Differences in Cardiac Troponin T Composition in Myocardial Infarction and End-Stage Renal Disease Patients: A Blood Tube Effect?

BACKGROUND: Cardiac troponin T (cTnT) is key in diagnosing myocardial infarction (MI) but is also elevated in end-stage renal disease (ESRD) patients. Specific larger cTnT proteoforms were identified for the acute phase of MI, while in serum of ESRD patients solely small cTnT fragments were found. However, others allocated this to a pre-analytic effect due to abundant thrombin generation in serum. Therefore, we investigated the effect of various anticoagulation methods on cTnT composition and concentration and compared the cTnT composition of MI and ESRD patients. METHODS: The agreement of cTnT concentrations between simultaneously collected serum, lithium-heparin (LH) plasma, and ethylenediaminetetraacetic acid (EDTA) plasma was studied using the high-sensitivity (hs-)cTnT immunoassay. cTnT proteoform composition was investigated in a standardized time-dependent manner through spike experiments and in simultaneously collected blood matrixes of MI and ESRD patients. RESULTS: Excellent hs-cTnT concentration agreements were observed across all blood matrixes (slopes > 0.98; 95% CI, 0.96-1.04). Time-dependent degradation (40 kDa intact:29 kDa fragment:15 to 18 kDa fragments) was found in LH plasma and EDTA plasma, and serum in ratios (%) of 90:10:0, 0:5:95, and 0:0:100, respectively (48 h after blood collection). Moreover, gel filtration chromatography (GFC) profiles illustrated mainly larger cTnT proteoforms in MI patients, while in ESRD patients mainly 15 to 18 kDa fragments were found for all matrices. CONCLUSIONS: The extent of cTnT degradation in vitro is dependent on the (anti)coagulation method, without impacting hs-cTnT concentrations. Furthermore, mainly larger cTnT proteoforms were present in MI patients, while in ESRD patients mainly small 15 to 18 kDa cTnT fragments were found. These insights are essential when developing a novel hs-cTnT assay targeting larger cTnT proteoforms.

Educational level and gender are associated with emotional well-being in a cohort of Dutch dialysis patients.

BACKGROUND: Patients undergoing dialysis have an impaired health-related quality of life (HRQOL). There are conflicting data from small series on whether patient-related factors such as educational level have an impact on experienced HRQOL. The aim of this study was to investigate the association between educational level and HRQOL in dialysis patients. METHODS: In a single-center retrospective cross-sectional study HRQOL was measured using the Kidney Disease Quality of Life Short Form-36 (KDQOL-SF36) in prevalent chronic dialysis patients. Educational level was categorized into low, intermediate and high subgroups. Univariate and multivariate regression analyses were performed to assess the effects of age, gender, ethnicity, and dialysis vintage on the association between HRQOL and educational level. RESULTS: One hundred twenty-nine chronic dialysis patients were included. Patients with an intermediate educational level had significantly higher odds of a higher emotional well-being than patients with a low educational level 4.37 (1.-89-10.13). A similar trend was found for a high educational level (OR 4.13 (1.04-16.42), p = 0.044) The odds for women compared to men were 2.83 (1.32-6.06) for better general health and 2.59 (1.15-5,84) for emotional well-being. There was no interaction between gender and educational level for both subdomains. Each year of increasing age significantly decreased physical functioning (OR 0.94 (0.91-0.97)). CONCLUSIONS: Educational level and sex were associated with emotional well-being, since patients with intermediate and high educational level and females had better emotional well-being in comparison to patients with low educational level and males. Physical functioning decreased with increasing age.

Nivolumab exposure in a hemodialysis patient with metastatic melanoma.

The effect of intermittent hemodialysis (IHD) on nivolumab serum concentrations in patients with severe renal impairment is largely unknown. Here, we present a 79-year-old patient with metastatic melanoma and end-stage renal disease on IHD three times a week, treated with 480 mg nivolumab every 4 weeks. A serum trough concentration of nivolumab was determined before the start of the third cycle, and two samples were taken immediately before and after a hemodialysis session during this cycle. All nivolumab serum concentrations were within a similar range as those previously measured among patients without renal insufficiency, after a comparable duration of nivolumab treatment. Therefore, we conclude that IHD does not influence nivolumab exposure. Furthermore, nivolumab treatment was continued without complications and appears to be well tolerated for patients on IHD.

[Endovascular arteriovenous fistulas: percutaneous creation of vascular access for hemodialysis]. / Endovasculair aangelegde arterioveneuze fistels.

