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Arterial calcification is associated with cardiovascular mortality in dialysis patients. Active matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of arterial calcification. Elevated plasma concentrations of inactive MGP, i.e. dephosphorylated-uncarboxylated MGP (dp-ucMGP), are prevalent in dialysis patients. MGP inactivity might contribute to arterial calcification. We investigated whether vitamin K supplementation had an effect on arterial calcification in chronic dialysis patients.In a 2-year, double-blind, placebo-controlled intervention trial, 48 dialysis patients were randomized to vitamin K [menaquinone-7 (MK-7), 360 µg daily] or placebo. MK-7 in serum and dp-ucMGP in plasma were used to assess vitamin K status. Carotid-femoral pulse wave velocity (cfPWV) and scores of coronary arterial calcification (CAC) and abdominal aortic calcification (AAC) were used to assess arterial calcification.Thirty-seven participants completed Year 1, and 21 completed Year 2. At Year 2, serum MK-7 was 40-fold higher, and plasma dp-ucMGP 40\% lower after vitamin K supplementation compared with placebo \mean dp-ucMGP difference: −1380 pmol/L [95\CI) −2029 to −730]\. There was no significant effect of vitamin K supplementation on cfPWV [mean difference at Year 2: 1.2 m/s (95\0.1 to 2.4)]. CAC Agatston score increased significantly in vitamin K supplemented participants, but was not significantly different from placebo [mean difference at Year 2: 664 (95\554 to 1881)]. AAC scores increased in both groups, significantly so within the placebo group at Year 1, but with no significant between-group differences.Vitamin K supplementation improved vitamin K status, but did not hinder or modify the progression of arterial calcification in dialysis patients. BackgroundArterial calcification is associated with cardiovascular mortality in dialysis patients. Active matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of arterial calcification. Elevated plasma concentrations of inactive MGP, i.e. dephosphorylated-uncarboxylated MGP (dp-ucMGP), are prevalent in dialysis patients. MGP inactivity might contribute to arterial calcification. We investigated whether vitamin K supplementation had an effect on arterial calcification in chronic dialysis patients.MethodsIn a 2-year, double-blind, placebo-controlled intervention trial, 48 dialysis patients were randomized to vitamin K [menaquinone-7 (MK-7), 360 µg daily] or placebo. MK-7 in serum and dp-ucMGP in plasma were used to assess vitamin K status. Carotid-femoral pulse wave velocity (cfPWV) and scores of coronary arterial calcification (CAC) and abdominal aortic calcification (AAC) were used to assess arterial calcification.ResultsThirty-seven participants completed Year 1, and 21 completed Year 2. At Year 2, serum MK-7 was 40-fold higher, and plasma dp-ucMGP 40% lower after vitamin K supplementation compared with placebo {mean dp-ucMGP difference: −1380 pmol/L [95% confidence interval (CI) −2029 to −730]}. There was no significant effect of vitamin K supplementation on cfPWV [mean difference at Year 2: 1.2 m/s (95% CI −0.1 to 2.4)]. CAC Agatston score increased significantly in vitamin K supplemented participants, but was not significantly different from placebo [mean difference at Year 2: 664 (95% CI −554 to 1881)]. AAC scores increased in both groups, significantly so within the placebo group at Year 1, but with no significant between-group differences.ConclusionsVitamin K supplementation improved vitamin K status, but did not hinder or modify the progression of arterial calcification in dialysis patients.

To explore how patients remained involved in their treatment and care of their own health following a shared decision-making intervention for dialysis choice.A follow-up study using semi-structured interviews.Individual interviews with 13 patients were conducted immediately following their participation in a shared decision-making intervention for dialysis choice and again 3 months after initiating dialysis. This study reports findings from the follow-up interviews 3 month after dialysis initiation. Data were collected from August 2017-February 2019 and analysed using systematic text condensation.The analysis revealed five main findings, which indicated differing levels of: (a) involvement in the decision-making process; (b) involvement in treatment; (c) involvement in care of own health; (d) involvement of a relative; and (e) support from healthcare professionals.Following the shared decision-making intervention, patients who chose home-based treatment had become more involved in their treatment and care of their own health. The involvement of relatives and support from healthcare professionals contributed positively to this. In contrast, patients who had chosen hospital-based treatment were less involved in their treatment.Shared decision-making in dialysis choice has potential to improve self-management in people with kidney disease. However, support from healthcare professionals for patients and their relatives should be prioritized in an effort to increase all patients' involvement in their treatment and care of their own health.目的: 探讨在对透析选择进行共同决策干预后, 患者如何保持对自身健康的参与治疗和护理。 设计: 采用半结构式访谈进行随访研究。 方法: 在13名患者参与透析选择的共同决策干预后, 立即对他们进行了单独访谈, 并在他们开始接受透析3个月后再次对他们进行了访谈。本研究报告了透析开始3个月后的随访结果。于2017年8月至2019年2月收集数据, 并采用系统性文本压缩方式进行分析。 结果: 该分析显示了五项主要的调查结果, 这些结果表明了不同程度的参与: (a) 参与决策过程; (b) 参与治疗; (c) 参与照顾自己的健康; (d) 亲属的参与; 以及 (e) 医疗保健专业人士的支持。 结论: 在共同决策干预后, 选择在家治疗的患者在自身健康的治疗和护理工作中参与度更高。亲属的参与和医疗保健专业人士的支持对此起到了积极作用。相比之下, 选择住院治疗的患者在治疗工作方面参与度较低。 影响: 选择透析的共同决策有可能改善肾病患者的自我管理状况。不过, 应该优先考虑医疗保健专业人士对患者及其亲属的支持, 努力提高所有患者对自身健康治疗和护理工作的参与度。.

Background Patients with kidney failure experience a complex decision on dialysis modality performed either at home or in hospital. The options have different levels of impact on their physical and psychological condition and social life. The purpose of this study was to evaluate the implementation of an intervention designed to achieve shared decision-making for dialysis choice. Specific objectives were: 1) to measure decision quality as indicated by patients’ knowledge, readiness and achieved preferences; and 2) to determine if patients experienced shared decision-making. Method A mixed methods descriptive study was conducted using both questionnaires and semi-structured interviews. Eligible participants were adults with kidney failure considering dialysis modality. The intervention, based on the Three-Talk model, consisted of a patient decision aid and decision coaching meetings provided by trained dialysis coordinators. The intervention was delivered to 349 patients as part of their clinical pathway of care. After the intervention, 148 participants completed the Shared Decision-Making Questionnaire and the Decision Quality Measurement, and 29 participants were interviewed. Concordance between knowledge, decision and preference was calculated to measure decision quality. Interview transcripts were analysed qualitatively. Results The participants obtained a mean score for shared decision-making of 86 out of 100. There was no significant difference between those choosing home- or hospital-based treatment (97 versus 83; p = 0.627). The participants obtained a knowledge score of 82% and a readiness score of 86%. Those choosing home-based treatment had higher knowledge score than those choosing hospital-based treatment (84% versus 75%; p = 0.006) but no significant difference on the readiness score (87% versus 84%; p = 0.908). Considering the chosen option and the knowledge score, 83% of the participants achieved a high-quality decision. No significant difference was found for decision quality between those choosing home- or hospital-based treatment (83% versus 83%; p = 0.935). Interview data informed the interpretation of these results. Conclusions Although there was no control group, over 80% of participants exposed to the intervention and responded to the surveys experienced shared decision-making and reached a high-quality decision. Both participants who chose home- and hospital-based treatment experienced the intervention as shared decision-making and made a high-quality decision. Qualitative findings supported the quantitative results. Trial registration The full trial protocol is available at ClinicalTrials. Gov (NCT03868800). The study has been registered retrospectively.

