| 1. |
- Jonsson, Per, et al.
(author)
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Venous chambers in clinical use for hemodialysis have limited capacity to eliminate microbubbles from entering the return bloodline : an in vitro study
- 2023
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In: Artificial Organs. - : John Wiley & Sons. - 0160-564X .- 1525-1594. ; 47:6, s. 961-970
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Journal article (peer-reviewed)abstract
- Background: During hemodialysis (HD), blood passes through an extracorporeal circuit (ECC). To prevent air administration to the patient, a venous chamber (chamber) is located before the blood return. Microbubbles (MBs) may pass through the chamber and end up as microemboli in organs such as the brain and heart. This in vitro study investigated the efficacy of various chambers in MB removal.Materials and Methods: The in vitro recirculated setting of an ECC included an FX10 dialyzer, a dextran-albumin solution to mimic blood viscosity and chambers with different flow characteristics in clinical use (Baxter: AK98 and Artis, Fresenius: 5008 and 6008) and preclinical test (Embody: Emboless®). A Gampt BCC200 device measured the presence and size of MBs (20–500 μm). Percentage change of MBs was calculated: ΔMB% = 100*(outlet–inlet)/inlet for each size of MB. Blood pump speed (Qb) was 200 (Qb200) or 300 (Qb300) ml/minute. Wilcoxon paired test determined differences.Results: With Qb200 median ΔMB% reduction was: Emboless −58%, AK98 −24%, Fresenius 5008 −23%, Artis −8%, and Fresenius 6008 ± 0%. With Qb300 ΔMB% was: Emboless −36%, AK98 ± 0%, Fresenius 5008 ± 0%, Artis +25%, and Fresenius 6008 + 21%. The Emboless was superior to all other chambers with Qb200 and Qb300 (p < 0.001). Further, the Emboless with Qb300 still eliminated more MBs than all other chambers with Qb200 (p ≤ 0.003).Conclusion: The results from the present study indicate that flow characteristics of the chamber and the Qb are important factors to limiting exposure of MB to the return bloodline. The Emboless chamber reduced MBs more effective than those chambers in clinical use investigated.
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| 2. |
- Vollmer, Tino, et al.
(author)
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An in-vitro assay using human spermatozoa to detect toxicity of biologically active substances
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Journal article (peer-reviewed)abstract
- Identifying the key toxic players within an in-vivo toxic syndrome is crucial to develop targeted therapies. Here, we established a novel method that characterizes the effect of single substances by means of an ex-vivo incubation set-up. We found that primary human spermatozoa elicit a distinct motile response on a (uremic) toxic milieu. Specifically, this approach describes the influence of a bulk toxic environment (uremia) as well as single substances (uremic toxins) by real-time analyzing motile cellular behavior. We established the human spermatozoa-based toxicity testing (HSTT) for detecting single substance-induced toxicity to be used as a screening tool to identify in-vivo toxins. Further, we propose an application of the HSTT as a method of clinical use to evaluate toxin-removing interventions (hemodialysis).
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| 3. |
- Blaha, M., et al.
(author)
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Analysis of extracorporeal photopheresis within the frame of the WAA register
- 2021
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In: Transfusion and apheresis science. - : Elsevier. - 1473-0502 .- 1878-1683. ; 60:5
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Journal article (peer-reviewed)abstract
- The aim of the study was to investigate safety and if extracorporeal photopheresis (ECP) may change health criteria (HC) and quality of life (QoL).Material and method: 560 patients (33 % women) were treated with ECP for a total of 13,871 procedures during a 17-years period. Mean age was 48 years (±18, range 3−81 years). Self-estimation of QoL was graded: 0 (suicidal) up to 10 (best ever) and HC: 0 (Bed ridden, ICU condition) up to 10 (athletic). Adverse events were analyzed. ANOVA and paired comparisons were performed.Results: Patients were treated due to graft versus host disease (GVHD, n = 317), skin lymphoma (n = 70), solid organ transplants (n = 47), skin diseases (n = 20) and other diseases (n = 106). Adverse events (AEs) were registered in 5.4 % of the first treatments and in 1.2 % of the subsequent procedures. Severe AEs were present in 0.04 % of all procedures. No patient died due to the procedure. Tingling and stitching were the most common AE. For those with GVHD an improvement was noticed within approximately 10 procedures of ECP in the severity stage, QoL (from a mean of 6.1 to 6.8, p < 0.002) and the HC (6.1 -> 6.4, p < 0.014) and improved further with added procedures.Conclusion: Photopheresis is an established therapy with few side effects. The present study of soft variables indicate that GVHD shows benefits upon ECP within approximately 10 procedures in regard to the severity of mainly skin GVHD, and lower baseline levels of HC and QoL.
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| 4. |
- Carle, Vanessa, et al.
(author)
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Development of Selective FXIa Inhibitors Based on Cyclic Peptides and Their Application for Safe Anticoagulation
- 2021
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:10, s. 6802-6813
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Journal article (peer-reviewed)abstract
- Coagulation factor XI (FXI) has emerged as a promising target for the development of safer anticoagulation drugs that limit the risk of severe and life-threatening bleeding. Herein, we report the first cyclic peptide-based FXI inhibitor that selectively and potently inhibits activated FXI (FXIa) in human and animal blood. The cyclic peptide inhibitor (Ki = 2.8 ± 0.5 nM) achieved anticoagulation effects that are comparable to that of the gold standard heparin applied at a therapeutic dose (0.3-0.7 IU/mL in plasma) but with a substantially broader estimated therapeutic range. We extended the plasma half-life of the peptide via PEGylation and demonstrated effective FXIa inhibition over extended periods in vivo. We validated the anticoagulant effects of the PEGylated inhibitor in an ex vivo hemodialysis model with human blood. Our work shows that FXI can be selectively targeted with peptides and provides a promising candidate for the development of a safe anticoagulation therapy.
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| 5. |
- Dahlqvist, Johanna, 1979-, et al.
(author)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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In: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Journal article (peer-reviewed)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 6. |
- Ekman, Diana, et al.
(author)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
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Journal article (peer-reviewed)abstract
- Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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| 7. |
- Esberg, Anders, et al.
