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.

Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN. METHODS: Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis-mass spectrometry at baseline (IgAN237-1, n = 103) and at follow-up (IgAN237-2, n = 89). Patients were categorized as "non-progressors" (IgAN237 ≤0.38) and "progressors" (IgAN237 >0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio slopes were calculated. RESULTS: Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71-531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P < .001). Twenty-eight percent and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with chronic eGFR slopes (rho = -0.278, P = .02 for score-1; rho = -0.409, P = .002 for score-2) and with ±180 days eGFR slopes (rho = -0.31, P = .009 and rho = -0.439, P = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median -5.98 versus -1.22 mL/min/1.73 m2 per year for IgAN237-1, P < .001; -3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (P = .001). CONCLUSION: The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner.

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.

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.

Treatment of iron deficiency in patients with chronic kidney disease: A prospective observational study of iron isomaltoside (NIMO Scandinavia)
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AIMS: Iron deficiency is common in patients with chronic kidney disease (CKD). Appropriate iron substitution is critical and intravenous iron is an established therapy for these patients. The objective of this study was to assess treatment routine, -effectiveness, and safety of iron isomaltoside (Monofer®, Pharma-cosmos A/S, Holbaek, Denmark) in CKD patients in clinical practice. MATERIALS AND METHODS: This was a prospective observational study conducted in predialysis CKD patients treated with iron isomaltoside according to the product label and to routine clinical care. RESULTS: The study included 108 patients with predialysis CKD: 22 were in stage 2 - 3, 41 in stage 4, and 45 in stage 5. The mean (standard deviation) age was 67 (15) years, and 55% of patients were male. The majority of patients (65%) received one iron isomaltoside treatment. In patients with a baseline Hb < 10 g/dL, the mean dose of iron isomaltoside in the study was lower than the estimated total iron requirement (567 mg versus 921 mg). A treatment response of Hb ≥ 1 g/dL was achieved in 16/28 (57%) of patients, and the mean post-treatment Hb level was 10.5 g/dL. The probability of retreatment did not correlate with dose, but no dose administered was > 1,000 mg. There were no serious adverse drug reactions. One non-serious adverse drug reaction - injection site discoloration - was reported, and the patient had an uneventful recovery. CONCLUSION: Iron isomaltoside shows a good effectiveness and safety profile in predialysis CKD patients. However, some patients did not receive adequate iron doses to allow for optimal correction of their iron deficiency anemia.

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.

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.

Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial.

BACKGROUND: IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression. METHODS: In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein ≥1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments. RESULTS: Thirty-one patients were randomized (cemdisiran, N =22; placebo, N =9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of -37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of -45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was -98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%). CONCLUSIONS: These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.

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.

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.

A fixed protocol for outpatient clinic routines in the care of patients with severe renal failure.

BACKGROUND: The primary aim of this study was to assess whether a fixed protocol, using a specially trained team, for intermediate follow-up to fulfillment of guideline targets is non-inferior to conventional follow-up in the care of uraemic patients. A secondary aim was to investigate possible impact on patient outcome. METHODS: The cohort comprised 424 patients from seven centers. Inclusion criteria were either serum creatinine exceeding 200 µmol/l or calculated clearance below 30 ml/min, representing CKD 4 or 5a. Six centers followed a standardized protocol (group 1). One center provided controls (group 2). The study design was prospective and interventional. The variables measured were blood hemoglobin, bicarbonate, calcium, phosphate, intact parathyroid hormone, albumin, renal function variables, blood pressure and RAAS blockade. The number of patients achieving the set goals was analyzed as a time trend to determine if the intervention resulted in an improvement. RESULTS: At baseline, group 1 had significantly lower GFR and higher serum creatinine, calcium, phosphate, calcium × phosphate product and bicarbonate, lower mean arterial pressure (MAP), systolic blood pressures and less use of RAAS. During the intervention, group 1 improved in the direction of guidelines for blood hemoglobin, albumin, bicarbonate and MAP. Outcome of secondary endpoints gave a risk of death of 30% in both groups, while the risk of renal replacement therapy was higher in group 1. CONCLUSIONS: However, the time to renal replacement therapy was significantly shorter in the intervention group, indicating that other variables than guideline achievements are important for the patient.

