Assessing Tissue Hydration Dynamics Based on Water/Fat Separated MRI.

BACKGROUND: Optimal fluid status is an important issue in hemodialysis. Clinical evaluation of volume status and different diagnostic tools are used to determine hydration status in these patients. However, there is still no accurate method for this assessment. PURPOSE: To propose and evaluate relative lean water signal (LWSrel ) as a water-fat MRI-based tissue hydration measurement. STUDY TYPE: Prospective. POPULATION: A total of 16 healthy subjects (56 ± 6 years, 0 male) and 11 dialysis patients (60.3 ± 12.3 years, 9 male; dialysis time per week 15 ± 3.5 hours, dialysis duration 31.4 ± 27.9 months). FIELD STRENGTH/SEQUENCE: A 3 T; 3D spoiled gradient echo. ASSESSMENT: LWSrel , a measurement of the water concentration of tissue, was estimated from fat-referenced MR images. Segmentations of total adipose tissue as well as thigh and calf muscles were used to measure LWSrel and tissue volumes. LWSrel was compared between healthy subjects and dialysis patients, the latter before and after dialysis. Bioimpedance-based body composition monitor over hydration (BCM OH) was also measured. STATISTICAL TESTS: T-tests were used to compare differences between the healthy subjects and dialysis patients, as well as changes between before and after dialysis. Pearson correlation was calculated between MRI and non-MRI biomarkers. A P value <0.05 was considered statistically significant. RESULTS: The LWSrel in adipose tissue was significantly higher in the dialysis cohort compared with the healthy cohort (246.8% ± 60.0% vs. 100.0% ± 10.8%) and decreased significantly after dialysis (246.8 ± 60.0% vs. 233.8 ± 63.4%). Thigh and calf muscle volumes also significantly decreased by 3.78% ± 1.73% and 2.02% ± 2.50% after dialysis. There was a significant correlation between changes in adipose tissue LWSrel and ultrafiltration volume (r = 87), as well as with BCM OH (r = 0.66). DATA CONCLUSION: MRI-based LWSrel and tissue volume measurements are sensitive to tissue hydration changes occurring during dialysis. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

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 GOODpasture's disease with Imunoglobulin G Degrading Enzyme of Streptococcus pyogenous) (ClinicalTrials.gov 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 EA and EB 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 m2, P = .055), and patients with dialysis at 6 months had a higher EB/EA 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 EB 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.

Patient participation in end-stage kidney disease care: variation over time and effects of staff-directed interventions - a quasi-experimental study.

BACKGROUND: Among those elements establishing decent quality of care from a patient perspective, opportunities to participate in accord with one's individual needs and preferences are central. To date, little is known the extent of preference-based patient participation in kidney care, and what facilitates optimal conditions. This study investigated i) preference-based patient participation in kidney care over time, and ii) the effects of interventions designed to enhance person-centred patient participation. METHODS: A quasi-experimental study was conducted across nine kidney care sites in southeast Sweden. A cohort of 358 patients with stage IV chronic kidney disease (eGRF 15-19 ml/min) or V (eGRF < 15 mL/min) entered the study. Of these, 245 patients (with kidney replacement therapy or intermittent outpatient visits only) completed a survey on patient participation at four time points: every six months from August 2019 to May 2021, patients reported their preferences for and experiences of participation using the validated Patient Preferences for Patient Participation tool, the 4Ps. Between the first and second data collection points, interventions were provided for designated staff to facilitate person-centred participation, using two strategies for two subgroups at three sites each: the managers receiving a bundle of information via e-mail on patient participation in a standard dissemination procedure (three sites), or an additional half-year support program for implementation offered to 1-2 staff per site (three sites), with no intervention for a control group (three sites). The differences in 4Ps data between groups were analysed using multilevel ordinal regression. RESULTS: Over time and across all sites, most patients' experiences of participation fully or almost fully matched their engagement preferences (57%-90%). Still, up to 12% of patient reports indicated that their preferences and experiences were insufficiently matched: in these cases, the patients had preferred to be more involved than they had experienced, for example, in making healthcare plans and setting health-related goals. The interventions did not affect the levels of preference-based participation, but patients in the control group sites had slightly more consistent matches. CONCLUSIONS: Living with kidney failure necessitates patient engagement, but opportunities to participate in accordance with one's preferences are not fully provided for all patients. Additional efforts to support a common understanding and to ensure person-centred patient participation is still needed.

Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study.

BACKGROUND: The prognosis for kidney survival is poor in patients presenting with circulating anti-glomerular basement membrane (GBM) antibodies and severe kidney injury. It is unknown if treatment with an endopeptidase that cleaves circulating and kidney bound IgG can alter the prognosis. METHODS: An investigator-driven phase 2a one-arm study (EudraCT 2016-004082-39) was performed in 17 hospitals in five European countries. A single dose of 0.25 mg/kg of imlifidase was given to 15 adults with circulating anti-GBM antibodies and an eGFR <15 ml/min per 1.73m2. All patients received standard treatment with cyclophosphamide and corticosteroids, but plasma exchange only if autoantibodies rebounded. The primary outcomes were safety and dialysis independency at 6 months. RESULTS: At inclusion, ten patients were dialysis dependent and the other five had eGFR levels between 7 and 14 ml/min per 1.73m2. The median age was 61 years (range 19-77), six were women, and six were also positive for anti-neutrophil cytoplasmic antibodies. Then 6 hours after imlifidase infusion, all patients had anti-GBM antibodies levels below the reference range of a prespecified assay. At 6 months 67% (ten out of 15) were dialysis independent. This is significantly higher compared with 18% (nine out of 50) in a historical control cohort (P<0.001, Fisher's exact test). Eight serious adverse events (including one death) were reported, none assessed as probably or possibly related to the study drug. CONCLUSIONS: In this pilot study, the use of imlifidase was associated with a better outcome compared with earlier publications, without major safety issues, but the findings need to be confirmed in a randomized controlled trial.Clinical Trial registration number: EUDRACT 2016-004082-39 https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001377-28/results.

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.

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.

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 Sweden's 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.

Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients.

Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, -0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (-72%, -39%, -43%, respectively), serum tryptophan levels increased, resulting in negative RR (-8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.

Context Factors Facilitating and Hindering Patient Participation in Dialysis Care: A Focus Group Study With Patients and Staff.

BACKGROUND: Safe health care of good quality depends on structured and unceasing efforts to progress, promoting strategies tailored to the context, including elements such as patients' preferences. Although patient participation is a common concept in health care, there is yet limited understanding of the factors that facilitate and hinder it in a healthcare context. AIMS: This paper identifies what patients and health professionals depict in terms of enablers and barriers for patient participation in dialysis care. METHODS: An explorative qualitative design was applied with seven focus group discussions with patients, staff, and managers across different types of hospitals, with the texts analyzed with content analysis. RESULTS: The dialysis context represents three key elements-people, resources, and interactions-that can both enable and hinder patient participation. Both barriers and facilitators for patient participation were found to reside at individual, team, and organizational levels, with a greater number of enabling factors implied by both patients and staff. LINKING EVIDENCE TO ACTION: While the dialysis context comprises opportunities for progress in favor of patient participation, a shared understanding of the concept is needed, along with how contextual factors can facilitate conditions for participation by patient preferences. In addition, the most favorable strategy for implementing person-centered care is not yet known, but to facilitate patient participation from a patient perspective, creating opportunities to enable staff and patients to share a common understanding is needed, along with tools to facilitate a dialogue on patient participation.

The IgG-degrading enzyme of Streptococcus pyogenes causes rapid clearance of anti-glomerular basement membrane antibodies in patients with refractory anti-glomerular basement membrane disease.

In anti-glomerular basement membrane (anti-GBM) disease, IgG class autoantibodies induce rapidly progressive glomerulonephritis. Regrettably, many patients are diagnosed at a late stage when even intensive conventional treatment fails to restore renal function The endopeptidase IdeS (Immunoglobulin G degrading enzyme of Streptococcus pyogenes) (imliflidase) rapidly cleaves all human IgG subclasses into F(ab')2 and Fc fragments. We received permission to treat three patients with refractory anti-GBM nephritis without pulmonary involvement on a compassionate basis. All patients were dialysis-dependent for days or weeks when treated, and all had high levels of circulating anti-GBM despite plasma exchange. A single dose of IdeS led to complete clearance of circulating anti-GBM antibodies in all three patients. After about a week, all rebounded but the rebounds were easily managed by plasma exchange in two of three cases. Renal histology demonstrated severe crescentic glomerulonephritis with acute but mainly chronic changes. Staining for the Fc fragment was negative in all while Fab was positive in two patients. Unfortunately, none of the patients regained independent renal function. Thus, treatment with IdeS led to rapid clearance of circulating and kidney bound anti-GBM antibodies. The clinical utility, dosing and usage to preserve renal function remain to be determined.