(author)
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Oral Microbiota Profile in Patients with Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis
- 2022
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In: Microorganisms. - : MDPI. - 2076-2607. ; 10:8
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Journal article (peer-reviewed)abstract
- Microbiota has been associated with autoimmune diseases, with nasal Staphylococcus aureus being implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV). Little is known about the role of oral microbiota in AAV. In this study, levels of IgG antibodies to 53 oral bacterial species/subspecies were screened using immunoblotting in plasma/serum in pre-symptomatic AAV-individuals (n = 85), matched controls, and established AAV-patients (n = 78). Saliva microbiota from acute-AAV and controls was sequenced from 16s rDNA amplicons. Information on dental status was extracted from a national register. IgG levels against oral bacteria were lower in established AAV versus pre-AAV and controls. Specifically, pre-AAV samples had, compared to controls, a higher abundance of periodontitis-associated species paralleling more signs of periodontitis in established AAV-patients than controls. Saliva microbiota in acute-AAV showed higher within-sample diversity but fewer detectable amplicon-sequence variants and taxa in their core microbiota than controls. Acute-AAV was not associated with increased abundance of periodontal bacteria but species in, e.g., Arthrospira, Staphylococcus, Lactobacillus, and Scardovia. In conclusion, the IgG profiles against oral bacteria differed between pre-AAV, established AAV, and controls, and microbiota profiles between acute AAV and controls. The IgG shift from a pre-symptomatic stage to established disease cooccurred with treatment of immunosuppression and/or antibiotics.
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| 8. |
- Forsberg, Ulf, et al.
(author)
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Air contamination during medical treatment results in deposits of microemboli in the lungs : an autopsy study
- 2019
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In: International Journal of Artificial Organs. - : Sage Publications. - 0391-3988 .- 1724-6040. ; 42:9, s. 477-481
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Journal article (peer-reviewed)abstract
- Introduction: Microbubbles of air may enter into patients during conventional hemodialysis, infusions of fluids, or by injections. The aim of this study was to investigate whether the air that enters the patient during hemodialysis can be detected in the lungs after death, and if so, whether this may be related to tissue damage. Methods: The material consisted of lung tissue from five chronic hemodialysis patients who died either during (two) or after hemodialysis (range 10 min from start until 3333 min after the last hemodialysis session); as reference group tissue was taken from seven patients who died due to amyotrophic lateral sclerosis. The lung tissue was investigated by microscopy after autopsy using a fluorescein-marked polyclonal antibody against fibrinogen as a marker for clots preformed before death. Results: All five hemodialysis patients had microbubbles of air in the lung tissue, whereas two of seven amyotrophic lateral sclerosis patients had such findings (Fisher's test p = 0.0278, relative risk = 3.5, confidence interval: 1.08-11.3). There were more microbubbles of air/10 randomly investigated microscopic fields of tissue in the hemodialysis patients than the amyotrophic lateral sclerosis patients (Student's test, p < 0.05). All hemodialysis patients had a medium graded extent of pulmonary fibrosis that was not found in any of the ALS patients. The microbubbles of air were surrounded by fibrin as a sign of development of clots around the air bubbles while the patients were still alive. Conclusion: Exposure to microbubbles of air during various treatments such as hemodialysis may result in microemboli. Future studies should clarify whether microbubbles of air contribute to tissue scarring. We suggest preventive measures against the exposure to microbubbles of air during especially repeated exposures such as hemodialysis.
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| 9. |
- Forsberg, Ulf, et al.
(author)
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Microemboli induced by air bubbles may be deposited in organs as a consequence of contamination during medical care
- 2023
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In: Clinical Kidney Journal. - : Oxford University Press. - 2048-8505 .- 2048-8513. ; 16:1, s. 159-166
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Journal article (peer-reviewed)abstract
- Background: Larger volumes of accidental air infused during medical care may end up as emboli while microbubbles of air are supposed to be absorbed and cause no harm. The aim of this autopsy study was to investigate if microbubbles of air accidently entering the bloodline may be detected as microemboli (ME) in tissue such as lungs, brain and heart. If so, do differences in prevalence exist between haemodialysis (HD) and amyotrophic lateral sclerosis (ALS) patients.Methods: Included were data from 44 patients treated by medical healthcare before death. Twenty-five cases had been treated with chronic HD and 19 cases died from ALS. Since air in the bloodline activates coagulation, ME could appear. To discriminate between microbubbles caused by artificial contamination during autopsy versus microbubbles deposited in vivo, tissues were stained with a polyclonal fluorescent antibody against fibrinogen, fibrin and fragments E and D. Fluorescence staining was used to visualize ME counted within 25 microscopic fields (600x) of a tissue preparation. One tissue preparation was used if available from the lung, heart and frontal lobe of the brain and in five cases also the cerebellum.Results: Microbubbles can be verified at autopsy as ME in the lung, heart and brain in tissue from patients exposed to more extensive medical care. There were significantly more ME in the lungs versus the heart or brain. Women had fewer ME than men. The HD group had a higher median of ME per section than the ALS group (lung: 6 versus 3, P = .007; heart: 2.5 versus 1, P = .013; brain: 7.5 versus 2, P = .001) and had more sections with ME findings than the ALS group (P = .002). A correlation existed between the time on HD (months) and ME in the lungs.Conclusions: More ME were present in HD patients compared with those who suffered from ALS. Minimizing air contamination from syringes, infusions and bloodlines will decrease ME and subsequent tissue injury. Lay Summary Larger volumes of accidental air infused during medical care may end up as emboli while microbubbles of air are supposed to be absorbed and cause no harm. Microbubbles can be verified at autopsy as microemboli (ME) by air in lung, heart and brain in tissue from patients exposed to dialysis and more cannulation and infusions. Minimizing air exposure from syringes, infusions and bloodlines may decrease the risk of ME by air and subsequent tissue injury.
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| 10. |
- Fransson, Filip, et al.