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.

Time-averaged concentration estimation of uraemic toxins with different removal kinetics: a novel approach based on intradialytic spent dialysate measurements.

Background: Kt/Vurea is the most used marker to estimate dialysis adequacy; however, it does not reflect the removal of many other uraemic toxins, and a new approach is needed. We have assessed the feasibility of estimating intradialytic serum time-averaged concentration (TAC) of various uraemic toxins from their spent dialysate concentrations that can be estimated non-invasively online with optical methods. Methods: Serum and spent dialysate levels and total removed solute (TRS) of urea, uric acid (UA), indoxyl sulphate (IS) and ß2-microglobulin (ß2M) were evaluated with laboratory methods during 312 haemodialysis sessions in 78 patients with four different dialysis treatment settings. TAC was calculated from serum concentrations and evaluated from TRS and logarithmic mean concentrations of spent dialysate (MlnD). Results: Mean (± standard deviation) intradialytic serum TAC values of urea, UA, ß2M and IS were 10.4 ± 3.8 mmol/L, 191.6 ± 48.1 µmol/L, 13.3 ± 4.3 mg/L and 82.9 ± 43.3 µmol/L, respectively. These serum TAC values were similar and highly correlated with those estimated from TRS [10.5 ± 3.6 mmol/L (R 2 = 0.92), 191.5 ± 42.8 µmol/L (R 2 = 0.79), 13.0 ± 3.2 mg/L (R 2 = 0.59) and 82.7 ± 40.0 µmol/L (R 2 = 0.85)] and from MlnD [10.7 ± 3.7 mmol/L (R 2 = 0.92), 191.6 ± 43.8 µmol/L (R 2 = 0.80), 12.9 ± 3.2 mg/L (R 2 = 0.63) and 82.2 ± 38.6 µmol/L (R 2 = 0.84)], respectively. Conclusions: Intradialytic serum TAC of different uraemic toxins can be estimated non-invasively from their concentration in spent dialysate. This sets the stage for TAC estimation from online optical monitoring of spent dialysate concentrations of diverse solutes and for further optimization of estimation models for each uraemic toxin.

Utilization of UV absorbance for estimation of phosphate elimination during hemodiafiltration.

BACKGROUND: Phosphate is an important factor in explaining the high progress of vascular calcification among dialysis patients. Today, phosphate concentration is measured in plasma on a regular basis. The aim of this study was to find out if it is possible to estimate total removed phosphate (TRp) in spent dialysate utilizing UV absorbance during hemodiafiltration. METHODS: Eleven patients were monitored online with UV absorbance at 297 nm, three times during one week each (n = 33). Dialysate samples were taken at different times during treatment and from a collection tank to chemically determine phosphate concentrations. Two mathematical models (UVIND and UVGROUP) were tested to estimate TRp with supervision by UV absorbance and compared with TRp measured in the tank (reference). RESULTS: High correlation between UV absorbance and phosphate concentration for each single patient and lower for the whole group together was found. TRp was (mean ± SD) 30.7 ± 7.3 mmol for the reference and 30.8 ± 8.2 and 29.1 ± 5.2 mmol for UVIND and UVGROUP, respectively (p > 0.05). CONCLUSION: This study demonstrates a novel possibility to estimate TRp based on linear relationship between online monitoring of UV absorbance and concentration of phosphate in spent dialysate.

Evaluation of an individual sleep intervention programme in people undergoing peritoneal dialysis treatment.