Long-term follow-up of biomarkers of vascular calcification after switch from traditional hemodialysis to online hemodiafiltration.

Rapid progression of vascular calcification (VC) in hemodialysis (HD) patients is caused by several factors including inflammation and an imbalance between active inducers and inhibitors of VC. Growing evidence shows that online hemodiafiltration (ol-HDF), a combination of diffusive and convective solute transport, has positive effects on the uremic environment that affects patients on dialysis. However, we recently reported that serum 25-hydroxyvitamin D (25(OH)D) decreased after a switch from HD to ol-HDF. As a consequence of this finding, the present study was undertaken to investigate if inducers and inhibitors of VC (i.e. the inactive matrix Gla protein fractions dp-ucMGP and t-ucMGP, fetuin-A, Gla-rich protein (GRP), osteopontin (OPN), bone-specific alkaline phosphatase (BALP), and osteoprotegerin (OPG)) also are affected by ol-HDF. This non-comparative prospective study comprised 35 prevalent patients who were investigated 6, 12, and 24 months after their switch from HD to ol-HDF. Most patients had increased levels of the calcification inhibitors OPN and OPG; and of the inactive calcification inhibitor dp-ucMGP during the study period irrespective of the dialysis modality. BALP and t-ucMGP were mostly within the reference interval, but fetuin-A was mostly below the reference interval during the study period. OPN was significantly associated with BALP and parathyroid hormone, r = 0.62 and r = 0.65 (p < .001), respectively. In conclusion, in contrast to decreased 25(OH)D levels, no differences were found for any of the measured biomarkers of VC following the switch from HD to ol-HDF. Further studies are needed to elucidate how these biomarkers can contribute to calcification risk assessment.

Patient participation in dialysis care-A qualitative study of patients' and health professionals' perspectives.

BACKGROUND AND OBJECTIVE: End-stage renal disease (ESRD) affects a multitude of aspects in the patient's daily life, often entailing their own involvement in various aspects of the treatment. Although patient participation is a core health-care value, what the concept signifies is not yet fully known. The purpose of this paper is to conceptualize patient participation in dialysis care, depicting patients' and health-care professionals' perspectives. DESIGN: This explorative study employed qualitative interviews and content analysis. SETTING AND PARTICIPANTS: Seven focus group discussions engaging 42 key informants were performed, including patients, staff and managers with experience of dialysis care. RESULTS: In dialysis care, patient participation connotes a sharing of information and knowledge, the learning of and planning of care, including partaking in shared decisions with regards to treatment and management, and being involved in the management of one's own health-care treatment and/or self-care activities. Although these attributes were illustrated by all stakeholders, their significance varied: patients suggested that their preferences regarding primary aspects of participation vary, while staff considered patients' performance of dialysis to be the ultimate form of participation. Further, while patients considered multiple ways to execute participation, staff suggested that aspects such as sharing information were a route to, rather than actual, involvement. CONCLUSIONS: Without a common understanding to denote the idea of patient participation, staff and patients are exposed to a potential deficit in terms of facilitating patient participation in everyday encounters of dialysis treatment. Further studies and means to serve a mutual understanding are needed.

Sleep Quality, Fatigue, and Health-Related Quality of Life in Patients on Initial Peritoneal Dialysis and Multiple Modalities after Two Years: A Prospective Study.

The purpose of this study was to investigate changes in sleep quality, fatigue, mental health, and health-related quality of life (HRQoL) over a two-year period among patients undergoing peritoneal dialysis treatment at home. We further explored the extent to which sleep quality, fatigue, and mental health predicted health-related quality of life outcomes. This prospective study included 55 patients. Sleep parameters changed over two years, independently of treatment. Sleep variables at baseline, to some extent, predicted sleep quality after two years. Daytime sleepiness can be a long-term problem. Findings indicate improvements in nocturnal sleep over a two-year time period, independently of dialysis treatment. In contrast, fatigue remained unchanged over the same time period. Transplantation seems to generally benefit the outcome of HRQoL. Strategies to improve sleep and HRQoL may include systematic risk factor modification and efforts to optimise symptomatic treatment.

Computer-Aided Evaluation of Blood Vessel Geometry From Acoustic Images.