Rationale & Objective: Arteriovenous fistulas are the preferred access type for hemodialysis. The buttonhole needling technique has become an alternative to stepladder or area puncture. However, an increased risk for infection has been described. The present study examined the risk for infectious complications with different needling techniques. Study Design: Prospective multicenter observational cohort study with 5 years of follow-up. Setting & Participants: In-center hemodialysis patients from 5 hemodialysis units in Denmark, dialyzed on a native arteriovenous fistula. 286 patients were included; 144 cannulated with the buttonhole technique. Exposure: The buttonhole cannulation technique was compared to the stepladder or area puncture technique. Outcomes: Primary end points: event rates of access-related Staphylococcus aureus bacteremia and the HR for first access-related S aureus bacteremia. Secondary end points: local infections and access-related S aureus bacteremia–related metastatic infections and mortality. Analytical Approach: Time-to-event analysis using Cox proportional hazards regression to estimate the HR of access-related S aureus bacteremia in buttonhole cannulation compared to stepladder/area puncture. Poisson regression was used for incidence rate ratio calculations. Results: S aureus caused 48 access-related bacteremias; 43 (90%) in the buttonhole group compared with 5 (10%) in the stepladder/area group. The HR for first access-related S aureus bacteremia was significantly higher for buttonhole cannulation compared to stepladder/area needling (unadjusted, 6.8 [95% CI, 2.4-19.1]; adjusted, 8.4 [95% CI, 2.9-24.2]). The incidence rate ratio for access-related S aureus bacteremia was 6.8 (95% CI, 2.9-16.1), and the incidence rate ratio of local cannulation-site infection without access-related S aureus bacteremia was 3.8 (95% CI, 1.3-15.4) for buttonhole cannulation compared to stepladder/area needling. Limitations: Nonrandomized observational design, prevalent hemodialysis patients. Conclusions: Access-related S aureus bacteremia rates were very high for buttonhole cannulation compared to stepladder/area needling, questioning the use of buttonhole cannulation in routine clinical practice. A restrictive approach to buttonhole use is recommended, with buttonhole cannulation only being used as a second alternative to area technique when stepladder cannulation is not feasible. Index Words: Dialysis, hemodialysis, end-stage renal disease, renal failure, bacteremia, Staphylococcus aureus, infection, buttonhole, cannulation, vascular access

OBJECTIVE: As blood pressure (BP) control is very important in chronic kidney disease (CKD), we investigated how office BP is influenced by the measurement circumstances and compared nonautomated self- and nurse-measured BP values.MATERIALS AND METHODS: Two hundred stage 1-5 CKD patients with scheduled visits to an outpatient clinic were randomized to either self-measured office BP (SMOBP) followed by nurse-measured office BP (NMOBP) or NMOBP followed by SMOBP. The participants had been educated to perform the self-measurement in at least one previous visit. The SMOBP and NMOBP measurement series both consisted of three recordings, and the means of the last two recordings during SMOBP and NMOBP were compared for the 174 (mean age 52.5 years) with complete BP data.RESULTS: SMOBP and NMOBP showed similar systolic (135.3 ± 16.6 vs 136.4 ± 17.4 mmHg, Δ = 1.1 mmHg, P = 0.13) and diastolic (81.5 ± 10.2 vs 82.2 ± 10.4 mmHg, Δ = 0.6 mmHg, P = 0.09) values. The change in BP from the first to the third recording was not different for SMOBP and NMOBP. In 17 patients, systolic SMOBP was ≥10 mmHg higher than NMOBP and in 28 patients systolic NMOBP exceeded SMOBP by ≥10 mmHg. The difference between systolic SMOBP and NMOBP was independent of CKD stage and the number of medications, but significantly more pronounced in patients above 60 years.CONCLUSION: In a population of CKD patients, there is no clinically relevant difference in SMOBP and NMOBP when recorded at the same visit. However, in 25% of the patients, systolic BP differs ≥10 mmHg between the two measurement modalities.

Magnetic resonance imaging (MRI) is a well-established modality for assessing renal morphology and function, as well as changes that occur during disease. However, the significant metabolic changes associated with renal disease are more challenging to assess with MRI. Hyperpolarized carbon-13 MRI is an emerging technique which provides an opportunity to probe metabolic alterations at high sensitivity by providing an increase in the signal-to-noise ratio of 20,000-fold or more. This review will highlight the current status of hyperpolarised 13C-MRI and its translation into the clinic and how it compares to metabolic measurements provided by competing technologies such as positron emission tomography (PET).

Background Troponin T (TnT) is a well-known risk factor for negative outcome in hemodialysis (HD) patients, but little is known about variation over time, and the impact of clinical and dialysis specific factors. This study investigated the effect of angiotensin II receptor blockade (ARB), short and long-term variation in TnT and associations with clinical parameters.Methods In this analysis based on the SAFIR-cohort (Clinical Trials ID: NCT00791830) 81 HD patients were randomized double-blind for placebo (n=40) or angiotensin II receptor blocker (ARB) treatment (n=41) with irbesartan (150-300 mg) and followed for 12 months with six serial measurements of TnT using a high-sensitivity assay. Results Fifty-four patients (67%) completed follow-up. Baseline TnT-medians (min-max) were (placebo/ARB): 45(14-295)/46(10-343)ng/L. ARB-treatment did not significantly affect mean TnT-levels over the 12-month study period. Median week-to-week and one-year TnT-variation (5th-95th-percentile range) using all samples regardless of intervention were: 0(-14-10)ng/L (week-to-week) and 3(-40-71)ng/L (12 months). Median TnT-amplitude, capturing the change from the lowest to the highest TnT-value observed during the one-year study period was 38% or 20.5 ng/L. Median ratios with 95% limits of agreement were: 1.00(0.73-1.37); P=0.92 (1 week/baseline; n=77) and 1.07(0.52-2.25); P=0.19 (12 months/baseline; n=54). Baseline TnT was positively correlated with diabetes, ultrafiltration volume, arterial stiffness, change in intradialytic total peripheral resistance and N-terminal pro b-type natriuretic peptide (NT-proBNP) and negatively correlated with hematocrit, residual renal function and change in intradialytic cardiac output. High baseline TnT was associated with a higher risk of admission and cardiovascular (CV) events during follow-up. Increase in TnT over time (ΔTnT=12-months-baseline) was significantly associated with increase in left ventricular (LV) mass and NT-proBNP and decrease in LV ejection fraction and late intradialytic stroke volume. ΔTnT was not significantly associated with admissions, CV or intradialytic hypotensive events during follow-up. Admissions were significantly more likely with a high (TnT-amplitude>20.5 ng/L) than a low TnT-amplitude. Peaks in TnT were less frequent in aspirin-treated patients. Conclusion ARB-treatment had no significant effect on TnT-levels. Week-to-week variation was generally low, yet over 12 months individual patients had considerable TnT fluctuations. Rise in TnT over time was significantly correlated with markers of cardiac deterioration.

