Intradialytic techniques for automatic and everyday access monitoring.

Vascular access dysfunction is associated with reduced delivery of dialysis, unplanned admissions, patient symptoms, and loss of access, making assessment of vascular access a fundamental part of routine care in dialysis. Clinical trials to predict the risk of access thrombosis based on accepted reference methods of access performance have been disappointing. Reference methods are time-consuming, affect the delivery of dialysis, and therefore cannot repeatedly be used with every dialysis session. There is now a new focus on data continuously and regularly collected with every dialysis treatment, directly or indirectly associated with access function, and without interrupting or affecting the delivered dose of dialysis. This narrative review will focus on techniques that can be used continuously or intermittently during dialysis, taking advantage of methods integrated into the dialysis machine and which do not affect the delivery of dialysis. Examples include extracorporeal blood flow, dynamic line pressures, effective clearance, dose of delivered dialysis, and recirculation which are all routinely measured on most modern dialysis machines. Integrated information collected throughout every dialysis session and analyzed by expert systems and machine learning has the potential to improve the identification of accesses at risk of thrombosis.

Effluent microscopy is a useful adjuvant diagnostic tool in peritoneal dialysis-associated peritonitis.

BACKGROUND: Infectious complications are the leading cause of technical failure in peritoneal dialysis (PD); however, targeted anti-infective therapy is not feasible at the onset, as effluent cultures take days and may be inconclusive. Although recommended by the guidelines, divergent positivity rates of Gram-stained effluent microscopy question the value of its usefulness. This study aimed to evaluate if microscopy of cell types serves as an additional and timely diagnostic approach. MATERIALS AND METHODS: This single-center retrospective analysis included prevalent PD patients (n = 250) between 2007 and 2017. Automated quantitative cell count, cytological analysis of Hemacolor and Gram-stained effluent sediment, and effluent cultures were conducted during peritonitis episodes. We calculated the rate of peritonitis, positivity rate of effluent cultures, and effluent microscopy. RESULTS: There were 155 at-risk cases of peritonitis in 662.7 years during the observation period. The culture positivity rate was 73.5%. In neutrophilic culture-negative peritonitis (CNP), effluent Gram staining yielded the identification of the microbial species in 51.6% cases. In 24.4% of CNP, effluent microscopy showed eosinophilic peritonitis, which occurred with less initial effluent leucocytes and showed better PD survival. CONCLUSION: In PD-associated peritonitis, Gram-stained dialysate with effluent microscopy supplements culture results in CNP. Hemacolor staining is crucial for differentiating eosinophilic peritonitis, showing a divergent clinical course and outcome.

A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health.

In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal health. In a double-blinded, randomized crossover design, stable PD patients were treated with AlaGln (8 mM) or placebo added to PD fluid for eight weeks. As primary outcome measures, dialysate cancer-antigen 125 (CA-125) appearance rate and ex vivo stimulated interleukin-6 (IL-6) release were assessed in peritoneal equilibration tests. In 8 Austrian centers, 54 patients were screened, 50 randomized, and 41 included in the full analysis set. AlaGln supplementation significantly increased CA-125 appearance rate and ex vivo stimulated IL-6 release. AlaGln supplementation also reduced peritoneal protein loss, increased ex vivo stimulated tumor necrosis factor (TNF)-α release, and reduced systemic IL-8 levels. No adverse safety signals were observed. All 4 peritonitis episodes occurred during standard PD fluid treatment. A novel AlaGln-supplemented PD fluid improves biomarkers of peritoneal membrane integrity, immune competence, and systemic inflammation compared to unsupplemented PD fluid with neutral pH and low-glucose degradation. A phase 3 trial is needed to determine the impact of AlaGln supplementation on hard clinical outcomes.

Loss of antimicrobial effect of trisodium citrate due to 'lock' spillage from haemodialysis catheters.