(author)
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Kidney function in patients with bipolar disorder with and without lithium treatment compared with the general population in northern Sweden : results from the LiSIE and MONICA cohorts
- 2022
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In: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 9:10, s. 804-814
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Journal article (peer-reviewed)abstract
- Background: The clinical relevance of lithium nephropathy is subject to debate. Kidney function decreases with age and comorbidities, and this decline might lead to attribution bias when erroneously ascribed to lithium. We aimed to investigate whether patients with bipolar or schizoaffective disorder had faster decline in estimated glomerular filtration rate (eGFR) compared with the general population, whether observed differences in the steepness of the decline were attributable to lithium, and whether such changes depended on the length of lithium exposure.Methods: In this cross-sectional cohort study, we used clinical data from the Lithium–Study into Effects and Side-effects (LiSIE) retrospective cohort study, which included patients with bipolar disorder or schizoaffective disorder whose medical records were reviewed up to Dec 31, 2017, and the WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, covering a representative sample of the general population in northern Sweden aged 25–74 years. The primary outcome was the age-associated decline of creatinine-based eGFR, assessed using linear regression. We adjusted for sex and grouped for different lengths of lithium exposure (never or <1 year, 1–5 years, >5–10 years, and >10 years). For patients with moderate-to-severe kidney disease we identified the underlying nephropathy in the case records.Findings: From LiSIE, we included 785 patients (498 [63%] female and 287 [37%] male), with a mean age of 49·8 years (SD 13·2; range 25–74). From MONICA, we included 1549 individuals (800 [52%] female and 749 [48%] male), with a mean age of 51·9 years (13·8; 25–74). No ethnicity data were collected. Adjusted for duration of lithium exposure, eGFR declined by 0·57 mL/min/1·73 m2/year (95% CI 0·50–0·63) in patients with bipolar disorder or schizoaffective disorder and by 0·57 mL/min/1·73 m2/year (0·53–0·61) in the reference population. Lithium added 0·54 mL/min/1·73 m2 (0·43–0·64) per year of treatment (p<0·0001). After more than 10 years on lithium, decline was significantly steeper than in all other groups including the reference population (p<0·0001). Lithium nephropathy was judged to be the commonest cause of moderate-to-severe chronic kidney disease, but comorbidities played a role. The effect of lithium on eGFR showed a high degree of inter-individual variation.Interpretation: Steeper eGFR decline in patients with bipolar disorder or schizoaffective disorder can be attributed to lithium, but the trajectory of kidney function decline varies widely. Comorbidities affecting kidneys should be treated assertively as one possible means to affect the trajectory. In patients with a fast trajectory, a trade-off is required between continuing lithium to treat mental health problems and discontinuing lithium for the sake of renal health.Funding: Norrbotten County Research and Learning Fund Sweden, Visare Norr (Northern County Councils Regional Federation Fund), Swedish Kidney Foundation (Njurfonden), Swedish Kidney Association (Njurförbundet), Norrbotten section.Translation: For the Swedish translation of the Summary see Supplementary Materials section.
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| 11. |
- Goto, Junko, et al.
(author)
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Interdialytic weight gain of less than 2.5% seems to limit cardiac damage during hemodialysis
- 2021
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In: International Journal of Artificial Organs. - : SAGE Open. - 0391-3988 .- 1724-6040. ; 44:8, s. 539-550
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Journal article (peer-reviewed)abstract
- Aims: To investigate if a single low-flux HD induces a rise in cardiac biomarkers and if a change in clinical approach may limit such mechanism.Material and methods: A total of 20 chronic HD patients each underwent three different study-dialyses. Dialyzers (low-flux polysulfone, 1.8 sqm) had been stored either dry or wet (Wet) and the blood level in the venous chamber kept low or high. Laboratory results were measured at baseline, 30 and 180 min, adjusted for the effect of fluid shift. Ultrasound measured microemboli signals (MES) within the return line.Results: Hemodialysis raised cardiac biomarkers (p < 0.001): Pentraxin 3 (PTX) at 30 min (by 22%) and at 180 min PTX (53%), Pro-BNP (15%), and TnT (5%), similarly for all three HD modes. Baseline values of Pro-BNP correlated with TnT (rho = 0.38, p = 0.004) and PTX (rho = 0.52, p < 0.001). The changes from pre- to 180 min of HD (delta-) were related to baseline values (Pro-BNP: rho = 0.91, p < 0.001; TnT: rho = 0.41, p = 0.001; PTX: rho = 0.29, p = 0.027). Delta Pro-BNP (rho = 0.67, p < 0.001) and TnT (rho = 0.38, p = 0.004) correlated with inter-dialytic-weight-gain (IDWG). Biomarkers behaved similarly between the HD modes. The least negative impact was with an IDWG <= 2.5%. Multiple regression analyses of the Wet-High mode does not exclude a relation between increased exposure of MES and factors such as release of Pro-BNP.Conclusion: Hemodialysis, independent of type of dialyzer storage, was associated with raised cardiac biomarkers, more profoundly in patients with higher pre-dialysis values and IDWG. A limitation in IDWG to <2.5% and prolonged ultrafiltration time may limit cardiac strain during HD, especially in patients with cardiovascular risk.
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| 12. |
- Goto, Junko, et al.
(author)
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Myocardial markers are highly altered by higher rates of fluid removal during hemodialysis
- 2024
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In: Hemodialysis International. - : John Wiley & Sons. - 1492-7535 .- 1542-4758. ; 28:1, s. 17-23
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Journal article (peer-reviewed)abstract
- Introduction: Although hemodialysis is lifesaving in patients with kidney failure extensive interdialytic weight gain (IDWG) between dialyses worsens the prognosis. We recently showed a strong correlation between IDWG and predialytic values of cardiac markers. The aim of the present study was to evaluate if the cardiac markers N-terminal pro-B-type natriuretic peptide (proBNP) and troponin T were influenced by IDWG and speed of fluid removal (ultrafiltration-rate).Methods: Twenty hemodialysis patients performed in total 60 hemodialysis (three each). Predialytic values of proBNP and troponin T and changes from predialysis to 180 min hemodialysis (180–0 min) were compared with the IDWG calculated in percent of body weight. The ultrafiltration-rate was adjusted (UF-rateadj) to IDWG: (100 × weight gain between dialysis [kg])/(estimated body dry weight [kg] × length of hemodialysis session [hours]).Results: UF-rateadj correlated (Spearman) with (1) predialytic values of IDWG (r = 0.983, p < 0.001), proBNP (r = 0.443, p < 0.001), and troponin T (r = 0.296, p = 0.025); and (2) differences in proBNP180–0min (r = 0.572, p < 0.001) and troponin T180–0min (r = 0.400, p = 0.002). UF-ratesadj above a breakpoint of 0.60 caused more release of proBNP180–0min (p = 0.027). Remaining variables in multiple regression analysis with ProBNP180–0min as dependent factor were predialytic proBNP (p < 0.001) and the ultrafiltration-rate (p < 0.001).Conclusion: Higher UF-rateadj during dialysis was correlated to increased levels of cardiac markers. Data support a UF-rateadj lower than 0.6 to limit such increase. Further studies may confirm if limited fluid intake and a lower UF-rateadj should be recommended to prevent cardiac injury during dialysis.