Background Troponin T (TnT) is a well-known risk factor for negative outcome in hemodialysis (HD) patients, but little is known about variation over time, and the impact of clinical and dialysis specific factors. This study investigated the effect of angiotensin II receptor blockade (ARB), short and long-term variation in TnT and associations with clinical parameters. Methods In this analysis based on the SAFIR-cohort (Clinical Trials ID: NCT00791830) 81 HD patients were randomized double-blind for placebo (n = 40) or angiotensin II receptor blocker (ARB) treatment (n = 41) with irbesartan (150–300 mg) and followed for 12 months with six serial measurements of TnT using a high-sensitivity assay. Results Fifty-four patients (67%) completed follow-up. Baseline TnT-medians (min-max) were (placebo/ARB): 45(14–295)/46(10–343) ng/L. ARB-treatment did not significantly affect mean TnT-levels over the 12-month study period. Median week-to-week and one-year TnT-variation (5th–95th-percentile range) using all samples regardless of intervention were: 0(− 14–10) ng/L (week-to-week) and 3(− 40–71) ng/L (12 months). Median TnT-amplitude, capturing the change from the lowest to the highest TnT-value observed during the one-year study period was 38% or 20.5 ng/L. Median ratios with 95% limits of agreement were: 1.00(0.73–1.37); P = 0.92 (1 week/baseline; n = 77) and 1.07(0.52–2.25); P = 0.19 (12 months/baseline; n = 54). Baseline TnT was positively correlated with diabetes, ultrafiltration volume, arterial stiffness, change in intradialytic total peripheral resistance and N-terminal pro b-type natriuretic peptide (NT-proBNP) and negatively correlated with hematocrit, residual renal function and change in intradialytic cardiac output. High baseline TnT was associated with a higher risk of admission and cardiovascular (CV) events during follow-up. Increase in TnT over time (ΔTnT = 12-months-baseline) was significantly associated with increase in left ventricular (LV) mass and NT-proBNP and decrease in LV ejection fraction and late intradialytic stroke volume. ΔTnT was not significantly associated with admissions, CV or intradialytic hypotensive events during follow-up. Admissions were significantly more likely with a high (TnT-amplitude> 20.5 ng/L) than a low TnT-amplitude. Peaks in TnT were less frequent in aspirin-treated patients. Conclusion ARB-treatment had no significant effect on TnT-levels. Week-to-week variation was generally low, yet over 12 months individual patients had considerable TnT fluctuations. Rise in TnT over time was significantly correlated with markers of cardiac deterioration. Trial registration ClinicalTrials.gov Identifier: NCT00791830. Date of registration: November 17, 2008. EudraCT no: 2008–001267-11.

Background Evidence is inconclusive on how best to guide the patient in decision-making around haemodialysis and peritoneal dialysis choice. International guidelines recommend involvement of the patient in the decision to choose the dialysis modality most suitable for the individual patient. Nevertheless, studies have shown lack of involvement of the patient in decision-making. Objectives To develop and pilot test an intervention for shared decision-making targeting the choice of dialysis modality. Methods This study reflects the first two phases of a complex intervention design: phase 1, the development process and phase 2, feasibility and piloting. Because decision aids were a part of the intervention, the International Patient Decision Aid Standards were considered. The pilot test included both the intervention and the feasibility of the validated shared decision-making questionnaire (SDM Q9) and the Decision Quality Measure (DQM) applied to evaluate the intervention. Results A total of 137 patients tested the intervention. After the intervention, 80% of the patients chose dialysis at home reflecting an increase of 23% in starting dialysis at home prior to the study. The SDM Q9 showed the majority of the patients experienced this intervention as shared decision-making. Conclusion An intervention based on shared decision-making supported by decision aids seemed to increase the number of patients choosing home dialysis. The SDM Q9 and DQM were feasible evaluation tools. Further research is needed to gain insight into the patients' experiences of involvement and the implications for their choice of dialysis modality.

ObjectiveTo evaluate the ‘Shared Decision-making and Dialysis Choice’ (SDM-DC) intervention with regard to patients’ experience and involvement.DesignSemistructured individual interviews and systematic text condensation for data analysis.SettingThe SDM-DC intervention was implemented and evaluated at four different hospitals in Denmark.ParticipantsA total of 348 patients had received the SDM-DC intervention, and of these 29 patients were interviewed.InterventionsSDM-DC was designed for patients facing a choice of dialysis modality. The available modalities were haemodialysis and peritoneal dialysis, either performed by patients on their own or with help from a healthcare professional. The intervention was tailored to individual patients and consisted of three meetings with a dialysis coordinator who introduced a patient decision aid named ‘Dialysis Choice’ to the patient.FindingsThe following were the four main findings: the decision was experienced as being the patient’s own; the meetings contributed to the decision process; ‘Dialysis Choice’ contributed to the decision process; and the decision process was experienced as being iterative.ConclusionsThe patients experienced SDM-DC as involving them in their choice of dialysis modality. Due to the iterative properties of the decision-making process, a shared decision-making intervention for dialysis choice has to be adapted to the needs of individual patients. The active mechanisms of the meetings with the dialysis coordinator were (1) questions to and from the patient, and (2) the dialysis coordinator providing accurate information about the options. The overview of options and the value clarification tool in the decision aid were particularly helpful in establishing a decision-making process based on informed preferences.

Magnetic resonance imaging (MRI) is a well-established modality for assessing renal morphology and function, as well as changes that occur during disease. However, the significant metabolic changes associated with renal disease are more challenging to assess with MRI. Hyperpolarized carbon-13 MRI is an emerging technique which provides an opportunity to probe metabolic alterations at high sensitivity by providing an increase in the signal-to-noise ratio of 20,000-fold or more. This review will highlight the current status of hyperpolarised

Background: Troponin T (TnT) is a highly specific biomarker for myocardial infarction (MI). Haemodialysis (HD) patients often have increased arterial stiffness and elevated TnT. Previous studies have linked elevated TnT with worse outcome, even in the absence of MI. The aim of this study was to evaluate whether arterial stiffness affects TnT-levels in stable HD-patients. Methods: Eighty-one HD-patients recruited as part of the SAFIR-study with urine output >300 mL/day, HD-vintage 30% were followed for 12 months with serial measurements of TnT using a high-sensitivity assay and carotid-femoral pulse wave velocity (cfPWV). Results: At baseline, cfPWV was positively correlated with natural log-transformed TnT (logTnT) and by splitting cfPWV into tertiles (see Figure) the geometric baseline TnT-means with 95% confidence intervals (95%-CI) were: cfPWV12.5 m/s (n = 26): 59(44–78) ng/L (P = 0.03 in ANOVA-test for difference between groups). Baseline cfPWV-tertiles remained significantly correlated with logTnT in multivariate analysis (adjusted for haematocrit, EF, NT-proBNP, ultrafiltration volume and Charlson comorbidity index). Higher TnT-levels at baseline were associated with a higher risk of admission and cardiovascular events during follow-up with logTnT odds-ratios (95%-CI): 2.62(1.22–5.64) and 2.25(1.04–4.86). Increase in TnT over time was significantly correlated with increase in LV-mass and NT-proBNP and decrease in LVEF and late intradialytic stroke volume, but it was not significantly associated with increase in cfPWV. Conclusions: Increased arterial stiffness was associated with higher TnT-levels. Rise in TnT over time was significantly correlated with deterioration of cardiac status.