A method for computer-aided assessment of blood vessel geometries based on shape-fitting algorithms from metric vision was evaluated. Acoustic images of cross sections of the radial artery and cephalic vein were acquired, and medical practitioners used a computer application to measure the wall thickness and nominal diameter of these blood vessels with a caliper method and the shape-fitting method. The methods performed equally well for wall thickness measurements. The shape-fitting method was preferable for measuring the diameter, since it reduced systematic errors by up to 63% in the case of the cephalic vein because of its eccentricity.

Life in standby: hemodialysis patients' experiences of waiting for kidney transplantation.

AIM AND OBJECTIVES: Our aim was to explore the experiences of hemodialysis patients who are waiting for a kidney transplant. BACKGROUND: Currently, more than 100,000 persons are waiting for kidney transplantation in the United States. In Sweden, the number is exceeding 600. The waiting period for a deceased donor can be one to three years or even longer in Sweden. This can be challenging, since the patients' situation, with chronic treatment and illness, is burdensome and requires advanced self-care. DESIGN: This study included a purposeful sample of eight patients (33-53 years old) who had been undergoing hemodialysis treatment for at least six months and were waiting for kidney transplantation. METHODS: The patients were interviewed, and descriptive content analysis was performed. RESULTS: Four categories emerged: (1) 'The waiting process,' what thoughts and expectations occur and what to do and how to be prepared for the transplant. (2) 'Awareness that time is running out,' patients felt tied up by treatment and by needing to be available for transplantation, and they had concerns about health. (3) 'Need for communication,' patients described needing support from others and continuous information from the staff. (4) 'Having relief and hope for the future,' patients described how to preserve the hope of being able to participate fully in life once again. CONCLUSIONS: This study reveals the need for extra attention paid to patients waiting for kidney transplantation. Patients' experiences during the waiting period indicate that pretransplant patients have an increased need to be prepared for the transition and for life post-transplantation. RELEVANCE TO CLINICAL PRACTICE: Dialysis patients on waiting lists must be prepared for the upcoming life change. This includes preserving hope during the waiting period and being mentally prepared for transplantation and a dialysis-free life. A pretransplant education program to prevent medical and psychosocial issues is highly recommended.

In the backwater of convective dialysis: decreased 25-hydroxyvitamin D levels following the switch to online hemodiafiltration.

BACKGROUND/AIMS: Vitamin D deficiency and elevated serum fibroblast growth factor-23 (FGF23) levels are hallmark features and surrogate markers of adverse clinical outcomes in patients with chronic kidney disease (CKD). Convection of molecules over the dialysis membrane during online hemodiafiltration (ol-HDF) increases the removal of larger waste molecules compared with traditional high-flux hemodialysis (HD). The primary aim of this study was to explore the long-term impact of ol-HDF on serum 25(OH)D and FGF23. METHOD: An observational, prospective, noncomparator study including 35 patients who were switched from HD to ol-HDF. Serum 25(OH)D and FGF23 were measured at baseline (i.e., time of switch to ol-HDF) and at 6, 12, and 24 months. RESULTS: At follow-up time points, there was a significant reduction in serum 25(OH)D compared with baseline (p<0.0001) whereas FGF23 was unaltered (p>0.05). The decrease in 25(OH)D was more prominent in individuals with higher baseline 25(OH)D levels. CONCLUSION: Ol-HDF may lower systemic 25(OH)D levels by convective mechanisms although the clinical significance remains unknown. Further controlled studies are warranted to replicate these findings in larger patient cohorts.

Optical Estimation of Beta 2 Microglobulin during Hemodiafiltration ­ Does It Work?

BACKGROUND: Currently, urea reduction seems to be the most widely used dialysis dose parameter. The aim of this study was to investigate the possibility to monitor beta 2-microglobulin (ß2-M) elimination by utilizing the ultraviolet (UV) absorbance of spent dialysate. METHODS: Blood and spent dialysate were collected during two week's sessions in 8 patients, one week in hemodialysis (HD) and one in hemodiafiltration (HDF). Correlation analysis between UV-wavelengths and concentrations of solutes in spent dialysate was performed. The reduction ratio (RR) of concentrations in blood, dialysate and UV-absorbance were compared. RESULTS: Differences between HD and HDF were discovered in wavelength correlation maxima for the solutes. Relative error in RR (%) was larger (p < 0.05) for ß2-M than for the other solutes. The most reasonable explanation is that ß2-M does not absorb UV-radiation; instead, the absorbance of surrogate substances is measured. CONCLUSION: A high correlation between UV-absorbance and ß2-M can be achieved for HDF but not for HD. Still, UV-absorbance could perhaps be used in solely HDF mode for estimation of ß2-M removal.