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| 13. |
- Groth, Thomas, et al.
(author)
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Wearable and implantable artificial kidney devices for end-stage kidney disease treatment : current status and review
- 2023
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In: Artificial Organs. - : John Wiley & Sons. - 0160-564X .- 1525-1594. ; 47:4, s. 649-666
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Research review (peer-reviewed)abstract
- Background: Chronic kidney disease (CKD) is a major cause of early death worldwide. By 2030, 14.5 million people will have end-stage kidney disease (ESKD, or CKD stage 5), yet only 5.4 million will receive kidney replacement therapy (KRT) due to economic, social, and political factors. Even for those who are offered KRT by various means of dialysis, the life expectancy remains far too low.Observation: Researchers from different fields of artificial organs collaborate to overcome the challenges of creating products such as Wearable and/or Implantable Artificial Kidneys capable of providing long-term effective physiologic kidney functions such as removal of uremic toxins, electrolyte homeostasis, and fluid regulation. A focus should be to develop easily accessible, safe, and inexpensive KRT options that enable a good quality of life and will also be available for patients in less-developed regions of the world.Conclusions: Hence, it is required to discuss some of the limits and burdens of transplantation and different techniques of dialysis, including those performed at home. Furthermore, hurdles must be considered and overcome to develop wearable and implantable artificial kidney devices that can help to improve the quality of life and life expectancy of patients with CKD.
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| 14. |
- Hadimeri, Ursula
(author)
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Factors affecting the physical characteristics of arterio-venous fistula in patients with renal failure
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Background and PurposeA patent access is vital for a dialysis patient. The arterio-venous fistula (AVF), the most important access for haemodialysis (HD), is frequently affected by extensive complications such as stenosis and occlusions.Study I: To investigate whether the dimensions of AVFs used for performing haemodialysis were affected by the original disease.Study II: To investigate if the diameter of the distal radiocephalic fistula could influence left ventricular variables in stable haemodialysis patients.Study III: To investigate whether a single Far Infrared (FIR) light treatment could alter blood velocity, AVF diameter or inflammatory markers.Study IV: To evaluate in what extent the renal diagnosis and radiological interventions affected the dysfunction of AVF and results of percutaneous transluminal angioplasty (PTA).Materials and methodsStudy I: The lumen diameter of the AVF was studied by ultrasound in 19 patients with autosomal dominant polycystic kidney disease (ADPKD) and in 19 control patients. The monitoring was performed along the forearm part of the vein, the maximal diameter was measured. The diameters of the two needle insertion sites were also measured.Study II: Nineteen patients were investigated with echocardiography, using M-mode recordings and measurements in the 2D image. Ultrasound and doppler ultrasound were performed. Transsonic measurements were performed after the ultrasound investigation. Measurements of the diameter of the AVF were performed in four locations. Heart variables were analysed regarding left ventricular (LV) criteria.Study III: Thirty patients with native AVF in the forearm were included. Each patient was his/her own control. Ultrasound examinations of the AVF diameter and blood flow velocity were performed before and after a single Far Infrared light (FIR) treatment.Study IV: 522 radiological investigations and endovascular treatments between January 1, 2006 and December 31, 2014 were analysed in 174 patients, retrospectively. All investigations had been performed due to clinical suspicion of impaired AVF function. All stenoses were evaluated and the number, degree, length, location and relation to anastomosis were recorded. After PTA the remaining stenoses were evaluated again and complications were recorded.ResultsStudy I: The diameter of the AVF at the maximal site in patients with ADPKD was significantly wider than that for the control patients.Study II: A larger AVF mean and maximal diameter worsened left ventricular characteristics.Study III: A single FIR treatment resulted in a significant increase in blood velocity over the AV fistula from a mean of 2.1±1.0 m/s to 2.3±1.0 m/s. The diameter of the arterialized vein became wider, i.e. 0.72±0.02 to 0.80±0.02 cm. The increase in fistula blood velocity correlated positively with baseline serum-urate and the increase in venous diameter correlated positively with the baseline plasma orosomucoid concentration.Study IV: The degree of AVF stenosis before PTA correlated significantly with the degree of remaining stenosis after intervention. Arterial stenosis was significantly more frequent among patients with diabetic nephropathy and interstitial nephritis. A shorter life span between PTAs was related to diabetic nephropathy.ConclusionsStudy I: The receiving veins of AVF in patients with ADPKD have an abnormality that causes a greater than normal dilatation in response to the arterialization.Study II: The maximal diameter of the distal AVF seems to be a sensitive marker of LV impairment in stable haemodialysis patients.Study III: A single FIR treatment increased AVF blood velocity and vein diameter. Thus, one FIR treatment can help maturation of AVF in the early postoperative course.Study IV: Repeated PTA was performed significantly more often in patients with diabetic nephropathy. Clinically significant stenosis should be dilated as soon as possible. Occlusion of the AVF should be thrombolyzed and/or dilated when diagnosed.
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| 15. |
- Jerndal, Hanna, PhD-student, et al.