Introduction Health related quality of life (HRQOL) is markedly reduced in hemodialysis patients compared to the general population. We investigated the course of self-reported HRQOL over time and the association with selected factors, focusing on changes in glomerular filtration rate (GFR). Methods Eighty-two newly started hemodialysis patients from the SAFIR cohort filled out the Kidney Disease Quality of Life Short Form Version 1.3 (KDQOL-SFTM) questionnaire at baseline, 6 and 12 months. The SAFIR study was a randomized, placebo-controlled, double-blind intervention study, examining the effects of the angiotensin II receptor blocker irbesartan. HRQOL was a secondary outcome measure. Main inclusion criteria: Dialysis vintage 30% and urinary output >300 mL/day. GFR was measured with mean creatinine and urea clearance from 24-hour urine collections at baseline, 6 and 12 months. Findings Irbesartan treatment did not affect HRQOL. Patients were pooled into one group for further analyses. Decline in GFR correlated significantly with decreasing HRQOL over time. HRQOL was stable over time, with a slight nonsignificant tendency toward improved HRQOL. The largest HRQOL-differences (positive values equal improved HRQOL) observed during the 12 month study period were (mean[95% confidence interval]): Burden of kidney disease:6.4[−2.2;15.0], Role limitations-physical:12.7[−2.1;27.5], and Role limitations-emotional:9.7[−5.2;24.6]. Comorbidity, especially diabetes, hospital admissions, female gender, and age were strongly associated with lower HRQOL in cross sectional analysis. Discussion Preservation of residual renal function seems to be important for HRQOL. In newly started HD patients, HRQOL showed little change after 12 months. HRQOL was negatively affected by comorbidity, especially diabetes, hospital admissions, female gender, and age.

Introduction: Low-grade chronic inflammation is common in hemodialysis (HD) patients. Previous studies suggest an anti-inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB vs. placebo on plasma concentrations of inflammatory markers in HD patients. Methods: Adult HD patients were randomized for double-blind treatment with the ARB irbesartan 150–300 mg/day or placebo. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C-reactive protein (hsCRP), interleukin (IL)−1β, IL-6, IL-8, IL-18, and transforming growth factor-β (TGF-β) were measured using Luminex and enzyme-linked immunosorbent assay (ELISA) technology. Findings: Eighty-two patients were randomized (placebo/ARB: 41/41). The groups did not differ in initial levels of any of the inflammatory markers (placebo/ARB median(range)): hsCRP 3.3(0.2–23.4)/2.7(0.2–29.6) μg/mL; IL-1β 1.1(0.0–45.9)/1.1(0.0-7.2) pg/mL; IL-6 10(1–90)/12(1–84) pg/mL; IL-8 31(9–134)/34(5–192) pg/mL; IL-18 364(188–1343)/377(213–832) pg/mL; TGF-β 3.2(0.8–13.9)/3.6(1.3–3.8) ng/mL. Overall, there was no significant difference in hsCRP, IL-6, IL-8, and TGF-β between placebo and ARB-treated patients during the study period, and hsCRP, IL-6, IL-8, and TGF-β were relatively stable during the study period (P ≥ 0.18 in all tests for parallel curves, equal levels, and constant levels). The IL-1β level was slightly different in the two groups over time, but not significantly (P = 0.09 in test for parallel curves) and it was also relatively stable during the study period (P ≥ 0.49 in tests for equal levels and constant level). IL-18 was the only inflammatory marker which was not constant during the study period (P = 0.001 in test for constant level), but there was no significant difference between placebo and ARB-treated (P ≥ 0.51 in tests for parallel curves and equal levels). Discussion: Inflammatory biomarkers were neither acutely, nor in the long-term significantly affected by the ARB irbesartan. Our findings suggest that ARB treatment in HD patients does not offer protective anti-inflammatory effects.

BACKGROUND: Glomerular filtration rate (GFR) declines during long-term dialysis treatment. In peritoneal dialysis, blockade of the renin-angiotensin-aldosterone system reduces GFR decline. Observational studies suggest that similar treatment may preserve kidney function in hemodialysis (HD).STUDY DESIGN: A multicenter, randomized, placebo-controlled, double-blinded trial, with 1-year follow-up.SETTING & PARTICIPANTS: Adult HD patients with urine output >300mL/24h, HD vintage less than 1 year, and cardiac ejection fraction >30%. Patients were included from 6 HD centers.INTERVENTION: Patients were randomly assigned to placebo or the angiotensin II receptor blocker irbesartan, 300mg daily. Target systolic blood pressure (BP) was 140mm Hg.OUTCOMES MEASUREMENTS: Primary outcomes were change in GFR measured as the mean of creatinine and urea renal clearance together with urine volume. Secondary outcomes were change in albuminuria, renin-angiotensin II-aldosterone hormone plasma levels, and time to anuria.RESULTS: Of 82 patients randomly assigned (41 patients in each group), 56 completed 1 year of treatment. The placebo and irbesartan groups were comparable at baseline in terms of sex balance (26 vs 30 men), mean age (62 vs 61 years), median HD vintage (137 vs 148 days), mean HD time (10 vs 11h/wk), median urine volume (1.19 vs 1.26L/d), and mean GFR (4.8 vs 5.7mL/min/1.73m(2)). The target BP level was reached in both groups and BP did not differ significantly between groups over time. Adverse-event rates were similar. GFR declined by a mean of 1.7 (95% CI, 1.2-2.3) and 1.8 (95% CI, 1.1-2.4) mL/min/1.73m(2) per year in the placebo and irbesartan groups, respectively. Mean difference (baseline values minus value at 12 months) between groups was -0.0 (95% CI, -0.8 to 0.8). In each group, 4 patients became anuric.LIMITATIONS: GFR decline rates were lower than expected, reducing the power.CONCLUSIONS: At equal BP levels, we found that irbesartan treatment did not affect the decline in GFR or urine volume significantly during 1 year of treatment in HD patients. Irbesartan treatment was used safely in the studied population.

Osmotic changes in plasma are assumed to cause cerebral swelling in hemodialysis patients. We investigated the acute effect of low-flux hemodialysis (HD) (removal of small molecules) and pre-dilution hemodiafiltration (pre-HDF) (additional removal of larger molecules) on cerebral compartment volumes using quantitative magnetic resonance imaging (MRI) in chronic uremic patients. Twelve patients underwent a session of HD and pre-HDF in a randomized crossover study with equal ultrafiltration. MRI was performed immediately before and after dialysis. A linear correlation was found between changes in gray matter and plasma osmolarity (HD: rsup2/sup= 0.83; HDF: rsup2/sup = 0.73) but not between changes in white matter volume and plasma osmolarity (HD: rsup2/sup = 0.02; HDF: rsup2/sup = 0.004). Total brain volume increased by 1.8 ± 1.7% (18.7 ± 17.4 mL) (mean ± SD) during HD and 2.0 ± 0.9% (22.3 ± 10.7 mL) during pre-HDF. Gray matter volume increased: HD 3.8% (from -3.6 to 9.7) and pre-HDF 4.2% (from -2.8 to 14.3). White matter volume did not change significantly. Reduction ratio of urea (molecular weight (MW) 0.06 kDa) (HD: 68%; pre-HDF: 69.7%) and β2-microglobulin (MW 11.7 kDa) (HD: -13.7%; pre-HDF: 67.2%) separated the treatments. This study showed that HD and pre-HDF caused equal acute cerebral swelling of the grey matter. This appeared to be driven by small solute change in plasma interacting linearly with gray matter volume regardless of additional removal of larger molecules or ultrafiltration. .