Determinants of fibroblast growth factor-23 and parathyroid hormone variability in dialysis patients.

BACKGROUND/AIMS: Treatment strategies for abnormal mineral metabolism in chronic kidney disease are largely based on achieving target ranges of biomarkers that vary considerably over time, yet determinants of their variability are poorly defined. METHODS: Observational study including 162 patients of three dialysis cohorts (peritoneal dialysis, n = 78; hemodialysis, n = 49; hemodiafiltration, n = 35). Clinical and biochemical determinants of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) variability were analyzed in the peritoneal dialysis cohort. All cohorts were used for comparison of PTH and FGF23 intra-subject variability (intra-class correlation), and their intra-subject variability in different modes of dialysis was explored. RESULTS: High PTH variability was independently associated with lower 25-hydroxyvitamin D concentration and factors of lipid and glucose metabolism, whereas high FGF23 variability was mainly associated with lower baseline serum phosphorous. These results were consistent in multivariate and sensitivity analyses. The intra-subject variability of FGF23 was lower than for PTH irrespective of dialysis mode. CONCLUSIONS: Baseline vitamin D status and serum phosphorous are independent determinants of the longitudinal variation in PTH and FGF23, respectively. The clinical utility of FGF23 measurement remains unknown, yet it appears favorable based on its greater temporal stability than PTH in dialysis patients.

Optical measurement of creatinine in spent dialysate.

AIM: The aim of the study was to develop an optical method for the estimation of creatinine (Cr) removal during dialysis using UV-absorbance. MATERIAL AND METHODS: 29 hemodialysis patients on chronic 3-times-a-week hemodialysis were studied in 6 separate studies. Double-beam pectrophotometer was used for the determination of UV-absorbance in the collected spent dialysate samples. A single wavelength (SW) and a multi-wavelength (MW) model were developed using stepwise regression utilizing Cr values from the laboratory as the dependent parameter. The reduction ratio (RR) and total removed Cr (TRCr) were estimated. RESULTS: For blood-Cr RRb (mean ± SD) was 60.9 ± 5.0% (calibration set) and 58.1 ± 6.0% (validation set), for SW UVabsorbance RR_SW was 61.5 ± 5.9% and 57.3 ± 6.0%, and for MW UV-absorbance RR_MW was 65.8 ± 5.8% and 61.7 ± 6.4% respectively. RR_SW and RRb were not statistically different. RR_MW was higher compared to RRb (p < 0.05). TRCr_lab was 13.8 ± 3.8 mmol, TRCr_SW 14.5 ± 2.5 mmol and TRCr_MW 13.8 ± 2.6 mmol, being not statistically different. CONCLUSION: In summary, creatinine removal during dialysis can be estimated as reduction ratio and total removed creatinine with the UV-absorbance technique.

Exon resequencing of the gene encoding UCma/GRP reveals a common carboxy-terminal 138Thr > Ser polymorphism.

BACKGROUND: The upper zone of growth plate and cartilage matrix-associated protein (UCMA), also called G1a-rich protein (GRP), is a novel protein found at sites affected by pathological calcifications. METHODS: We performed a full exon resequencing on DNA samples from 17 chronic kidney disease (CKD) patients (stage 5) and compared the results with 121 healthy controls in a Swedish population. RESULTS: A novel non-synonymous single nucleotide polymorphism (SNP) causing a carboxy-terminal amino acid exchange was found. This SNP involves an alteration of the last ACC codon for threonine in exon 5 (adjacent to the stop codon) to an AGC serine codon (138Thr > Ser). Six controls and two CKD patients were heterozygous for the 138Thr > Ser polymorphism. Both patients had histories of vascular calcification; however, it is uncertain whether this SNP has any significance for the functional domains of the UCMA protein. In addition, a heterozygous transversion mutation was found in a patient at SNP rs4750328 (A/G) in intron 2, involving an exchange of the ancestral A allele to a T base. CONCLUSIONS: The 138Thr > Ser polymorphism seems to be the only non-synonymous SNP found in the UCMA gene in a Swedish population.