(author)
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WCN23-0624 acute kidney injury and covid-19
- 2023
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In: Kidney International Reports, Supplements. - : Elsevier. - 2468-0249. ; 8:3, s. S438-S438
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Journal article (peer-reviewed)abstract
- Introduction: COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This emerging disease has become a public health emergency worldwide.Acute Kidney Injury (AKI) secondary to COVID-19 has been described in different studies, but information characterising patients with subsequent AKI is limited. The cause of kidney involvement in COVID-19 is thought to be multifactorial. Cardiovascular comorbidity and predisposing factors (e.g. sepsis and nephrotoxins) are considered as important contributors. The tubular damage has been linked to the cytopathic effects of kidney-resident cells and cytokine storm syndrome. To gain better understanding of the effect of COVID-19 on renal function, large clinical and register based studies have been requested.The objective of this study was to quantify the risk of acute kidney injury during and after covid-19.Methods: This was a Swedish prospective cohort study where Generalised Estimating Equation methods (GEE) was used to map the kinetics of kidney injury markers such as serum-creatinine (s-creatinine), cystatin and eGFR for the hospitalised patients in the cohort, comparing patients with moderate and severe COVID-19 during and after the acute infection. Furthermore, we will investigate if patients with kidney dysfunction during COVID-19 have more severe disease outcome compared with the whole cohort, adjusting for age, sex, and comorbidities. We will also compare start values of kidney injury markers with the latest values and count the percentage worsening among all disease severity groups.Cohort: Approximately 550 COVID-19 patients were recruited to the study following informed and signed consent at 2 Swedish University Hospitals. A case report form was filled in at pre-specified time points, and samples collected consecutively. A database was then created containing dates and information regarding symptoms, laboratory samples, complications, and disease severity (e.g., need of oxygen, intensive care, mechanical ventilation, death).Results: There was a significant increase in s-creatinine among hospitalised and intensive care unit patients (n=126) during the acute phase of COVID-19 (day 0-6 post disease onset) when compared to the follow up samples after 90 days from disease onset. There was also a decrease in s-creatinine in day 11-21 and 31-70 among hospitalised and intensive care unit COVID-19 patients when compared to the same follow up samples. This analysis was adjusted for age and sex. See figure 1.Conclusions: Our preliminary results show that s-creatinine was increased during the first days of COVID-19 followed by decreased levels compared to baseline.The higher levels of s-creatinine day 0-6 of COVID-19 could be an effect of the acute infection, but it could also be caused by other factors such as dehydration or medication. The lower levels of s-creatinine might be caused by dietary changes or loss of muscle mass due to immobilisation during hospitalisation. Knowledge about fluctuations in s-creatinine in COVID-19 patients may be of use for treating physicians.
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| 16. |
- Kuklin, Vladimir, et al.
(author)
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Influence of therapeutic plasma exchange treatment on short-term mortality of critically ill adult patients with sepsis-induced organ dysfunction : a systematic review and meta-analysis
- 2024
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In: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 28:1
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Research review (peer-reviewed)abstract
- Introduction: The impact of therapeutic plasma exchange (TPE) on short-term mortality in adult patients with sepsis-induced organ dysfunction remains uncertain. The objective of the study is to assess the effect of adjunct TPE in this setting through a comprehensive literature review.Methods: The National Library of Medicine’s Medline, Ovid (Embase), the Cochrane Library database and clinicaltrial.gov from January 01, 1966, until October 01, 2022, were searched for terms: therapeutic plasma exchange, plasmapheresis, sepsis, and septic shock. We reviewed, selected and extracted data from relevant randomized clinical trials (RCTs) and matched cohort studies (MCSs) comparing short-term mortality in critically ill adult septic patients treated with standard therapy versus those receiving adjunct TPE. Risk of bias was assessed in the RCTs using Cochrane Collaboration tool and in MCSs using ROBINS-I tool. Summary statistics, risk ratios (RRs), and confidence intervals (CIs) were calculated using random effects model.Results: This systematic review included 937 adult critically ill septic patients from five RCTs (n = 367) and fifteen MCSs (n = 570). Of these total, 543 received treatment with TPE in addition to standard care. The meta-analysis includes all five RCTs and only six MCSs (n = 627). The adjunct TPE treatment (n = 300) showed a significant reduction in short-term mortality (RR 0.59, 95% CI 0.47–0.74, I2 3%) compared to standard therapy alone (n = 327). The systematic review of all 20 trials revealed that adding TPE to the standard therapy of critically ill septic patients resulted in faster clinical and/or laboratory recovery.Conclusions: Our comprehensive and up-to-date review demonstrates that adjunct TPE may provide potential survival benefits when compared to standard care for critically ill adult patients with sepsis-induced organ dysfunction. While results of this meta-analysis are encouraging, large well-designed randomized trials are required to identify the optimal patient population and TPE procedure characteristics prior to widespread adoption into practice.
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| 17. |
- Ljungman, Susanne, 1942, et al.
(author)
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Retraining for prevention of peritonitis in peritoneal dialysis patients: A randomized controlled trial
- 2020
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In: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608 .- 1718-4304. ; 40:2, s. 141-152
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Journal article (peer-reviewed)abstract
- Background: Peritonitis is more common in peritoneal dialysis (PD) patients nonadherent to the PD exchange protocol procedures than in compliant patients. We therefore investigated whether regular testing of PD knowledge with focus on infection prophylaxis could increase the time to first peritonitis (primary outcome) and reduce the peritonitis rate in new PD patients. Methods: This physician-initiated, open-label, parallel group trial took place at 57 centers in Sweden, Denmark, Norway, Finland, Estonia, Latvia, the Netherlands, and the United Kingdom from 2010 to 2015. New peritonitis-free PD patients were randomized using computer-generated numbers 1 month after the start of PD either to a control group (n = 331) treated according to center routines or to a retraining group (n = 340), which underwent testing of PD knowledge and skills at 1, 3, 6, 12, 18, 24, 30, and 36 months after PD start, followed by retraining if the goals were not achieved. Results: In all, 74% of the controls and 80% of the retraining patients discontinued the study. The groups did not differ significantly regarding cumulative incidence of first peritonitis adjusted for competing risks (kidney transplantation, transfer to hemodialysis and death; hazard ratio 0.84; 95% confidence interval (CI) 0.65-1.09) nor regarding peritonitis rate per patient year (relative risk 0.93; 95% CI 0.75-1.16). Conclusions: In this randomized controlled trial, we were unable to demonstrate that regular, targeted testing and retraining of new PD patients increased the time to first peritonitis or reduced the rate of peritonitis, as the study comprised patients with a low risk of peritonitis, was underpowered, open to type 1 statistical error, and contamination between groups.
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| 18. |
- Mölne, Johan, et al.