Objective This method comparison study, conducted at the peritoneal dialysis (PD) outpatient clinic of the Department of Renal Medicine, Aarhus University Hospital, Denmark, set out to evaluate the accuracy and reproducibility of methods for estimating glomerular filtration rate (GFR) based on endogenous markers in PD patients. Patients The 12 consecutive patients included in the study were examined twice while in a stable condition. All patients finished the study. Inclusion criteria were age 18 years or older, ability to collect 24-hour urine, and urine production greater than 300 mL in 24 hours. Main Outcome Measures The methods for estimating GFR using endogenous markers included the average of urinary clearances of creatinine and urea [U-Cl(crea–urea)] and two equations using the serum concentration of cystatin C [eGFR(CysC)]. The resulting GFR estimates were compared with those obtained using urinary and corrected plasma clearances of 51Cr-EDTA [U-Cl(EDTA) and cP-Cl(EDTA)], the corrected plasma clearance being plasma clearance minus dialysate clearance. Results Compared with the U-Cl(EDTA), the U-Cl(crea–urea) GFR estimate was 12% higher [95% confidence limits (CL): 3%, 21%]. Although significantly different ( p = 0.01), the latter two methods showed the best agreement. The estimates obtained using the eGFR(CysC) methods were skewed from y = x compared with the estimates obtained using other methods, indicating strong bias, probably because of extrarenal elimination. The cP-Cl(EDTA) estimate was 34% (95% CL: 26%, 42%), higher than the U-Cl(EDTA) estimate ( p < 0.001). The reproducibility (coefficients of variation) differed significantly between methods: cP-Cl(EDTA), 7%; U-Cl(EDTA), 14%; U-Cl(crea–urea), 18%; and both eGFR(CysC) methods, 3%. Conclusions In PD patients, GFR may be estimated as U-Cl(crea–urea) when complete urine collection is performed, taking into account an overestimation of approximately 12%. The available equations for eGFR(CysC) seem to be inaccurate; further development and validation is desirable. Omitting the eGFR(CysC) methods, cP-Cl(EDTA) was the most reproducible method and might be useful in certain situations.

The purpose of the investigation was to study the metabolism of erythropoietin (EPO) in patients with liver disease. Twelve patients with liver cirrhosis and 10 healthy volunteers were studied. The patients were moderately anemic with a hematocrit of 33 vs 42% (medians) in the volunteers. The pharmacokinetic parameters were calculated after an intravenous (i.v.) injection of 100 U/kg of recombinant human EPO. The serum EPO was measured by radioimmunoassay at regular intervals until 48 h. The median terminal elimination half life in the cirrhosis patients was 5.15 h vs 5.37 h in the control subjects. The clearance was 7.78 vs 7.52 ml/min/1.73 m2 (ns). The steady-state volume of distribution was 3.69 vs 3.09 1/1.73 m2 (ns). The estimated endogenous EPO production was significantly higher in liver cirrhosis (486 vs 290 U/d/1.73m2, p < 0.01). The basal serum EPO was significantly higher in the cirrhosis patients (43.5 vs 26.3 U/l, p < 0.01). The hematocrit correlated inversely with the basal serum EPO level in the cirrhosis patients (r = -0.63, p < 0.04). The EPO-clearance was not related to the presence of ascites, esophageal varices, or to abnormal blood chemistry. It was concluded that normal metabolism of EPO was maintained in liver cirrhosis and that the cirrhotic patients had a moderate compensatory increase of EPO production in response to anemia.

Background: It is the prevailing view that convective dialysis techniques stabilize blood pressure. The aim of this study was to compare the hemodynamics of high-dose predilution hemodiafiltration (HDF) and low-flux hemodialysis (HD), under matched conditions and using high calcium-ion concentration in the replacement/dialysis fluid. Methods: 13 stable hemodialysis patients were investigated in a randomized crossover, blinded controlled trial. The patients were allocated to one session of predilution HDF (substitution fluid 1.20 1/kg BW) and one session of HD at 4.5 hours. At the start of the dialysis the patient's core temperature was "locked" by an automatic feedback system regulating the dialysate temperature, thereby patient's temperature was kept stable throughout the whole treatment. The Ca ion concentration in the substitution/dialysis fluid was 1.75 mM. Cardiac output was measured hourly by the ultrasound velocity dilution method. Results: Within treatments comparisons revealed that both treatments displayed stable mean blood pressure and equally reduced cardiac output. HDF showed decreased stroke volume and increased total peripheral resistance. The pulse rate decreased significantly only during HD. Arterial temperature was kept constant during both treatments. Ultrafiltration volume, cardiopulmonary recirculation, relative blood volume, Kt/V and total energy transfer were matched for HD and HDF. The overall between treatments comparisons revealed no significant differences. Conclusions: We have shown that during matched conditions and high calcium concentrations, the hemodynamic profiles of high dose predilution HDF and lowflux HD were similar. Both modalities showed stable mean blood pressure profiles. An acute circulatory benefit of convective solute removal over diffusive, could not be demonstrated.

Background/Aim: Hemodialysis using high cutoff (HCO) filters possibly improves renal function in diseases with light chain (LC) overproduction and acute kidney injury. We established the effect of HCO dialysis on renal outcome in consecutive patients with malignant monoclonal gammopathies and LC cast nephropathy. Methods: LC concentration was measured before and after each dialysis session in 10 patients receiving HCO dialysis and bortezomib-based chemotherapy, and their renal function was monitored by plasma creatinine. Results: The number of HCO sessions ranged from 4 to 34 (mean 13). Six patients recovered kidney function, 3 regained partial function while 1 patient continued chronic dialysis. Patients with the largest reductions in LC during HCO treatments had the lowest creatinine at 6 and 9 months of follow-up. For comparison, only 2 out of 10 patients in a historic control group recovered kidney function. Conclusion: HCO dialysis combined with bortezomib results in good renal recovery with kidney function being dependent on the degree of LC lowering.

