly via hepatic metabolism. METHODS: Seven haemodialysis patients with chronic HCV infection were eligible and started with 135 microg PEG-IFN alfa-2a (40 kD) weekly and 200 mg RBV every other day. Dose adaptations were allowed following study guidelines. Genotypes 1 and 4 (five patients) were treated for 48 weeks and genotypes 2 and 3 (two patients) for 24 weeks. HCV-RNA was determined after 12, 24 and 48 weeks (and at 72 weeks for genotypes 1 and 4). RBV trough plasma levels were monitored regularly by HPLC-technique. RESULTS: All patients completed the treatment. In two patients, the PEG-IFN dose had to be reduced to 90 microg/week because of adverse events. To achieve the target range (1.5-2.5 microg/ml) of the plasma trough level, the mean RBV dose was increased to a dose between 133 and 200 mg each day in five patients. Despite an increase of the weekly erythropoietin (Epo) dose, two to a max of four red cell transfusions were given to four patients. A sustained viral response (SVR) was reached in five patients (3/5 with genotype 1/4 and 2/2 with genotype 2/3). CONCLUSION: In our series of seven patients, we were able to use RBV monitoring drug levels in combination with PEG-IFN alfa-2a (40 kD) and achieve high sustained response rates. However, Epo and transfusion requirements may increase. In two patients adverse events were observed, but manageable with dose reduction of PEG-IFN.

Health-related quality of life in end-stage renal disease patients: the effects of starting dialysis in the first year after the transition period.

BACKGROUND/AIMS: Prevalent dialysis patients have low scores of health-related quality of life (HRQOL) which are associated with increased risk of hospitalization and mortality. Also in CKD-5 non-dialysis patients, HRQOL scores seem to be lower as compared with the general population. This study firstly aimed to compare HRQOL between CKD-5 non-dialysis and prevalent dialysis patients in a cross-sectional analysis and to assess longitudinal changes over 1 year after the dialysis initiation. Secondly, the correlation between HRQOL and physical activity (PA) was explored. METHODS: Cross-sectional 44 CKD-5 non-dialysis, 29 prevalent dialysis, and 20 healthy controls were included. HRQOL was measured by Short Form-36 questionnaires to measure physical and mental domains of health expressed by the physical component summary (PCS) and mental component summary (MCS) scores. PA was measured by a SenseWear™ pro3. Longitudinally, HRQOL was assessed in 38 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before dialysis initiation until 1 year after dialysis initiation. RESULTS: PCS scores were significantly lower both in CKD-5 non-dialysis patients and in prevalent dialysis patients as compared with healthy controls (p < 0.001). MCS scores were significantly lower in both CKD-5 non-dialysis patients (p = 0.003), and in dialysis patients (p = 0.022), as compared with healthy controls. HRQOL scores did not change significantly from the CKD-5 non-dialysis phase into the first year after dialysis initiation. PA was significantly related to PCS in both CKD-5 non-dialysis patients (r = 0.580; p < 0.001), and dialysis patients (r = 0.476; p = 0.009). CONCLUSIONS: HRQOL is already low in the CKD-5 non-dialysis phase. In the first year after dialysis initiation, HRQOL did not change significantly. Given the correlation between PCS score and PA, physical activity programs may be potential tools to improve HRQOL in both CKD-5 non-dialysis as well as in prevalent dialysis patients.

Practical Value of Anti-Xa Activity in the Evaluation of Extracorporeal Circuit Anticoagulation during Haemodialysis: Results of a Cross-Sectional Single-Centre Study.

BACKGROUND/AIMS: Anticoagulation of the extracorporeal circuit is essential for adequate haemodialysis (HD). Low molecular weight heparins (LMWHs) are safe and sufficient towards achieving this goal. In the Netherlands, dosage is based on bodyweight and adjusted based on clinical events. LMWH levels during dialysis can be quantified through measurement of the anti-Xa activity and a target range of 0.5-1.0 IU/mL has been proposed. We aimed to evaluate the practical value of the anti-Xa activity to guide LMWH dosage in HD patients. Additionally, the value of the activated partial thromboplastin time (APTT) was investigated. METHODS: All prevalent adult HD patients of our dialysis clinic were included. APTT and anti-Xa activity were measured before, during and after 2 dialysis sessions. Clinical and dialysis characteristics, including LMWH dosage, were derived from digital patient charts. RESULTS: Our final study cohort consisted of 83 patients. LMWH dosage during dialysis was appropriate for bodyweight in 61% of cases, of which 50% reached an anti-Xa activity within the putative target range of 0.5-1.0 IU/mL. Forty-six percent of patients had an anti-Xa activity >1.0 IU/mL. Anti-Xa levels during and after dialysis were significantly correlated (r = 0.803, p < 0.01). No thrombotic or haemorrhagic complications were observed in this study. Correlation of APTT with anti-Xa activity was poor. CONCLUSION: Anti-Xa activity measurements during dialysis can identify patients in whom LMWH dosage should be lowered in a subsequent dialysis session. Whether such an intervention leads to a decrease in haemorrhagic complications needs to be evaluated in prospective studies.

Physical Activity in End-Stage Renal Disease Patients: The Effects of Starting Dialysis in the First 6 Months after the Transition Period.