BACKGROUND: Due to its reported antimicrobial effects, hypertonic citrate (46.7%) is a widely used catheter lock solution, but following instillation, citrate inevitably spills into the systemic circulation. This process is mainly driven by hydraulic effects during instillation and density differences between blood and lock solution. Hence, in haemodialysis catheters, intra-luminal citrate concentration ranges from 0% (at the tip in catheters with side holes), 3% (between the side holes and the highest point of the catheter) to 46.7% (at the Luer end) with possible differences in antimicrobial effects. We investigated in vitro the antimicrobial effect of pure citrate 46.7%, citrate 46.7% diluted with saline and blood to a net concentration of 3% (=citrate 3%), and of citrate-free blood, simulating in vivo conditions in different catheter sections. METHODS: Time-kill studies measuring the antimicrobial effect of citrate 46.7%, citrate 3% and citrate-free blood were performed with overnight cultures of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). RESULTS: Citrate 46.7% reduced the number of E. coli by 2 log units but after 24 h, 10(6) CFU/mL were still present. Citrate 3% and citrate-free blood had no antimicrobial effect on E. coli. Citrate 46.7%, citrate 3% and citrate-free blood had scarce antimicrobial effect on S. aureus within 24 h. CONCLUSIONS: Spillage of catheter lock solution leading to reduced intra-luminal citrate concentrations considerably reduces the antimicrobial effect of citrate 46.7% on E. coli. As none of the solutions tested had relevant antimicrobial effect on S. aureus, the antimicrobial effect of 46.7% citrate lock solution in vivo has to be seriously questioned.

Prevalence of detectable venous pressure drops expected with venous needle dislodgement.

Venous needle dislodgement (VND) is a potentially fatal complication during hemodialysis (HD) treatment and the venous pressure monitor is the most widely used device for its detection. VND can only be detected by the venous sensor if the resulting pressure drop exceeds the difference between the actual venous pressure and the lower alarm limit. In clinical practice, the lower alarm limit is usually set 30-40 mmHg below the actual venous pressure to avoid a disproportionate high number of nuisance alarms. The aim of this study was to quantify the number of fistulas and grafts in a group of HD patients where venous pressure monitoring can be expected to detect VND. We determined intra-access pressures in 99 chronic HD patients. Sixty-five (65.7%) had a fistula and 34 (34.3%) had a prosthetic graft as a vascular access. Mean intra-access pressure (Pa ) in fistulas was 32.6 ± 23.5 mmHg, whereas in grafts mean Pa was 60.9 ± 19.5 mmHg. Nineteen (29.2%) of the fistulas and 32 (94.1%) of the grafts exhibited an intra-access pressure above 40 mmHg. Therefore, in our study nearly all grafts but only 29% of fistulas would fulfill the requirement for venous pressure monitoring to detect VND.

Microbiological screening for earlier detection of central venous catheter-related bloodstream infections.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are currently detected with a reactive diagnostic policy, that is, application of tests to patients with clinically suspected CRBSI. The aim of our study was to evaluate whether CRBSIs could be anticipated in an earlier stage by microbiological screening using peptide nucleic acid fluorescence in situ hybridization (PNA FISH) with universal hybridization probes or acridine-orange leucocyte cytospin (AOLC) tests in haemodialysis and haematological patients with CVCs in situ compared with routine test. MATERIALS AND METHODS: Peptide nucleic acid fluorescence in situ hybridization (PNA FISH) and AOLC tests using blood samples from both CVC lines in patients undergoing haemodialysis were performed three times a week and from one CVC line in haematological patients were performed daily. Results were compared with those obtained from routinely performed CRBSI diagnostic tests. RESULTS: One hundred fifteen patients with 139 catheter periods were investigated. The mean observation time per catheter period was 25 days (IQR 13.5-43.5), resulting in 5615 CVC days with a total of 4839 tested blood samples. Five CRBSI cases were detected by routine measures resulting in a CRBSI rate of 0.9/1000 catheter days. Four of five CRBSIs could be anticipated by positive PNA FISH and AOLC tests 2-8 days before the diagnosis was established with routine measures. CONCLUSIONS: The proactive anticipative strategy using microscopic examination of CVC blood samples to anticipate CRBSI in an earlier stage compared with routine measures is a new diagnostic approach in patients with CVCs and a high risk of developing CRBSI.

Volume excess in chronic haemodialysis patients--effects of treatment frequency and treatment spacing.