A novel endovascular technique allows percutaneous creation of arteriovenous fistulas for hemodialysis. The proximal radial artery is cannulated through the perforating vein in the cubital fossa using ultrasound guidance. A fused anastomosis between these blood vessels is created using heat and pressure. This results in an arteriovenous fistula that can be regarded as an alternative for a surgically created brachiocephalic fistula. In our early experience, this new technique is safe and successful. Moreover, no complications due to high-flow fistulas have been reported with this technique to date. Nevertheless, the intervention rate and the cost effectiveness of the new endovascular technique need to be compared to traditional open surgery before it can be considered standard clinical care.

Variación biológica de Creatinina, Cistatina C y Tasa de Filtrado Glomerular Estimada a lo largo de 24 horas / Biological Variation of Creatinine, Cystatin C, and Estimated Glomerular Filtration Rate over 24 hours

Antecedentes: La tasa de filtración glomerular estimada (TFGe) es ampliamente utilizada en la práctica clínica. El presente estudio evaluó la variación biológica intraindividual (CVI) de diferentes ecuaciones de TFGe en sujetos con enfermedad renal crónica (ERC) y sin ERC. Los objetivos de este estudio fueron (a) determinar los perfiles de variación biológica durante 24 horas de creatinina, cistatina C y TFGe y (b) determinar si el CVI de la creatinina, la cistatina C y la TFGe cambia el deterioro de la filtración glomerular. Métodos: Se analizaron muestras de sangre cada hora de 37 individuos (17 sin ERC, 20 con ERC) durante 24 h. La creatinina (método enzimático) y la cistatina C se midieron usando un Cobas 8000 (Roche Diagnostics). La TFGe se estimó utilizando la Modificación de la Dieta en la Enfermedad Renal y la Colaboración de Epidemiología de la Enfermedad Renal Crónica basada en creatinina y/o cistatina C. Las muestras de plasma se almacenaron a -80 °C antes del análisis. Se verificaron los análisis de valores atípicos y de homogeneidad antes de realizar un ANOVA anidado para determinar la variación biológica. Resultados: La CVI de creatinina fue más alta en sujetos sin ERC que en aquellos con ERC (6.4% frente a 2.5%) debido principalmente al efecto más marcado del consumo de carne sobre la variabilidad de creatinina en individuos con concentraciones iniciales de creatinina más bajas. A diferencia de la creatinina, las concentraciones de cistatina C no se vieron afectadas por el consumo de carne. La cistatina C mostró alguna variación rítmica diurna y menor en los sujetos con ERC. Los valores de referencia del cambio (VCR) de todas las ecuaciones de TFGe estuvieron dentro del 13% al 20% en ambos grupos de estudio. Conclusiones: A pesar de las diferencias en el CVI de la creatinina, el CVI y el VRC de las ecuaciones de TFGe fueron relativamente similares para los sujetos con o sin ERC.

Background: Estimated glomerular filtration rate (eGFR) is widely used in clinical practice. This study assessed the within-subject biological variation (CVI) of different eGFR equations in people with chronic kidney disease (CKD) and people without CKD. The aims of this study were (a) to determine the 24-h biological variation profiles of creatinine, cystatin C, and eGFR and (b) to determine whether CVI of creatinine, cystatin C, and eGFR changes on deterioration of glomerular filtration. Methods: Hourly blood samples were analyzed from 37 individuals (17 without CKD, 20 with CKD) during 24 h. Creatinine (enzymatic method) and cystatin C were measured using a Cobas 8000 (Roche Diagnostics). eGFR was estimated using the Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration based on creatinine and/or cystatin C. Plasma samples were stored at -80 °C before analysis. Outlier and homogeneity analyses were checked before performing a nested ANOVA to determine biological variation. Results: CVI of creatinine was higher in people without CKD than in those with CKD (6.4% vs. 2.5%) owing primarily to the more profound effect of meat consumption on creatinine variability in individuals with lower baseline creatinine concentrations. Unlike creatinine, cystatin C concentrations were unaffected by meat consumption. Cystatin C showed some diurnal rhythmic variation and less in people with CKD. Reference change values (RCVs) of all eGFR equations were within 13% to 20% in both study groups. Conclusions: Despite differences in CVI of creatinine, the CVI and RCV of the eGFR equations were relatively similar for people with or without CKD.

Randomized Controlled Trial Comparing Open Versus Laparoscopic Placement of a Peritoneal Dialysis Catheter and Outcomes: The CAPD I Trial.