OBJECTIVES: Physical inactivity in end-stage renal disease (ESRD) patients is associated with increased mortality, and might be related to abnormalities in body composition (BC) and physical performance. It is uncertain to what extent starting dialysis influences the effects of ESRD on physical activity (PA). This study aimed to compare PA and physical performance between stage 5 chronic kidney disease (CKD-5) non-dialysis and dialysis patients, and healthy controls, to assess alterations in PA during the transition from CKD-5 non-dialysis to dialysis, and to relate PA to BC. METHODS: For the cross-sectional analyses 44 CKD-5 non-dialysis patients, 29 dialysis patients, and 20 healthy controls were included. PA was measured by the SenseWear™ pro3. Also, the walking speed and handgrip strength (HGS) were measured. BC was measured by the Body Composition Monitor©. Longitudinally, these parameters were assessed in 42 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before the start of dialysis and 6 months thereafter. RESULTS: PA was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. HGS was significantly lower in dialysis patients as compared to that in healthy controls. Walking speed was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. Six months after starting dialysis, activity related energy expenditure (AEE) and walking speed significantly increased. CONCLUSIONS: PA is already lower in CKD-5 non-dialysis patients as compared to that in healthy controls and does not differ from that of dialysis patients. However, the transition phase from CKD-5 non-dialysis to dialysis is associated only with a modest improvement in AEE.

Achieving high convection volumes in postdilution online hemodiafiltration: a prospective multicenter study.

Background. Available evidence suggests a reduced mortality risk for patients treated with high-volume postdilution hemodiafiltration (HDF) when compared with hemodialysis (HD) patients. As the magnitude of the convection volume depends on treatment-related factors rather than patient-related characteristics, we prospectively investigated whether a high convection volume (defined as ≥22 L/session) is feasible in the majority of patients (>75%). Methods. A multicenter study was performed in adult prevalent dialysis patients. Nonparticipating eligible patients formed the control group. Using a stepwise protocol, treatment time (up to 4 hours), blood flow rate (up to 400 mL/min) and filtration fraction (up to 33%) were optimized as much as possible. The convection volume was determined at the end of this optimization phase and at 4 and 8 weeks thereafter. Results. Baseline characteristics were comparable in participants (n = 86) and controls (n = 58). At the end of the optimization and 8 weeks thereafter, 71/86 (83%) and 66/83 (80%) of the patients achieved high-volume HDF (mean 25.5 ± 3.6 and 26.0 ± 3.4 L/session, respectively). While treatment time remained unaltered, mean blood flow rate increased by 27% and filtration fraction increased by 23%. Patients with <22 L/session had a higher percentage of central venous catheters (CVCs), a shorter treatment time and lower blood flow rate when compared with patients with ≥22 L/session. Conclusions. High-volume HDF is feasible in a clear majority of dialysis patients. Since none of the patients agreed to increase treatment time, these findings indicate that high-volume HDF is feasible just by increasing blood flow rate and filtration fraction.

Diagnosis of acute myocardial infarction in hemodialysis patients may be feasible by comparing variation of cardiac troponins during acute presentation to baseline variation.

Acute myocardial infarction (AMI) is defined as a dynamic change in cardiac troponin (cTn) with at least one cTn value exceeding the 99 th percentile of a reference population in combination with typical clinical symptoms. In hemodialysis (HD) patients, a broad range of cTn concentrations is found, partially due to patient-specific comorbidities. Therefore, the 99 th percentile cannot be used in HD patients and decision algorithms to diagnose AMI should be based on temporal variations of troponin. In this study, relative and absolute variations of cTn in a large population of asymptomatic hemodialysis patients were established during a period of 15 months. Patients were stratified according to their history of coronary artery disease (CAD). An intra-individual long term variation of 23% for cTroponin I (cTnI) and 12% for cTroponin T (cTnT) was found for patients without a history of CAD. The corresponding reference change values (RCVs) were 69% and 39% respectively. For patients with a history of CAD this variation was 29% for cTnI and 10% for cTnT, with RCVs of 86% and 35% respectively. During follow up, 27 HD patients developed an acute myocardial infarction (AMI). During these events, irrespective of CAD history, cTnI increased>172% and cTnT increased>97% above baseline cTn as measured during clinically stable periods three months separate to the event. Therefore, if a HD patient has symptoms of an acute event and a cTn increase that exceeds the RCVs described here, AMI may be suspected. If the troponin increase exceeds 172% for cTnI or 97% for cTnT, AMI is likely.

Arterial wall properties in patients with renal failure.

Hemodialysis (HD) patients commonly show abnormalities of the arterial system. Only a few studies have focused on arterial wall properties in patients with early stages of renal insufficiency and patients on peritoneal dialysis (PD) therapy. In this study, the distensibility coefficient (DC), a marker of arterial stiffening and intima media thickness (IMT) of the common carotid artery (CCA) and a surrogate marker of atherosclerosis, was assessed in four age-matched groups of patients: 18 HD patients, 36 PD patients, 30 patients with chronic renal failure (CRF) not yet on dialysis therapy with a creatinine clearance (CCl) between 10 and 70 mL/min, and 25 normotensive controls with normal renal function. Arterial wall properties were assessed by an automated vessel wall detection system. In patients with CRF and HD patients, but not PD patients, the DC of the CCA was significantly reduced (P < 0.05) compared with controls (CRF, 12.6 +/- 7.5 10(-3)/kPa; HD, 11.6 +/- 7.6 10(-3)/kPa; and PD, 14.7 +/- 6.2 10(-3)/kPa compared with controls, 16.7 +/- 4.6 10(-3)/kPa). In patients with CRF, a significant relationship was found between CCl and the DC (r = 0.41; P = 0.02). IMT was not different among patients with CRF (589 +/- 115 microm), HD (622 +/- 115 microm) and PD patients (585 +/- 121 microm), and controls (668 +/- 150 microm). In conclusion, compared with controls, the DC of the CCA was significantly reduced in HD patients and those with CRF, but not PD patients. In patients with CRF, the DC correlated significantly with CCl. IMT did not differ between groups of renal patients and controls.

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 (