BACKGROUND: The main objective of this study was to theoretically quantify the fluctuations of fluid volume excess for different modes of intermittent ultrafiltration schedules and to compare the prediction for the typical and asymmetric thrice-weekly schedule to clinical, physiological and biophysical markers of volume expansion in a group of stable haemodialysis patients. METHODS: Overall volume excess (V(OVE)) was described as the sum of a time-independent (V(0)) and a time-dependent component (V). An exact relationship was developed to relate V to variable treatment frequency, treatment spacing and net volume accumulation rate. In a single-centre haemodialysis population, body mass profiling was combined with volume state evaluation by bioimpedance analysis, N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels, clinical signs, a volume questionnaire and blood pressure levels. RESULTS: In 23 patients following the typical thrice-weekly schedule, the time-averaged volume excess (V) during the whole week (1.1 ± 0.5 L) was significantly larger than that during the midweek interval (0.9 ± 0.4 L) (P < 0.002) by a factor comparable to that of 1.21 obtained from the theoretical analysis. V(OVE) was 1.3 ± 1.7 L and significantly related to pre- (P < 0.001) and post-dialysis levels of NT-pro BNP (P < 0.001). CONCLUSION: Asymmetric treatment spacing such as with the typical thrice-weekly treatment schedule leads to a significant increase in time-averaged volume excess. The theoretical analysis allows for comparison of time-averaged volume excess in treatments varying with regard to treatment frequency and regularity and could be helpful to prescribe post-treatment volume (target weight) for such variable treatment modes.

Trisodium citrate induced protein precipitation in haemodialysis catheters might cause pulmonary embolism.

BACKGROUND: The locking anticoagulant plays a decisive role in the patency of central venous catheters (CVCs) used for haemodialysis. During injection, the hydraulic effects inevitably cause lock solution to spill into the systemic circulation. Density differences between whole blood (WB) and the lock solution cause further gravity-induced seepage of lock solution. This is followed by an influx of WB into the catheter, also described for trisodium citrate, which is a common agent for serum protein precipitation. Embolic complications from haemodialysis catheters locked with hypertonic trisodium citrate have been reported. We aimed to investigate protein precipitation in trisodium citrate locked catheters as a possible cause of pulmonary embolisms. METHODS: In vitro, WB and trisodium citrate (concentrations ranging from 4.7 to 46.7%) mixtures in a ratio of 1:4 were used to assess protein precipitation. Additionally, WB/trisodium citrate mixture was pumped through a 20-µm mesh filter, simulating pulmonary vessels, and filtrate pressure was measured. In vivo, listed filling volumes of haemodialysis catheters locked with trisodium citrate 4% (n=10), 10% (n=10), 20% (n=10) or 46.7% (n=10) were aspirated and then analysed for protein precipitation. RESULTS: In vitro, protein precipitation capable of causing filter occlusion was observed in test solutions containing trisodium citrate above a concentration of 12%. In vivo, protein precipitation was detected in all samples from the CVCs filled with trisodium citrate 46.7% (n=10) and 20% (n=10). In contrast, there were no signs of precipitation in samples from the catheters filled with trisodium citrate 4% (n=10) or 10% (n=10). CONCLUSIONS: Our in vitro results demonstrate that protein precipitates inside haemodialysis catheters when trisodium citrate is used above the concentrations of 12%. Precipitated protein may have contributed to the pathophysiology of reported embolisms from haemodialysis catheters filled with hypertonic trisodium citrate. Based on our findings, we suggest that trisodium citrate lock solution up to the concentration of 10% can be used safely.

Bioimpedance-based volume at clinical target weight is contracted in hemodialysis patients with a high body mass index.

OBJECTIVE: To compare volume overload in stable hemodialysis (HD) patients assessed by standard clinical judgment with data obtained from bioimpedance analysis. METHODS: Ultrafiltration volume (VU) was delivered as prescribed by standard clinical practice. Independently, a measure for volume overload was assessed by a clinical score (SW). The Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany) was used to derive values for extracellular volume (VE) and volume overload (VO) before HD. Arterial pressures (P0, P1) and serum levels of NT-pro-BNP (B0, B1) were evaluated before and after HD. RESULTS: In 28 patients (11 women, age: 51.3 ± 13.3 y, body mass index (BMI) 18.5 - 40.9 kg/m2; VE: 17.91 ± 3.45 l) delivered VU was 2.41 ± 1.03 l and not different from VO of 2.08 ± 1.49 l derived from bioimpedance analysis. There was no correlation between VO and VU (r = -0.15, p = 0.46) but a negative correlation between the difference VO - VU (i.e., the volume overload at treatment end) and BMI (r = -0.49, p < 0.01). Positive correlations were observed between B0 and the relative volume overload (= VO/VE) (r = 0.58, p < 0.001). CONCLUSION: The well recognized relationship between cardiac natriuretic peptides and volume expansion was confirmed. The volume overload at treatment end (VO - VU) was negligible for the whole group of patients but more negative with increasing BMI. It therefore appears that in comparison to bioimpedance-based evaluation the clinical judgment overestimates volume overload in obese patients which leads to the delivery of high ultrafiltration volumes and to volume contraction at the end of a dialysis session in this group of patients.

