Optical Online Monitoring of Uremic Toxins beyond Urea

This chapter presents origin and physical basis of the optical method for traditional haemodialysis (HD) dose assessment, accepted as a valid bloodless, robust, automatic, in situ and online monitoring technology in clinical praxis. Dialysis dose Kt/V, total removed urea (TRU) and the nutrition parameters PCR, nPCR estimation from ultraviolet (UV) absorbance in the spent dialysate is explained. Since urea, a small water-soluble uremic solute and a surrogate marker for the efficiency of dialysis treatment to clear the blood of toxins and metabolic end products, is not representative for all retained uremic toxins removed with the modern dialysis care, new developments of optical online monitoring of uremic toxins, beyond urea, are discussed. Optical intradialytic monitoring of small-, middle- and protein-bound molecules’ removal, exemplified by marker molecules uric acid, beta-2 microglobulin and indoxyl sulphate, is described. A new concept and sensor technology for multi-component uremic toxins’ intradialytic optical monitoring of spent dialysate with some clinical examples are introduced. Drug interference studies during the optical dialysis monitoring and future directions in optical monitoring are included. Offered benefits will be more patient-centred, integrated and cost-efficient care, as feedback for clinicians helps to improve and personalize the treatment quality, minimizing costly adverse effects

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Haemodialysis Treatment Monitored On-line by Ultra Violet Absorbance

This thesis describes and evaluates an optical method utilizing ultra violet (UV) absorbance for on-line monitoring of haemodialysis treatment. Increased efficiency of haemodialysis treatment is considered to correlate to decreased morbidity and mortality when urea clearance (Kt/V) is elevated. However, further improvements have not been achieved at a higher Kt/V. The mortally rate in the haemodialysis population is still high (27% in Sweden). Urea as the clinical marker is under discussion, partly due to urea being non-toxic, but also that the uraemic syndrom is the result of a cumulative retention of innumerable involved compounds. On-line monitoring systems based on urea determination for improved dialysis efficiency have been suggested and developed in different settings over the last two decades, but have not achieved worldwide utilisation as routine clinical equipment. This thesis demonstrates that the UV-technique utilising 280, 285 and 297 nm is capable of estimating dialysis efficiency in therms of Kt/V, nutritional status in terms of protein catabolic rate (PCR), with the same characteristics as existing methods. One novel finding using UV-absorbance with high sampling rates is the on-line visualisation of the clearance process for following variations in clearance caused by clinical events and disturbances as well as during and after adjustments. The fact that the UV-absorbance technique does not measure urea directly but has high correlation to several other both UV-absorbing and not-absorbing solutes makes it suitable to reflect a more overall solute retention process. Finally, a new efficiency parameter based on the calculation of the area under UV- curve (clearance curve), is suggested to reflect the total removal of some solutes. In summary the UV-technique has the potential to be an additional tool to evaluate improvements of dialysis efficiency, which may result in decreased morbidity, longer life span and enhanced quality of life for the haemodialysis patients

Cannulation technique and complications in arteriovenous fistulas : a Swedish Renal Registry-based cohort study

Background The four cannulation techniques, rope ladder (RL), area puncture (AP), buttonhole with blunt needles (BHb), and buttonhole with sharp needles (BHs), affects the arteriovenous fistula (AVF) in different ways. The aim of this study was to describe the relationship between the different cannulation techniques and the occurrence of AVF complications. Methods The study was performed as a national registry-based cohort study using data from the Swedish Renal Registry (SRR). Data were collected from January 2014 to October 2019. Seventy of Swedens dialysis units participate in the registry. We analyzed a total of 1328 AVFs in this study. The risk of complications was compared between the four different cannulation techniques. The risk of AVF complications was measured by the incidence and incidence rate ratio (IRR). We compared the IRRs of complications between different cannulation techniques. Results BHs is the most common cannulation technique in Sweden. It has been used in 55% of the AVFs at some point during their functional patency. BHb (29%), RL (13%), and AP (3%) has been used less. BHb had the lowest risk of complications compared to the other techniques, and a significantly lower risk of stenosis, infiltration, cannulation difficulties, compared to RL and BHs. Cannulation difficulties were significantly more common using AP compared to BHs, and BHb. Infections were not significantly increased using the buttonhole technique. Conclusions BHb had the lowest risk of complications. Infections were not significantly increased using the buttonhole technique. Dialysis units with a low infection rate may continue to use the buttonhole technique, as the risk of complications is lower.Funding Agencies|Region Ostergotland; Linkoping University</p