IntroductionHaemodialysis (HD) patients are exposed to various endogenous and exogenous factors, which in their sum contribute to a chronic inflammatory state evidenced by increased levels of pro-inflammatory cytokines. The renin-angiotensin-aldosterone system (RAAS) has important modulating activities in inflammation, and previous studies suggest an anti-inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB versus placebo on plasma concentrations of inflammatory markers in HD patients. MethodsAdult HD patients were randomised for double-blind treatment with the ARB irbesartan 150 mg or placebo. After two weeks, daily dose was increased to 300 mg/day. Patients receiving RAAS-blocking agents at inclusion stopped this treatment one week before baseline. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C-reactive protein (hsCRP), interleukin (IL) 1β, IL-6, IL-8, IL-18, and transforming growth factor β (TGF-β) were measured using Luminex immunoassay technology. Data were analysed based on a multivariate repeated measurements model (xtmixed) with time and drug (placebo or irbesartan) and the interaction between them as factors using Stata/IC 12.1. ResultsEighty-two patients were randomised (placebo/irbesartan: 41/41) and 56 completed one year of treatment. The groups (placebo/irbesartan) were comparable at baseline (mean±SD): Males 26(63%)/30(73%); age 62±14/61±16 years; systolic blood pressure (BP) 145±19/148±21 mmHg; HD vintage 168±95/171±93 days; HD time 10±2/11±3 hr/week; urine output 1.3±0.7/1.5±0.8 L/24 h; glomerular filtration rate 4.8/5.7 mL/min/1.73m2. Predialysis systolic BP decreased to the same extent in the irbesartan (–10 mm Hg) and in the placebo arm (–8 mm Hg). Use of additional antihypertensive drugs, ultrafiltration volume and HD dosage were similar during follow-up. Baseline levels of inflammatory markers (median with range) were similar hsCRP 3.3(0.2-23.4)/2.7(0.2-29.6) μg/mL; IL-1β 1.1(0.0-45.9)/1.1(0.0-7.2) pg/mL; IL-6 10(1-90)/12(1-84) pg/mL; IL-8 31(9-134)/34(5-192) pg/mL; IL-18 364(188-1343)/377(213-832) pg/mL; TGF-β 3.2(0.8-13.9)/3.6(1.3-13.8) ng/mL. Overall, there was no significant difference in hsCRP, IL-6, IL-8, and TGF-β between patients receiving placebo, and irbesartan treated patients during the study period, and hsCRP, IL-6, IL-8, and TGF-β were relatively stable during the study period (P≥0.18 in all tests for parallel curves, equal levels, and constant levels). The IL-1β level was slightly different in the two groups over time, but not significantly (P=0.09 in test for parallel curves) and it was also relatively stable during the study period (P=0.71 in test for equal levels and P=0.49 in test for constant level). The IL-18 level, however, was not constant during the study period (P=0.001 in test for constant level), but there was no significant difference between placebo and irbesartan treated (P=0.58 in tests for parallel curves and P=0.51 in test for equal levels). ConclusionsNo significant short-term or long-term anti-inflammatory effect of irbesartan treatment was observed. Our findings suggest that in HD patients antihypertensive treatment with irbesartan (and most likely ARBs in general) does not have clinically relevant BP-independent effects that favourably impact on inflammation.

Predilution hemodiafiltration displays no hemodynamic advantage over low-flux hemodialysis under matched conditions. Background It is the prevailing view that convective dialysis techniques stabilize blood pressure. The aim of this study was to compare the intrasession hemodynamics during high-dose predilution hemodiafiltration (HDF) and low-flux hemodialsis, under strict controlled conditions. Methods Twelve stable hemodialysis patients were investigated in a randomized crossover blinded controlled trial. The patients were allocated to one session of predilution HDF (substitution fluid 1.20 ± 0.10 L/kg body weight) and one session of hemodialysis at 4½ hours. To eliminate confounding factors, dialysis dose, ultrafiltration volume and arterial temperature were matched. At the start of the dialysis the patients' core temperature was "locked" by an automatic feedback system regulating the dialysate temperature; thereby, patients' temperature was kept stable throughout the whole treatment. The calcium-ion concentration in the substitution/dialysis fluid was 1.25mmol/L. Cardiac output was measured hourly by the ultrasound velocity dilution method. Results Mean blood pressure, cardiac output, stroke volume, cardiac work, and relative blood volume was significantly reduced in both treatments. Total peripheral resistance increased significantly in both groups. Ultrafiltration volume, cardiopulmonary recirculation, Kt/V, and total energy transfer were similar for hemodialysis and HDF. The pulse rate showed no significant change throughout both sessions. No significant differences were revealed between hemodialysis and HDF. Conclusion The hemodynamics of predilution HDF and low-flux hemodialysis displayed a similar profile during matched conditions. An acute circulatory benefit of convective solute removal over diffusive could not be demonstrated.

Background: Glomerular filtration rate (GFR) declines during chronic dialysis treatment. In peritoneal dialysis, blockade of the renin-angiotensin-aldosterone system reduces GFR decline. Observational studies suggest that similar treatment may preserve renal function in hemodialysis (HD).Methods: The SAFIR study is a multicenter randomized placebo-controlled double-blinded trial initiated by the investigators with one-year follow-up. Inclusion criteria were adult HD patient with urine output > 300 mL/24h, HD vintage < 1 year, and cardiac ejection fraction > 30%. Patients were included from six HD centers and randomized to placebo or the angiotensin II receptor blocker irbesartan 300 mg daily. Target systolic blood pressure (BP) was 140 mmHg. Outcomes were GFR measured as the mean of creatinine and urea renal clearance, urine volume and time to anuria.Results: Of the 82 patients randomized (placebo n=41/irbesartan n=41), 56 completed one year of treatment. The groups were comparable at baseline (means): males 26/30, age 62/61 years, HD vintage 137/148 days (medians), HD time 10/11 hours/week, urine volume 1.19/1.26 L/24h (medians), GFR 4.8/5.7 mL/min/1.73m2. The target BP level was reached in both groups and BP did not differ significantly between groups over time. Adverse event rates were similar. GFR declined by 1.7 (1.2 to 2.3) (mean (95% CI)) mL/min/1.73m2/year in the placebo group and by 1.8 (1.1 to 2.4) mL/min/1.73m2/year in the irbesartan-treated group. Mean difference (baseline-12 months) between groups was -0.0 (-0.8 to 0.8). In each group, four patients became anuric.Conclusions: At equal BP levels, we found that irbesartan treatment did not affect the decline in GFR or urine volume significantly during one-year treatment in HD patients. Irbesartan treatment was safely used in the studied population.

Summary Background Residual renal function in haemodialysis patients is of increasing interest. However, reproducibility and agreement between methods to measure and estimate glomerular filtration rate (GFR) require further elucidation. The aim of this study was to evaluate the accuracy and reproducibility of GFR estimates based on endogenous markers in haemodialysis patients. Methods Twelve patients were examined twice. GFR was estimated by (i) urine clearances of creatinine, urea and the average of creatinine and urea clearance [U-Cl(crea-urea)]; (ii) an equation based on serum concentration of cystatin C [eGFR(CysC)]. These were compared to 51Cr-EDTA clearance in plasma [P-Cl(EDTA)] and urine [U-Cl(EDTA)]. Results U-Cl(crea-urea) produced results similar to U-Cl(EDTA). eGFR(CysC) had a low week-to-week variability. Visually, eGFR(CysC) differed from y = x when compared to the other methods indicating bias, probably due to extrarenal elimination of cystatin C. Coefficients of variation were significantly different, P

Purpose Tunneled catheters used for hemodialysis treatment often become dysfunctional due to deposition of clotting material within the catheter lumen. In a retrospective study design we investigated the effect of mechanical brushing of dysfunctional tunneled catheters using a metal guide wire with simultaneous installation of urokinase. Materials and Methods During a period of 26 months all together 24 different catheters in 21 chronic hemodialysis patients were brushed due to insufficient blood flow or increased arterial or venous line pressures resulting in repeated alarms during dialysis treatments. Results Median functional survival after brushing was 45 days with 8 catheters being exchanged (n=5) or rebrushed (n=3) within 10 dialysis sessions (4 weeks). After 2 months all together 13 (54%) catheters were exchanged due to repeated dysfunction and by 3 months functional survival was only about 35%. The catheters needing exchange were characterized by low flow and high arterial line resistance already in the dialysis sessions immediately following the brushing procedure. Median survival of the exchanged catheters was considerably longer (>400 days) as compared to the brushed catheters. Conclusions In conclusion mechanical brushing of dysfunctional tunneled hemodialysis catheters can prolong short term function but only affects long term catheter survival in a minority of the patients.