(author)
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Glomerular macrophage index (GMI) in kidney transplant biopsies is associated with graft outcome
- 2022
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In: Clinical Transplantation. - : John Wiley & Sons. - 0902-0063 .- 1399-0012. ; 36:12
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Journal article (peer-reviewed)abstract
- Background: Macrophages in renal transplants have been shown to participate in antibody-mediated rejection and are associated with impaired renal function. We calculated the glomerular macrophage index (GMI) in a large transplant biopsy cohort, studied its quantity in different diagnostic groups, to clarify its possible impact on graft survival.Methods: GMI, defined as the mean number of macrophages in 10 glomeruli, was prospectively quantified in 1440 renal transplant biopsies over a 10-year period. The main histopathological diagnoses were grouped into eight disease entities, and GMI was compared to normal transplant biopsies as the reference group. The impact of GMI on graft survival was analyzed.Results: GMI was highest in chronic (mean 9.4) and active (9.7) antibody mediated rejections (ABMR), mixed rejections (7.6), and recurrent or de novo glomerulonephritis (7.5) and differed significantly from normal transplants (1.3) in almost all diagnostic groups. Hazard ratios for graft loss were significantly increased for all biopsies with GMI ≥1.9 compared to GMI <.5 (reference group) in an adjusted Cox regression model and increased with higher GMI levels. Biopsies with GMI ≥ 4.6 had < 60% 10-year graft-survival, compared to > 80% with GMI ≤ 1.8.Conclusion: GMI levels were predictive of graft loss independent of histological diagnoses and may guide clinicians to decide follow-up and therapy.
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| 19. |
- Mörtzell Henriksson, Monica, et al.
(author)
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Analyses of registry data of patients with anti-GBM and antineutrophil cytoplasmatic antibody-associated (ANCA) vasculitis treated with or without therapeutic apheresis
- 2021
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In: Transfusion and Apheresis Science. - : Elsevier BV. - 1473-0502 .- 1878-1683. ; 60:6
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Journal article (peer-reviewed)abstract
- Therapeutic apheresis (TA) as a treatment for antibody-associated vasculitis (AAV) was questioned by the PEXIVAS although the MEPEX study favored TA. The aim of this study was to evaluate the efficacy of TA to improve renal function in patients consecutively included in the WAA-apheresis registry versus patients not treated with TA. Materials and methods: Included were 192 patients that suffered from anti-glomerular basement membrane disease (anti-GBM, n = 28) and antineutrophil cytoplasmic antibody-associated vasculitis of MPO or PR3 origin. Of these 119 had performed TA and the other 73 had not performed TA for theses diagnoses (CTRL). Results: Elderly had an increased risk to die within 12 months (p = 0.002). All 28 anti-GBM had renal involvement, 21 dialysis dependent. At 3 month nine (36 %) did not need dialysis. Baseline data regarding renal function of AAV patients, subtype MPO and PR3, were worse in the TA groups than in CTRL. Recovery out of dialysis was better for the PR3-TA group compared with 1) the controls of MEPEX (RR 0.59, CI 0.43−0.80) and 2) the MPO-TA patients (RR 0.28, CI 0.12−0.68). The MPO-TA recovered similarly as the MEPEX-CTRL. Renal function improved most for TA-patients from baseline during the first 3 months (MPO-TA and PR3-TA) and stabilized thereafter and less for MPO-CTRL and PR3-CTRL. Conclusion: PR3-TA patients seem to have best chances to get out of dialysis. PR3-TA and MPO-TA improved residual renal function better than CTRL. The present study recommends reconsiderations to use TA for AAV especially those with PR3-vasculitis with severe renal vasculitis.
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| 20. |
- Nasic, Salmir, et al.
(author)
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Changes in numbers of glomerular macrophages between two consecutive biopsies and the association with renal transplant graft survival
- 2024
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In: Clinical Transplantation. - : John Wiley & Sons. - 0902-0063 .- 1399-0012. ; 38:7
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Journal article (peer-reviewed)abstract
- Background: Macrophages are involved in kidney transplants. The aim of the study was to investigate if changes exist in the levels of glomerular macrophage index (GMI) between two consecutive kidney transplant biopsies, and if so to determine their potential impact on graft survival.Methods: Two consecutive biopsies were performed on the same renal graft in 623 patients. GMI was categorized into three GMI classes: ≤1.8 Low, 1.9–4.5 Medium, and ≥4.6 High. This division yielded nine possible switches between the first and second biopsies (Low-Low, Low-Medium, etc.). Cox-regressions were used and hazard ratios (HR) with 95% confidence interval (CI) are presented.Results: The worst graft survival was observed in the High-High group, and the best graft survival was observed in the Low-Low and High-Low groups. Compared to the High-High group, a reduction of risk was observed in nearly all other decreasing groups (reductions between 65% and 80% of graft loss). After adjustment for covariates, the risk for graft-loss was lower in the Low-Low (HR = 0.24, CI 0.13–0.46), Low-Medium (HR = 0.25, CI 0.11–0.55), Medium-Low (HR = 0.29, CI 0.11–0.77), and the High-Low GMI (HR = 0.31, CI 0.10–0.98) groups compared to the High-High group as the reference.Conclusions: GMI may change dynamically, and the latest finding is of most prognostic importance. GMI should be considered in all evaluations of biopsy findings since high or increasing GMI levels are associated with shorter graft survival. Future studies need to consider therapeutic strategies to lower or maintain a low GMI. A high GMI besides a vague histological finding should be considered as a warning sign requiring more frequent clinical follow up.
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| 21. |
- Nasic, Salmir, et al.
(author)
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Histological diagnosis from kidney transplant biopsy can contribute to prediction of graft survival
- 2022
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In: Nephrology. - : Wiley. - 1320-5358 .- 1440-1797. ; 27:6, s. 528-536
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Journal article (peer-reviewed)abstract
- Aim The primary aim of this study was to in depth examine if the histological findings in a transplanted kidney biopsy can predict the prognosis for the graft and the patient. The secondary aim was to extend knowledge of the impact of time elapsed on biopsy findings. Methods Data from 1462 patients were merged from a kidney transplantation registry and a biopsy registry during 1 January 2007 and 30 September 2017. Kaplan-Meier analysis and multivariate Cox-regression analysis were performed and hazard ratios (HR) with 95% confidence intervals (CI) were presented. Results Compared to normal biopsy findings, graft survival after biopsy (gsaBiopsy) was shorter for patients with glomerular diseases (HR 8.2, CI:3.2-21.1), rejections (HR 4.2, CI:1.7-10.3), chronic changes including IFTA (HR 3.2, CI:1.3-8.0), acute tubular injuries (HR 3.0, CI:1.2-7.8), and borderline changes (HR 2.9, CI:1.1-7.6). Sub-analysis of rejections showed shorter gsaBiopsy for chronic TCMR (HR 4.7, CI:1.9-11.3), active ABMR (HR 3.6, CI:1.7-7.7) and chronic ABMR (HR 3.5, CI:2.0-6.0). Patients with TCMR Banff grade II (HR 0.35, CI:0.20-0.63) and grade I (HR 0.52, CI:0.29-0.93) had a better gsaBiopsy compared to all other types of rejections. Conclusion Shorter gsaBiopsy was noted in kidneys with glomerular diseases, rejections, acute tubular injuries and borderline changes. TCMR Banff rejections grade I and II were associated with a better prognosis.