OBJECTIVE: To determine the best operation technique, open versus laparoscopic, for insertion of a peritoneal dialysis (PD) catheter with regard to clinical success. Clinical success was defined as an adequate function of the catheter 2 - 4 weeks after insertion. METHODS: All patients with end-stage renal disease who were suitable for PD and gave informed consent were randomized for either open surgery or laparoscopic surgery. A previous laparotomy was not considered an exclusion criterion. Laparoscopic placement had the advantage of pre-peritoneal tunneling, the possibility for adhesiolysis, and placement of the catheter under direct vision. Catheter fixation techniques, omentopexy, or other adjunct procedures were not performed. Other measured parameters were in-hospital morbidity and mortality and post-operative infections. RESULTS: Between 2010 and 2016, 95 patients were randomized to this study protocol. After exclusion of 5 patients for various reasons, 44 patients received an open procedure and 46 patients a laparoscopic procedure. Gender, age, body mass index (BMI), hypertension, current hemodialysis, severe heart failure, and previous an abdominal operation were not significantly different between the groups. However, in the open surgery group, fewer patients had a previous median laparotomy compared with the laparoscopic group (6 vs 16 patients; p = 0.027). There was no statistically significant difference in mean operation time (36 ± 24 vs 38 ± 15 minutes) and hospital stay (2.1 ± 2.7 vs 3.1 ± 7.3 days) between the groups. In the open surgery group 77% of the patients had an adequate functioning catheter 2 - 4 weeks after insertion compared with 70% of patients in the laparoscopic group (p = not significant [NS]). In the open surgery group there was 1 post-operative death (2%) compared with none in the laparoscopic group (p = NS). The morbidity in both groups was low and not significantly different. In the open surgery group, 2 patients had an exit-site infection and 1 patient had a paramedian wound infection. In the laparoscopic group, 1 patient had a transient cardiac event, 1 patient had intraabdominal bleeding requiring reoperation, and 1 patient had fluid leakage that could be managed conservatively. The survival curve demonstrated a good long-term function of PD. CONCLUSION: This randomized controlled trial (RCT) comparing open vs laparoscopic placement of PD catheters demonstrates equal clinical success rates between the 2 techniques. Advanced laparoscopic techniques such as catheter fixation techniques and omentopexy might further improve clinical outcome.

Biological Variation of Creatinine, Cystatin C, and eGFR over 24 Hours.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is widely used in clinical practice. This study assessed the within-subject biological variation (CVI) of different eGFR equations in people with chronic kidney disease (CKD) and people without CKD. The aims of this study were (a) to determine the 24-h biological variation profiles of creatinine, cystatin C, and eGFR and (b) to determine whether CVI of creatinine, cystatin C, and eGFR changes on deterioration of glomerular filtration. METHODS: Hourly blood samples were analyzed from 37 individuals (17 without CKD, 20 with CKD) during 24 h. Creatinine (enzymatic method) and cystatin C were measured using a Cobas 8000 (Roche Diagnostics). eGFR was estimated using the Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration based on creatinine and/or cystatin C. Plasma samples were stored at -80 °C before analysis. Outlier and homogeneity analyses were checked before performing a nested ANOVA to determine biological variation. RESULTS: CVI of creatinine was higher in people without CKD than in those with CKD (6.4% vs 2.5%) owing primarily to the more profound effect of meat consumption on creatinine variability in individuals with lower baseline creatinine concentrations. Unlike creatinine, cystatin C concentrations were unaffected by meat consumption. Cystatin C showed some diurnal rhythmic variation and less in people with CKD. Reference change values (RCVs) of all eGFR equations were within 13% to 20% in both study groups. CONCLUSIONS: Despite differences in CVI of creatinine, the CVI and RCV of the eGFR equations were relatively similar for people with or without CKD.

Peritoneal dialysis in centenarian patients: no age limitation?

BACKGROUND: The majority of dialysis patients are elderly, and the trend towards even more elderly people with end-stage renal disease (ESRD) will further determine the dialysis field in the future. METHOD: If these elderly ESRD patients do not opt for conservative ESRD care, they may still qualify for peritoneal dialysis (PD), which may be assisted or unassisted. RESULTS: Although they may be more frail and have a greater co-morbidity burden compared to their younger counterparts, elderly patients with ESRD may still be able to maintain a good functionality level with adequate quality of life by performing PD, which may be assisted (treatment performed or supported e.g. by partner or nurse) or unassisted (without support). PD may indeed further contribute to maintaining autonomy, and enhance quality of life compared to in-center conventional hemodialysis. In order to illustrate this strategy, we hereby describe a centenarian patient with ESRD who received assisted PD successfully. CONCLUSIONS: With appropriate management and infrastructure, (very) high age is not a contra-indication for PD.