Summary The purpose of this study was to investigate the influence of prolonged treat­ ment with recombinant human erythropoietin (epoetin) on the pharmacokinetics of epoetin in dialysis patients. 12 patients (male/female: 6/6, median age 44 years) with end-stage renal failure were investigated. Five were treated with continuous ambulatory peritoneal dialysis and 7 with haemodialysis. The pharmacokinetics were studied in each patient after an intravenous and a subcutaneous dose of epoetin 100 U/kg before regular treatment with epoetin was instituted. The in­ vestigation was repeated in the same patients after a median of 8 months of regular epoetin treatment. The haematocrit count increased from 25 to 33% (medians). The intravenous elimination half-life (8.23 vs 7.96 hours), intravenous mean residence time (ll.S vs 11.2 hours), clearance (0.31 vs 0.32 Llhf1.73 m2), sub­ cutaneous maximal concentration (108 vs 123 U/L) at 19 vs 12 hours, and bio­ availability (20.8 vs 21.6%) did not change significantly after prolonged epoetin treatment. The volume of distribution was slightly reduced from 3.76 to 3.46 LlI.73m2. The estimated absorption half-life (25.1 vs 16.7 hours), the mean input time (29.0 vs 29.9 hours), and the mean residence time (42.5 vs 40.1 hours) after subcutaneous application did not change significantly. The estimated endogenous epoetin production was unchanged at 144 vs ISS U/day/1.73m2. The loss of epoetin in the peritoneal dialysis bags was below 2.3% of the dose. In conclusion, except for a small reduction in the volume of distribution, long term treatment with epoetin had no influence on the intravenous or subcutaneous pharmacokinetics of epoetin in dialysis patients. No compensatory adjustment of the native epoetin production was detected.

The purpose of this study was to investigate the metabolism of erythropoietin (EPO) in uremia compared with healthy subjects. Twenty-one patients (nine men and 12 women) with end-stage renal failure and anemia and 12 healthy volunteers (3 women and nine men) were studied. The pharmacokinetic parameters were calculated after an i.v. and a femoral sc injection of 100 U/kg of recombinant human EPO. The serum EPO (s-EPO) was measured by radio-immunoassay at regular intervals until 48 h (i.v.) and 120 h (sc). In uremia, the median terminal elimination half-life was significantly longer (8.31 versus 4.92 h; P0.001) and the clearance was reduced (5.00 versus 7.88 mL/min per 1.73 m2; P0.01). The volume of distribution was (3.70 versus 3.31 L/1.73 m2) not significant. The estimated endogenous EPO production was significantly lower in uremia (146 versus 290 U/day per 1.73 m2; P0.001). After sc administration, the bioavailability was significantly lower in the patients (23.7 versus 38.5%; P0.01), and the maximal s-EPO was lower (113 versus 153 U/L; P0.05) and delayed (15.4 versus 11.0 h; P0.02), but the mean input time (sc) was not significantly different (23.3 versus 27.8 h). The basal s-EPO was lower in the uremic patients (20.0 versus 26.3 U/L; P0.05). There was no difference between patients treated with hemodialysis and peritoneal dialysis or between uremic men and women. There was no correlation between the pharmacokinetic parameters and age.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose. In dialysis patients, longer survival is associated with a higher residual renal function. Randomized controlled trials are conducted to clarify how residual renal function can be preserved. However, existing methods for measuring residual renal function are uncertain and there is a need for establishing a standard for measurements of glomerular filtration rate (GFR) in dialysis patients. Methods. (51)Cr-EDTA clearances in plasma, urine, and dialysate were evaluated in a sample of 12 hemodialysis and 12 peritoneal dialysis patients. The patients' condition was generally stable, and all patients were investigated twice within 4-10 days. Results. Plasma clearances of (51)Cr-EDTA for all patients ranged between 2.1 and 30.8 mL/min/1.73m(2), whereas urinary (51)Cr-EDTA clearances ranged from 0.7-20.0 mL/min/1.73m(2). This difference was statistically significant (p

In order to evaluate the hormonal regulation of blood pressure (BP) in uraemia 12 patients on chronic maintenance dialysis and 14 healthy controls were studied. BP and plasma concentrations of atrial natriuretic peptide (ANP), cyclic 3',5'-guanosine monophosphate (cGMP), and intact parathyroid hormone (PTH(1-84)) were determined before, during, and after a 60 min noradrenaline infusion 0.1 micrograms kg-1 body wt. min-1. Mean BP increased to the same extent in the uraemic patients (median 15 mmHg, range 6-25 mmHg) as in the controls (12 mmHg, 5-25 mmHg). ANP increased during noradrenaline infusion both in patients (7.2 to 8.3 pmol/l, medians, p0.01) and in controls (4.4 to 6.0 pmol/l, p0.01), and so did cGMP (patients: 31.6 to 35.9 nmol/l, p0.05; controls: 6.6 to 8.7 nmol/l, p0.01). PTH(1-84) was higher in the uraemic patients than in the controls, but was unchanged during noradrenaline infusion in both groups. Correlation analyses gave no evidence of a direct relation between BP and ANP, but basal PTH(1-84) was negatively correlated to basal mean BP in the patients (rho = -0.615, p0.05), but not in the controls. In conclusion, noradrenaline induced similar elevations of BP in dialysis patients as in healthy controls despite elevated ANP and PTH(1-84) in the patients, and ANP release was stimulated in both groups. PTH(1-84) may participate in blood pressure regulation in uraemic patients.