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| 22. |
- Nasic, Salmir, et al.
(author)
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Sex-specific time trends of long-term graft survival after kidney transplantation : a registry-based study
- 2023
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In: Renal failure. - : Taylor & Francis. - 0886-022X .- 1525-6049. ; 45:2
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Journal article (peer-reviewed)abstract
- Background: Sex-specific trends over time with respect to kidney graft survival have scarcely been described in earlier studies. The present study aimed to examine whether kidney graft survival differs between women and men over time.Methods: This study was based on prospectively collected data extracted from a quality registry including all kidney transplant patients between January 1965 and September 2017 at the transplantation center of a university hospital in Sweden. The transplantation center serves a population of approximately 3.5 million inhabitants. Only the first graft for each patient was included in the study resulting in 4698 transplantations from unique patients (37% women, 63% men). Patients were followed-up until graft failure, death, or the end of the study. Death-censored graft survival analysis after kidney transplantation (KT) was performed using Kaplan-Meier analysis with log-rank test, and analysis adjusted for confounders was performed using multivariable Cox regression analysis.Results: Median age at transplantation was 48 years (quartiles 36–57 years) and was similar for women and men. Graft survival was analyzed separately in four transplantation periods that represented various immunosuppressive regimes (1965-1985, 1986–1995, 1996–2005, and 2006–2017). Sex differences in graft survival varied over time (sex-by-period interaction, p = 0.026). During the three first periods, there were no significant sex differences in graft survival. However, during the last period, women had shorter graft survival (p = 0.022, hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.1–2.7, adjusted for covariates). Biopsy-proven rejections were more common in women.Conclusions: In this registry-based study, women had shorter graft survival than men during the last observation period (years 2006–2017).
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| 23. |
- Nilsson, Christina, et al.
(author)
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A surgical girdle postoperatively may prevent pain and tunnel infections of peritoneal dialysis patients
- 2020
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In: International Journal of Artificial Organs. - : Sage Publications. - 0391-3988 .- 1724-6040. ; 43:4, s. 225-228
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Journal article (peer-reviewed)abstract
- Aim: When performing acute onset dialysis after insertion of catheters for peritoneal dialysis, pain exists and tunnel infections may develop. This study investigated whether patients benefit from the use of a surgical girdle and specific dressing postoperatively to prevent pain and tunnel infections.Materials and Methods: In 85 consecutive patients, the development of tunnel infections was followed. The patients used a surgical girdle when they were in supine position from day 1 to day 3. The peritoneal dialysis catheter was fixed in a curvature avoiding stretch in the exit. A total of 53 patients participated in a retrospective questionnaire to evaluate abdominal pain within the first 3 days after surgery either with or without girdle. A visual analogue scale from 0 to 10 was used.Results: In 23 patients, data on pain both with and without the girdle could be recorded. Pain was relieved more when using the girdle versus no girdle (median day 1 3.0 vs 4.0, p < 0.001, n = 30, Wilcoxon paired). The development of tunnel infections during the latest 7-year period (exposure period 1487 months) showed a total of three episodes (one every 495 months) of which one caused a subsequent peritonitis, while the other two resolved after antibiotic therapy. Peritonitis episodes appeared at a mean of 37-month interval.Conclusion: The use a surgical girdle for 3 days postoperatively and a fixation of the peritoneal dialysis catheter in a curved loop relieves the pain and results in few tunnel infections and subsequent episodes of peritonitis.
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| 24. |
- Peters, Björn, et al.
(author)
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Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy
- 2023
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In: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 38:12, s. 2826-2834
-
Journal article (peer-reviewed)abstract
- 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.
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| 25. |
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| 26. |
- Peters, Björn, et al.
(author)
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Renal transplant biopsy complications: assessment of risk factors and potential of desmopressin to decrease risk of hemorrhage
- 2020
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In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 61:12, s. 1717-1723
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Journal article (peer-reviewed)abstract
- Background Renal transplant biopsies are essential in nephrology; however, they are invasive and complications can occur. Purpose To explore the risk of transplant kidney biopsy (TxB) complications in relation to possible preventive effects of desmopressin prophylaxis. Material and Methods A total of 515 consecutive TxB (375 patients, median age 53 years) were analyzed. In 252 TxB, the Resistive Index (RI) was measured right before the biopsy. A total of 282 patients had serum creatinine >150 mu mol/L. In one of the six hospitals 39/282 patients consecutively received desmopressin (dose 0.3 mu g/kg subcutaneously) as prophylaxis within 1 h before the biopsy. Fisher's exact and chi(2) test were used (odds ratio [OR], 95% confidence interval [CI]). Univariate and multiple binary logistic regression analyses were performed. A two-sided P value Results RI >= 0.8 was a risk factor for major TxB complications (OR 4.2, 95% CI 1.13-15.76). The risk for minor complications decreased with mean arterial blood pressure (MAP) (97.9 vs. 89.5 mmHg, OR 0.97, 95% CI 0.95-0.997). In a multiple regression analysis for overall biopsy complications, the risk remained increased for patients with RI >= 0.8 (OR 4.45, 95% CI 1.32-15.04). No patients (0/39) with desmopressin prophylaxis had a major complication versus 8/243 in the other group. In patients with serum creatinine >150 mu mol/L, those with a higher MAP had more overall TxB complications (104.5 vs. 98.2 mmHg, OR 1.05, 95% CI 1.004-1.1). Conclusion RI >= 0.8 was a risk factor for major and overall complications and a lower MAP for minor biopsy complications. Desmopressin prophylaxis showed yet no verified benefit as prophylaxis in TxB.
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| 27. |
- Rock, Gail, et al.