AIMS AND OBJECTIVES: This study aimed to evaluate effects of a non-pharmacological intervention on sleep, activity and fatigue in patients receiving peritoneal dialysis by the use of both actigraphy registration and self-assessed questionnaires. BACKGROUND: Insomnia is estimated to affect up to 60% of haemo- and peritoneal dialysis patients. It is associated with two common uremic symptoms, pruritus and restless legs syndrome. To our knowledge, no interventions have been evaluated by actigraphy. DESIGN: A prospective multiple baseline single-case experimental design. METHODS: Two women and seven men with sleep problems, 48-77 years, treated with PD participated in a 17-week study from January 2009 to February 2011. Two interventions were separately implemented. First, a pressure-relieving mattress and second, a four week individual sleep hygiene and sleep scheduling intervention. The two interventions were evaluated both objectively by actigraphy and subjectively by questionnaires. RESULTS: A total of 315 sleep-wake cycles from nine individuals were evaluated. Three patients improved clinically significantly in five or more of the nine outcomes, i.e. sleep onset latency, nocturnal sleep duration, numbers and duration of napping, movement and fragmentation index, number of steps, metabolic equivalent unit, sleep efficiency and fatigue. The other six patients also showed improvements but to a lesser degree. Physical activity advice was the intervention that yielded most sleep improvements. CONCLUSIONS: This study illuminates the need for regular assessment of sleep and tiredness. It also demonstrates how a non-pharmacological treatment and self-management can be applied with renal supportive care to improve sleep quality. RELEVANCE TO CLINICAL PRACTICE: This study is a clinical example of a non-pharmacological intervention with supportive care and self-management. This model can improve health and reduce the pharmacological burden because hypnotics can be replaced by sleep hygiene self-care activities.

New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria.

BACKGROUND: Systemic corticosteroid treatment has been shown to exert some protection against renal deterioration in IgA nephropathy (IgAN) but is not commonly recommended for long-term use due to the well-known systemic side effects. In this study, we investigated the efficacy and safety of a new enteric formulation of the locally acting glucocorticoid budesonide (Nefecon®), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria. METHODS: Budesonide 8 mg/day was given to 16 patients with IgAN for 6 months, followed by a 3-month follow-up period. The efficacy was measured as change in 24-h urine albumin excretion, serum creatinine and estimated glomerular filtration rate (eGFR). RESULTS: The median relative reduction in urinary albumin excretion was 23% during the treatment period (interquartile range: -0.36 to -0.04, P = 0.04) with pretreatment values ranging from 0.3 to 6 g/24 h (median: 1.5 g/24 h). The median reduction in urine albumin peaked at 40% (interquartile range: -0.58 to -0.15) 2 months after treatment discontinuation. Serum creatinine was reduced by 6% (interquartile range: -0.12 to -0.02; P = 0.003), and eGFR [Modification of Diet in Renal Disease (MDRD)] increased ∼8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed. CONCLUSIONS: In the present pilot study, enteric budesonide targeted to the ileocecal region had a significant effect on urine albumin excretion, accompanied by a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation, while eGFR calculated from Cockcroft-Gault equation and cystatin C was not changed. Enteric budesonide may represent a new treatment of IgAN warranting further investigation.

Fragmented sleep: an unrevealed problem in peritoneal dialysis patients.

OBJECTIVE: The aim of this study was to describe the sleep-wake cycle, sleep quality, fatigue and Health Related Quality of Life (HRQoL) measured with questionnaires, actigraphy and a sleep diary during a one-week period in patients undergoing peritoneal dialysis (PD) treatment at home. A further aim was to explore differences compared with patients with coronary artery disease (CAD) and individuals from the general population. MATERIAL AND METHODS: In this study one-week actigraphy registration, four questionnaires (Uppsala Sleep Inventory, SF-36, FACIT-fatigue, International Restless Legs Study Groups' form) and a sleep diary were used. RESULTS: Data from 68 participants and 470 nights were collected. PD patients (n = 28) had more fragmented sleep (p < 0.001) and worse sleep efficiency (SE%) (p < 0.0001) than the CAD (n = 22) and the population (n = 18) groups. Pruritus (57%), restless legs (46%) and fatigue (89%) were prevalent in PD patients. Pruritus correlated with fragmented sleep (r = -0.45, p = 0.01) and SE (r = -0.49, p = 0.01). In HRQoL, the physical component score was decreased in the PD and CAD groups (p < 0.01) compared to the population group. CONCLUSIONS: To the authors' knowledge this study is the first to demonstrate that PD patients have deteriorated sleep, with serious fragmentation measured by a one-week actigraphy registration. Further, PD patients exhibit worse sleep quality than CAD patients and individuals in the population. Evaluation of sleep in clinical practice is highly recommended since PD patients are vulnerable individuals with extended self-care responsibilities and at risk for comorbidity secondary to insufficient sleep. Future research on whether PD patients' sleep problems and fatigue can be improved by an individual non-pharmacological intervention programme is required.