Development of an Architecture to Implement Machine Learning Based Risk Prediction in Clinical Routine: A Service-Oriented Approach.

BACKGROUND: Patients at risk of developing a disease have to be identified at an early stage to enable prevention. One way of early detection is the use of machine learning based prediction models trained on electronic health records. OBJECTIVES: The aim of this project was to develop a software solution to predict cardiovascular and nephrological events using machine learning models. In addition, a risk verification interface for health care professionals was established. METHODS: In order to meet the requirements, different tools were analysed. Based on this, a software architecture was created, which was designed to be as modular as possible. RESULTS: A software was realised that is able to automatically calculate and display risks using machine learning models. Furthermore, predictions can be verified via an interface adapted to the need of health care professionals, which shows data required for prediction. CONCLUSION: Due to the modularised software architecture and the status-based calculation process, different technologies could be applied. This facilitates the installation of the software at multiple health care providers, for which adjustments need to be carried out at one part of the software only.

Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL) may improve renal outcome of acute contrast media induced nephropathy: a randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study).

BACKGROUND: Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase-associated lipocalin (NGAL), a new biomarker predictive for acute kidney injury (AKI), has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration. METHODS/DESIGN: The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM) application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death.We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the treatment arm if 1200 patients are recruited into the study. DISCUSSION: A volume expansion strategy showing a benefit from earlier intervention for patients with markedly elevated urinary NGAL values, indicating a CIN, might arise from data from this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01292317.

Supine equilibration of extracellular fluid in peritoneal dialysis varies with intra-abdominal pressure.

BACKGROUND: Increased intra-abdominal pressure (PIA) leads to venous congestion in splanchnic and adjoining circulations. The aim is to examine whether PIA in peritoneal dialysis (PD) affects the mobilization of extracellular fluid from the lower body in supine body position. METHODS: Patients were studied during a regular peritoneal equilibration test (PET) in supine body position using multifrequency bioimpedance analysis to determine extracellular resistance and absolute volume overload (AVO) in wrist-to-ankle (W2A) as well as in ankle-to-ankle (A2A) configurations. Measurements were taken at baseline (T0) after draining the peritoneal cavity, at T1 shortly after filling with 2 L of standard dialysate, and at T2 before taking the 2 h PET samples. PIA was measured from the column height in the PD catheter. Extracellular resistance in the lower extremities (RL) was taken as half of the A2A resistance. RESULTS: Eighteen patients (56 ± 15 years, 76 ± 21 kg, body mass index (BMI) 26.4 ± 7 kg/m2, 13 men) were studied. After having assumed a supine body position for the duration of 17, 77, and 155 min, AVO continuously decreased from 1.6 ± 1.3 (T0) to 1.2 ± 1.5 (T1) and 1.0 ± 1.4 L (T2). RL significantly increased from 238 ± 57 (T0) to 254 ± 62 (T1) and 264 ± 67 Ohm (T2). This increase was negatively correlated to BMI and PIA measured at any time point, but not to net ultrafiltration volume. CONCLUSIONS: Orthostatic fluid shifts from the lower limbs may take up to 2 h in supine PD patients, especially with high BMI and PIA because of venous congestion in splanchnic and adjoining circulations.

Contrast Induced Acute Kidney Injury and its Impact on Mid-Term Kidney Function, Cardiovascular Events and Mortality.