How to needle : A mixed methods study on choice of cannulation technique for arteriovenous fistula

Aims and objectives The aim of this study was to describe the basis for choosing a cannulation technique for arteriovenous fistula. Background Four cannulation techniques are relevant to cannulating an arteriovenous fistula: rope ladder, area puncture and buttonhole using blunt or sharp needles. The chosen technique may affect both the patency and number of complications. Design The study used a convergent mixed methods design and inductive approach. Methods A questionnaire and an inquiry of local guidelines were sent to nurses in all dialysis units in Sweden. Questionnaires were answered by nurses from 37 units, and 29 units included their local guidelines. The questionnaires were analysed using descriptive statistics and qualitative content analysis, and the guidelines were analysed using qualitative content analysis. The different analyses were combined in a final result. The study is based on GRAMMS guidelines. Results Local guidelines, patients and nurses own judgement, and consultation with colleagues were found to greatly influence the choice of cannulation technique. Buttonhole was the most preferred cannulation technique in the participating units and was favoured by nurses when choosing a cannulation technique. The process of choosing a cannulation technique was found to be influenced by the dedication to good cannulation technique and healthy arteriovenous fistulas, whether the technique is perceived as being easy to use and is expected to prevent complications and based on the experienced-based knowledge of each dialysis unit. Conclusions Choosing a cannulation technique is a process based on the nurse, local guidelines and the patient. Most dialysis nurses and units in Sweden consider buttonhole to be a good cannulation technique and use it as their standard technique. Relevance to clinical practice The results provide insight into why cannulation techniques are chosen differently in different units. The results also show the importance of evidence in making decisions on cannulation technique.Funding Agencies|Region Ostergotland; Swedish Research Council</p

Preconditions that facilitate cannulation in arteriovenous fistula : A mixed-methods study

Background: Nurses have a great responsibility in the daily care of arteriovenous fistulae, which entails the potential to affect patency. However, good cannulation technique involves more than placing a needle in the vessel and relies on different skills to facilitate needling. Objectives: To describe the preconditions for cannulation in arteriovenous fistulas. Design: Descriptive statistics and qualitative content analysis were used in a mixed-methods design. Participants: Haemodialysis units in Sweden. Measurements: Local guidelines regarding arteriovenous fistula cannulation were analysed in parallel with responses to a questionnaire that contained open-ended and closed-ended questions on cannulation technique. Results: Preconditions that facilitate cannulation fall into five stages, each with relevant factors in relation to the cannulation, as follows: planning cannulation-maturation and planning the cannulation, patient record, education and experience, and patient information; precannulation-physical examination, hygiene routines, arm position, tourniquet, choosing the cannulation site, and preventing pain; during cannulation-how to needle, type of needle, angle during cannulation, fixation, and adjusting; evaluating cannulation-blood flow rate and arterial and venous pressure; and postcannulation-needle withdrawal and haemostasis. The majority of dialysis units identified implementation of most of these preconditions, but the units handle several practical aspects differently. Conclusions: Tracing the chain of cannulation led to identification of necessary preconditions for facilitating good cannulation technique. The findings also show the need for a better understanding of how different preconditions affect arteriovenous fistula and patency.Funding Agencies|Region Ostergotland, Sweden; Swedish Research Council</p

