Genetic Risk Factors in Lupus Nephritis and IgA Nephropathy - No Support of an Overlap

Background: IgA nephropathy (IgAN) and nephritis in Systemic Lupus Erythematosus (SLE) are two common forms of glomerulonephritis in which genetic findings are of importance for disease development. We have recently reported an association of IgAN with variants of TGFB1. In several autoimmune diseases, particularly in SLE, IRF5, STAT4 genes and TRAF1-C5 locus have been shown to be important candidate genes. The aim of this study was to compare genetic variants from the TGFB1, IRF5, STAT4 genes and TRAF1-C5 locus with susceptibility to IgAN and lupus nephritis in two Swedish cohorts. Patients and Methods: We genotyped 13 single nucleotide polymorphisms (SNPs) in four genetic loci in 1252 DNA samples from patients with biopsy proven IgAN or with SLE (with and without nephritis) and healthy age-and sex-matched controls from the same population in Sweden. Results: Genotype and allelic frequencies for SNPs from selected genes did not differ significantly between lupus nephritis patients and SLE patients without nephritis. In addition, haplotype analysis for seven selected SNPs did not reveal a difference for the SLE patient groups with and without nephritis. Moreover, none of these SPNs showed a significant difference between IgAN patients and healthy controls. IRF5 and STAT4 variants remained significantly different between SLE cases and healthy controls. In addition, the data did not show an association of TRAF1-C5 polymorphism with susceptibility to SLE in this Swedish population. Conclusion: Our data do not support an overlap in genetic susceptibility between patients with IgAN or SLE and reveal no specific importance of SLE associated SNPs for the presence of lupus nephritis.Original Publication: Mai Tuyet Vuong, Iva Gunnarsson, Sigrid Lundberg, Elisabet Svenungsson, Lars Wramner, Anders Fernström, Ann-Christine Syvanen, Lieu Thi Do, Stefan H. Jacobson and Leonid Padyukov, Genetic Risk Factors in Lupus Nephritis and IgA Nephropathy - No Support of an Overlap, 2010, PLOS ONE, (5), 5. http://dx.doi.org/10.1371/journal.pone.0010559 Licensee: Public Library of Science (PLoS) http://www.plos.org/</p

Genetic variation in the transforming growth factor-β1 gene is associated with susceptibility to IgA nephropathy

Background. There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis

Factors affecting body weight development and eating behaviour in patients on continuous ambulatory peritoneal dialysis treatment

Continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) have different meta bolic effects in dialysis patients, since absorption of intraperitoneal glucose implies an additional energy source in CAPD patients. In spite of this, protein-energy malnutrition is known to occur frequently, both in patients on hemodialysis and in patients on CAPD, and an association with increased morbidity and mortality is well established. It is therefore of great importance to identify factors which have the potential of negatively influencing the nutritional state. In this thesis, it is demonstrated that taste acuity of primary tastes in end-stage renal disease (ESRD) patients is hampered in the form of increased recognition thresholds. The taste thresholds were significantly higher for salt and bitter in preuremic patients, compared to control subjects. In CAPDpatients, taste recognition of bitter was impaired and in HD patients, recognition of salty taste was impaired. Patients with ESRD have significantly fewer fungiform taste buds, which might be an important factor contributing to the impaired taste acuity. In addition to the study of the number of taste buds, the presence of peripheral nervous tissue in taste buds with the aid of specific markers (primary antibodies) was also analysed. With these antibodies, no major immunohistochemical differences were disclosed between uremic patients and healthy controls. In a study of energy intake in CAPD patients (five days food recording), it is also established that dietary energy intake from carbohydrates, protein and fat is lower in patients treated with CAPD than in those treated with hemodialysis, although the energy percentage composition of the dietary macronutrients is unaffected. Transperitoneal energy intake compensates for this lower dietary energy intake, and makes total energy intake almost the same in CAPD and HD patients, but with a change in the composition of the diet of CAPD patients towards a significantly higher carbohy drate percentage in energy intake. The level of total energy intake observed places both patient groups in the risk zone for developing malnutrition. CAPD patients have a slower gastric emptying rate, as measured with scintigraphy. This impair ment of gastric emptying rate correlates with disturbances in the normal myoelectric rhythm of the stomach (tachygastria), as measured with electrogastrography. A body composition analysis of CAPD patients, as studied with computed tomography of the abdomen and of the right thigh, as well as with dual energy x-ray absorptiometry, reveals an increase in the intraabdominal fat area after commencement of peritoneal dialysis. Thus CAPD induces a dis tribution of body fat that resembles the pattern observed in the metabolic syndrome. In conlusion, several factors which have the potential of negatively influencing the nutritional state in CAPD patients have been identified. Moreover, a metabolic consequence in the form of an increase in intraabdominal fat is demonstrated in patients treated with CAPD, which may acceler ate the development of risk factors for cardiovascular disease. Stockholm 199

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

The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease

Circulating alkaline phosphatase (ALP) is an independent cardiovascular risk marker. Serum bone ALP (BALP) isoforms indicate bone turnover and comprise approximately 50% of total circulating ALP. In chronic kidney disease (CKD), mortality is highest in patients with increased ALP and BALP and low bone turnover. However, not all low bone turnover states are associated with increased mortality. Chronic inflammation and oxidative stress, features of protein energy wasting syndrome, induce cardiovascular BALP activity and fibro-calcification, while bone turnover is suppressed. Circulating BALP isoform B1x is associated with low ALP and low bone turnover and has been exclusively detected in CKD. We investigated the association of serum B1x with survival, abdominal aortic calcification (AAC) score, and aortic pulse wave velocity (PWV) in CKD. Serum ALP, BALP isoforms, parathyroid hormone (PTH), PWV, and AAC were measured repeatedly over 2 years in 68 prevalent dialysis patients. Mortality was assessed after 5 years. B1x was detected in 53 patients. A competing risk analysis revealed an association of B1x with improved 5-year survival; whereas, baseline PWV, but not AAC score, predicted mortality. However, PWV improved in 26 patients (53%), and B1x was associated with variation of PWV over time (p = 0.03). Patients with B1x had lower PTH and total ALP, suggesting an association with lower bone turnover. In conclusion, B1x is associated with time-varying PWV, lower circulating ALP, and improved survival in CKD, and thus may be an indicator of a reduced cardiovascular risk profile among patients with low bone turnover

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

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

Objective: This study aimed at evaluate effects of a individually designed nonpharmacological intervention on sleep, activity and fatigue in peritoneal dialysis (PD) by use of both actigraphy registration and self-assessed questionnaires. 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. 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: Totally 315 sleep-wake cycles from nine individuals were evaluated. Of the nine measured outcome variables i.e. sleep onset latency, nocturnal sleep duration, numbers and duration of napping, movement and fragmentation index (MFI), number of steps, metabolic equivalent unit (METs), sleep efficiency and fatigue, three patients improved clinically significantly in five or more of the outcomes. 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 shows that patients on peritoneal dialysis treatment have a wide variety of sleep problems and that an individual sleep hygiene and sleep scheduling program can be applied with clinically significant improvements even in this heterogeneous and frail patient group. The intervention should be easy to use in daily clinical routines