The existence and clinical relevance of contrast induced acute kidney injury (CI-AKI) is still heavily debated and angiographic procedures are often withheld in fear of CI-AKI, especially in CKD-patients. We investigated the incidence of CI-AKI in cardiovascular high risk patients undergoing intra-arterial angiography and its impact on mid-term kidney function, cardiovascular events and mortality. We conducted a prospective observational trial on patients undergoing planned intra-arterial angiographic procedures. All subjects received standardized intravenous hydration prior to contrast application. CI-AKI was defined according to a ≥25% increase of creatinine from baseline to either 24hrs or 48hrs after angiography. Plasma creatinine and eGFR were recorded from the institutional medical record system one and three months after hospital discharge. Patients were followed up for two years to investigate the long term effects of CI-AKI on cardiovascular events and mortality. We studied 706 (317 female) patients with a mean eGFR of 52.0 ± 15 ml·min-1·1.73 m-2. The incidence of CI-AKI was 10.2% (72 patients). In 94 (13.3%) patients serum creatinine decreased ≥25% either 24 or 48 hours after angiography. Patients with CI-AKI had a lower creatinine and a higher eGFR at baseline, but no other independent predictors of CI-AKI could be identified. Kidney function was not different between both groups one and three months after discharge. After a two year follow up the overall incidence of cardiovascular events was 56.5% in the CI-AKI group and 58.8% in the Non CI-AKI group (p = 0.8), the incidence of myocardial infarctions, however, was higher in CI-AKI-patients. Overall survival was also not different between patients with CI-AKI (88.6%) and without CI-AKI (84.7%, p = 0.48). The occurrence of CI-AKI did not have any negative impact on mid-term kidney function, the incidence of cardiovascular events and mortality. Considerable fluctuations of serum creatinine interfere with the presumed diagnosis of CI-AKI. Necessary angiographic procedures should not be withheld in fear of CI-AKI.

Author Correction: Structural and functional differences in gut microbiome composition in patients undergoing haemodialysis or peritoneal dialysis.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Structural and functional differences in gut microbiome composition in patients undergoing haemodialysis or peritoneal dialysis.

Complications of end-stage renal disease (ESRD) are critically related to inflammation. The gut microbiome is a key driver of inflammation. Since dialysis modalities may differently influence the gut microbiome, we aimed to compare the effects of haemodialysis (HD) and peritoneal dialysis (PD) on patients' gut microbiome composition and function. We therefore studied faecal microbiome composition and function as well as inflammation and gut permeability in 30 patients with ESRD (15 HD, 15 PD) and compared to 21 healthy controls. We found an increase in potentially pathogenic species and a decrease in beneficial species in patients on HD and to a lesser extend in patients on PD when compared to controls. These changes in taxonomic composition also resulted in differences in predicted metagenome functions of the faecal microbiome. In HD but not in PD, changes in microbiome composition were associated with an increase in c-reactive protein (CRP) but not with intestinal inflammation or gut permeability. In conclusion microbiome composition in ESRD differs from healthy controls but also between modes of dialysis. These differences are associated with systemic inflammation and cannot completely be explained by dialysis vintage. The mode of renal replacement therapy seems to be an important driver of dysbiosis in ESRD.

Neutrophil gelatinase-associated lipocalin (NGAL) fails as an early predictor of contrast induced nephropathy in chronic kidney disease (ANTI-CI-AKI study).

The aim of the study was to evaluate the diagnostic accuracy of urinary neutrophil gelatinase- associated lipocalin (uNGAL) in patients with chronic kidney disease (CKD) as an early biomarker for contrast induced acute kidney injury (CI-AKI) and to investigate whether patients with an uNGAL increase might benefit from an additional intravenous volume expansion with regard to CI-AKI-incidence. We performed a prospective randomized controlled trial in 617 CKD-patients undergoing intra-arterial angiography. Urinary NGAL was measured the day before and 4-6hrs after angiography. In the event of a significant rise of uNGAL patients were randomized either into Group A, who received intravenous saline post procedure or Group B, who did not receive post-procedural i.v. fluids. Ten patients (1.62%) exhibited a significant rise of uNGAL after angiography and were randomized of whom one developed a CI-AKI. In the entire cohort the incidence of CI-AKI was 9.4% (58 patients) resulting in a specificity of 98.4% (95% CI: 97.0-99.3%) and a sensitivity of 1.72% (95% CI: 0.044-9.2%) of uNGAL for the diagnosis of CI-AKI. In this study uNGAL failed to predict CI-AKI and was an inadequate triage tool to guide an early intervention strategy to prevent CI-AKI. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01292317.