BACKGROUND: It is generally accepted that peritoneal dialysis (PD) affects systemic haemodynamics less than haemodialysis, but little is known about changes in haemodynamics during PD. It is unknown if increasing PD volume causes changes in cardiovascular haemodynamics possibly increasing the demand on the heart even during normal daily activities. METHODS: Fifteen stable PD patients were included in this randomized, controlled, open-label crossover study. After drainage, we measured blood pressure, pulse rate and cardiac output (CO) after 30 min in the supine position. The measurements were repeated 5 min later in an upright position. Subsequently, following fill, the measurements were repeated after 30 min in the supine and 5 min later in the upright position. The two procedures were repeated twice. The fill was either 2 l or 3 l of dialysate. CO was measured with a non-invasive device based on foreign gas rebreathing. Stroke volume (SV) and total peripheral systemic resistance were calculated. RESULTS: In the supine position, no difference was found between drained and 2 l fill. With 3 l fill both SV and CO decreased and total peripheral systemic resistance increased, while pulse rate and mean arterial blood pressure remained unchanged. In the upright position, SV and CO decreased and total peripheral systemic resistance increased. Pulse rate and mean arterial blood pressure were unchanged independent of fill volume when compared with the drained situation. During postural change, no significant differences were found between drained and 2 l and 3 l fill. CONCLUSION: The present study showed that cardiac performance decreased when increasing fill volume from 2 to 3 l in the supine position. The decreased cardiac performance was already present after 2 l fill in the upright position and did not change negatively by increasing fill. It was also shown that cardiovascular response from the supine to upright position was preserved. Udgivelsesdato: 2007-Oct

BACKGROUND AND AIM: Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan.DESIGN: Randomized, double-blind, placebo-controlled, one-year intervention trial.SETTING AND PARTICIPANTS: Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage INTERVENTION: Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients.OUTCOMES AND MEASUREMENTS: Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension.RESULTS: At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters.CONCLUSION: Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen.TRIAL REGISTRATION: Clinicaltrials.gov NCT00791830.

BACKGROUND: It is the prevailing view that convective dialysis techniques stabilize blood pressure. Calcium concentration in the substitution fluid may be important in this respect. The aim of this study is to investigate the influence of calcium ion concentration in the substitution fluid on hemodynamic stability during predilution hemofiltration (HF). METHODS: We conducted a randomized, crossover, blinded, controlled trial with 12 stable long-term hemodialysis patients without diabetes. Each patient was randomly assigned to substitution fluid with a calcium ion (iCa) concentration of 2.5 mEq/L (1.25 mmol/L; low-calcium session [L-HF]) or 3.5 mEq/L (1.75 mmol/L; high-calcium session [H-HF]) during 4.5 hours of predilution HF with a volume of 1.24 +/- 0.09 L/kg dry body weight and a temperature of 37 degrees C. Ultrafiltration was kept constant in each patient. Blood pressure (mean, systolic [SBP], and diastolic blood pressure [DBP]), pulse rate, arterial and venous temperature, energy transfer, and relative blood volume were measured at 15-minute intervals. Cardiac output, total peripheral resistance, stroke volume, and iCa were measured hourly. The 2 treatments were matched with the exception of iCa concentration. RESULTS: A significant intratreatment reduction in cardiac output and stroke volume was shown to the same extent for both groups. Intertreatment comparisons showed a significantly lower mean arterial pressure, SBP, DBP, and total peripheral resistance in the L-HF compared with the H-HF group. CONCLUSION: iCa concentration of 3.5 versus 2.5. mEq/L (1.75 versus 1.25 mmol/L) in the infusate during predilution HF stabilized blood pressure, possibly because of greater peripheral resistance rather than through changes in cardiac performance Udgivelsesdato: 2005/9

The pharmacokinetics of recombinant human erythropoietin (RhEPO) were investigated after subcutaneous (s.c.) injection in the thigh and in the abdominal wall. Eleven healthy subjects, age 24.4 years (median), were studied. Each subject received two s.c. injections of 100 U·kg-1 RhEPO dissolved in 1 ml water: one injection in the thigh and another in the abdomen. Serum erythropoietin was measured regularly by radioimmunoassay until 144 h after each injection. The mean residence time was significantly longer after injection in the thigh than in the abdomen (32.7 vs 26.2 h). The estimated half-life of absorption was significantly longer after injection in the thigh than after abdominal application (14.9 vs 12.3 h). The estimated half-life of elimination was not significantly different (4.4 vs 4.8 h). The relative difference in the area under the curve between injection in the abdomen and the thigh in the same subject ranged from -36% to +68% but there was no significant difference in bioavailability. The peak concentration was not significantly different and appeared at around 10 h (Cmax thigh, 175 U·l-1 vs Cmax abdomen, 216 U·l-1). A twin-peak configuration of the concentration vs time curve with a significant second peak at 24 h was found after injection in the thigh but not after abdominal injection. In conclusion, the mean residence time was longer after administration in the thigh, probably due to delayed absorption, but bioavailability was not significantly different. Following injection in the thigh the concentration curve had two peaks. The differences may be due to regional variations in lymph flow and to physical activity. The overall differences in pharmacokinetics appeared to be too small to recommend a general preference of the injection site.

One hundred and six renal transplant patients were studied. During the first 12 months after renal transplantation all patients were treated with cyclosporine (Cy) and prednisone. At 12 months after transplantation the patients were randomly allocated to either conventional treatment with azathioprine (Az) and prednisone (group Az) or to continued treatment with Cy and prednisone (group Cy). Serum erythropoietin (s-EPO), glomerular filtration rate (GFR) and hematocrit (Hct) were measured at 12, 18 and 24 months after transplantation. s-EPO rose in the group Az from 19 U/l (mean) at 12 months to 28 U/l (p0.01) at 18 months and remained elevated at 24 months at 29 U/l compared with baseline level and with healthy subjects without anemia 18 U/l (p0.01). There was no significant change in s-EPO in group Cy during the study. The Hct in the two groups was not significantly different. GFR was the same in the two groups at 12 months and after 24 months. In conclusion, a switch from Cy to Az 1 year after renal transplantation results in a sustained rise in s-EPO which may in part represent a compensatory phenomenon to bone marrow suppression.

Blood pressure (BP), plasma renin concentration (PRC), and 99mTc-labeled diethylenetriaminepenta acetate (DTPA) renography with determination of single kidney 99mTc-DTPA clearance and parenchymal mean transit time (MTT) were measured in exactly the same way on two consecutive days in 14 patients with renovascular hypertension (RVH), unilateral renal artery stenosis in nine and bilateral stenosis in five, and ten patients with essential hypertension (EH). The examination on day 1 served as a control for day 2 during which captopril (25 mg) was given orally one hour before measurements of PRC and DTPA clearance. Blood pressure was reduced by captopril in both groups, but the maximum decrease in systolic BP was slightly more pronounced (P less than .01) in RVH (22%, median) than EH (13%). Plasma renin concentration increased to a much greater extent (P less than .01) after captopril in RVH (366%) than in EH (46%), Single kidney 99mTc-DTPA clearance was significantly (P less than .01) reduced (-39.5%) and MTT considerably prolonged (170%) on the affected/most affected side in RVH, but both parameters were only slightly changed or unchanged on the unaffected/least affected side (-6.5%, -2% respectively) and were not significantly changed in any of the sides in EH. The degree of renal artery stenosis was significantly correlated to the increase in PRC (rho = -0.786, n = 14 patients, P less than .01), to the reduction in single kidney 99mTc-DTPA clearance (rho = 0.729, n = 19 kidneys, P less than .01) and to the prolongation in MTT (rho = -0.785, n = 16 kidneys, P less than .01). By analysis of the captopril-induced changes in 99mTc-DTPA clearance and MTT, it was possible to predict the existence of a moderate to several renal artery stenosis in arterial hypertension with a very high degree of probability, and the use of changes in 99mTc-DTPA clearance and MTT after angiotensin-converting enzyme (ACE) inhibition may become a valuable tool in differentiation between RVH and EH.