Vasoactive Peptide Levels after Change of Dialysis Mode

Background/Aims: Plasma concentrations of the N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) are increased in end-stage renal disease. Improvement in hemodynamic stability has been reported when switching from hemodialysis (HD) to on-line hemodiafiltration (ol-HDF). The aim of this study was to investigate plasma concentrations of NT-proBNP, BNP and neuropeptide Y (NPY) during a 1-year follow-up, after a change from high-flux HD to postdilution ol-HDF. Additional variables were also studied, e.g. pulse wave velocity and ordinary clinical parameters. Method: We conducted a prospective, single-center study including 35 patients who were switched from HD to HDF. Plasma concentrations of NT-proBNP, BNP and NPY before and after dialysis were measured at baseline (i.e. HD) and at 1, 2, 4, 6 and 12 months on HDF. Results: All three peptide levels decreased significantly during HD and HDF when comparing concentrations before and after dialysis. Mean absolute value (before/after) and relative decrease (%) before versus after dialysis was 13.697/9.497 ng/l (31%) for NT-proBNP, 62/40 ng/ml (35%) for BNP and 664/364 pg/l (45%) for NPY. No significant differences were observed when comparing predialysis values over time. However, postdialysis NT-proBNP concentration showed a significant decrease of 48% over time after the switch to HDF. Conclusion: The postdialysis plasma levels of NT-proBNP, BNP and NPY decreased significantly during both dialysis modes when compared to before dialysis. The postdialysis lowering of NT-proBNP increased further over time after the switch to ol-HDF; the predialysis levels were unchanged, suggesting no effect on its production in the ventricles of the heart

Preference-based patient participation for most, if not all: A cross-sectional study of patient participation amongst persons with end-stage kidney disease

Background Patient participation is considered central for good healthcare. Yet, the concept is not fully understood when it comes to patients experiences of participation in conjunction with their preferences, particularly in long-term healthcare. The aim of this study was to investigate the extent and variation of preference-based patient participation in patients with end-stage kidney disease (ESKD). Methods A cross-sectional study was conducted with 346 patients in renal care. The main variables were patients preferences for and experiences of patient participation, determined using the Patient Preferences for Patient Participation tool, the 4Ps. Analyses identified the degree of match between preferences and experiences, that is, the preference-based patient participation measure. Results Overall, 57%-84% of the patients reached a sufficient level of preference-based patient participation on the items, while 2%-12% reached an insufficient level. A mismatch indicated either less or more participation than preferred; for example, 40% had less experience than preferred for taking part in planning, and 40% had more than preferred for managing treatment. Conclusion This study shows that, although many patients reach a sufficient level of preference-based patient participation, this is not the case for all patients and/or attributes. Further opportunities for a mutual understanding of patients preferences are needed for healthcare professionals to support person-centred patient participation. Patient or Public Contribution The 4Ps is manufactured in collaboration with people with experience of the patient role, and persons living with ESKD were engaged in identifying their preferences and experiences of participation in renal care.Funding Agencies|Forskningsradet i Sydostra Sverige [930678]; Njurfonden [F2018-0036]</p

Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment

Background: Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination has not been determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and immunoglobulin G (IgG) subclass distribution. We aimed to address this by characterizing the autoantibody profile in anti-GBM patients: we utilized samples from the GOOD-IDES-01 (treating GOODpastures disease with Imunoglobulin G Degrading Enzyme of Streptococcus pyogenous) ( identifier: NCT03157037) trial , where imlifidase, which cleaves all IgG in vivo within hours, was given to 15 anti-GBM patients.Methods: In the GOOD-IDES-01 trial, plasmapheresis was (re)started if anti-GBM antibodies rebounded. Serum samples were collected prospectively for 6 months and analyzed for anti-GBM epitope specificity using recombinant constructs of the E-A and E-B epitopes, IgG subclass using monoclonal antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). The results were correlated with clinical data.Results: Patients with a rebound (n = 10) tended to have lower eGFR at 6 months (11 vs 34 mL/min/1.73 m(2), P = .055), and patients with dialysis at 6 months had a higher E-B/E-A ratio at rebound (0.8 vs 0.5, P = .047). Moreover, two patients demonstrated increasing epitope restriction and several patients displayed a shift in subclass distribution at rebound. Six patients were double positive for ANCA. ANCA rebound was seen in 50% of patients; only one patient remained ANCA positive at 6 months.Conclusions: In this study, rebound of anti-GBM antibodies, especially if directed against the E-B epitope, was associated with a worse outcome. This supports the notion that all means should be used to eliminate anti-GBM antibodies. In this study ANCA was removed early and long-term by imlifidase and cyclophosphamide.Funding Agencies|Skane University Hospital Research Foundations (SUS Stiftelser och fonder); Region Skane [2020-O000028]; Region Ostergotland [LIO-755 381]; Ingrid Asp Foundation [991 602]; Hansa Biopharma [IMH-2016-00286]; Inga-Britt and Arne Lundberg Foundation [LU-2021]; Swedish Research Council; Thelma Zoegas Fund for Medical Research [91 282]</p