(author)
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Therapeutic plasma exchange (TPE) as a plausible rescue therapy in severe vaccine-induced immune thrombotic thrombocytopenia
- 2021
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In: Transfusion and apheresis science. - : Elsevier. - 1473-0502 .- 1878-1683. ; 60:4
-
Research review (peer-reviewed)abstract
- Vaccine-induced immune thrombotic thrombocytopenia (VITT) is associated with high titers of immunoglobulin G class antibodies directed against the cationic platelet chemokine platelet factor 4 (PF4). These antibodies activate platelets via FcγIIa receptors. VITT closely resembles heparin-induced thrombocytopenia. Inflammation and tissue trauma substantially increase the risk for forming pathogenic PF4 antibodies. We therefore propose the use of therapeutic plasma exchange as rescue therapy in VITT to deplete antibodies plus factors promoting inflammation such as excess cytokines in the circulation as well as extracellular vesicles derived from activated platelets.
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| 28. |
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| 29. |
- Rudnicki, Michael, et al.
(author)
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Urine proteomics for prediction of disease progression in patients with IgA nephropathy
- 2022
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In: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 37:1, s. 42-52
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Journal article (peer-reviewed)abstract
- Background: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification.Methods: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models.Results: Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83-0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64-0.81).Conclusions: A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone.
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| 30. |
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| 31. |
- Siwy, Justyna, et al.
(author)
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CD99 and polymeric immunoglobulin receptor peptides deregulation in critical COVID-19 : A potential link to molecular pathophysiology?
- 2021
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In: Proteomics. - : John Wiley & Sons. - 1615-9853 .- 1615-9861. ; 21:20
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Journal article (peer-reviewed)abstract
- Identification of significant changes in urinary peptides may enable improved understanding of molecular disease mechanisms. We aimed towards identifying urinary peptides associated with critical course of COVID-19 to yield hypotheses on molecular pathophysiological mechanisms in disease development. In this multicentre prospective study urine samples of PCR-confirmed COVID-19 patients were collected in different centres across Europe. The urinary peptidome of 53 patients at WHO stages 6–8 and 66 at WHO stages 1–3 COVID-19 disease was analysed using capillary electrophoresis coupled to mass spectrometry. 593 peptides were identified significantly affected by disease severity. These peptides were compared with changes associated with kidney disease or heart failure. Similarities with kidney disease were observed, indicating comparable molecular mechanisms. In contrast, convincing similarity to heart failure could not be detected. The data for the first time showed deregulation of CD99 and polymeric immunoglobulin receptor peptides and of known peptides associated with kidney disease, including collagen and alpha-1-antitrypsin. Peptidomic findings were in line with the pathophysiology of COVID-19. The clinical corollary is that COVID-19 induces specific inflammation of numerous tissues including endothelial lining. Restoring these changes, especially in CD99, PIGR and alpha-1-antitripsin, may represent a valid and effective therapeutic approach in COVID-19, targeting improvement of endothelial integrity.
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| 32. |
- Skagerlind, Malin, 1975-, et al.
(author)
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An evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis
- 2018
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In: European Journal of Clinical Pharmacology. - : Springer. - 0031-6970 .- 1432-1041. ; 74:3, s. 267-274
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Journal article (peer-reviewed)abstract
- Intensive care participants that need dialysis frequently suffer from increased risk of bleeding. Standard intermittent haemodialysis (SHD) includes anticoagulation to avoid clotting of the dialysis system. The aim of this study was to clarify which of four different low-dose anticoagulant modes was preferable in reducing the exposure to i.v. unfractionated heparin (heparin) and maintaining patency of the dialysis circuit. Twenty-three patients on SHD were included to perform haemodialysis with four modes of low-dose anticoagulation. For comparative analyses, patients served as their own control. Haemodialysis with a single bolus of tinzaparin at the start was compared to haemodialysis initiated without i.v. heparin but priming with (1) heparin in saline (H), (2) heparin and albumin in saline (HA), (3) heparin and albumin in combination with a citrate-containing dialysate (HAC), (4) saline and usinga heparin-coated filters (EvodialA (R)). The priming fluid was discarded before dialysis started. Blood samples were collected at 0, 30 and 180 min during haemodialysis. Smaller bolus doses of heparin (500 Units/dose) were allowed during the modes to avoid interruption by clotting. The mean activated partial thromboplastin (APTT) time as well as the doses of anticoagulation administered was highest with SHD and least with HAC and EvodialA (R). Mode H versus SHD had the highest rate of prematurely interrupted dialyses (33%, p = 0.008). The urea reduction rate was less with EvodialA (R) vs. SHD (p < 0.01). One hypersensitivity reaction occurred with EvodialA (R). Changes in blood cell concentrations and triglycerides differed between the modes. If intermittent haemodialysis is necessary in patients at risk of bleeding, anticoagulation using HAC and EvodialA (R) appeared most preferable with least administration of heparin, lowest APTT increase and lowest risk for prematurely clotted dialyzers in contrast to the least plausible H mode.
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| 33. |
- Stegmayr, Bernd, 1949-, et al.
(author)
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Arteriovenous access in hemodialysis : A multidisciplinary perspective for future solutions
- 2021
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In: International Journal of Artificial Organs. - : Sage Publications. - 0391-3988 .- 1724-6040. ; 44:1, s. 3-16
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Research review (peer-reviewed)abstract
- In hemodialysis, vascular access is a key issue. The preferred access is an arteriovenous fistula on the non-dominant lower arm. If the natural vessels are insufficient for such access, the insertion of a synthetic vascular graft between artery and vein is an option to construct an arteriovenous shunt for punctures. In emergency situations and especially in elderly with narrow and atherosclerotic vessels, a cuffed double-lumen catheter is placed in a larger vein for chronic use. The latter option constitutes a greater risk for infections while arteriovenous fistula and arteriovenous shunt can fail due to stenosis, thrombosis, or infections. This review will recapitulate the vast and interdisciplinary scenario that characterizes hemodialysis vascular access creation and function, since adequate access management must be based on knowledge of the state of the art and on future perspectives. We also discuss recent developments to improve arteriovenous fistula creation and patency, the blood compatibility of arteriovenous shunt, needs to avoid infections, and potential development of tissue engineering applications in hemodialysis vascular access. The ultimate goal is to spread more knowledge in a critical area of medicine that is importantly affecting medical costs of renal replacement therapies and patients’ quality of life.
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| 34. |
- Stegmayr, Bernd G., 1949-, et al.
(author)
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Hemodialysis patients have signs of a chronic thrombotic burden
- 2024
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In: BMC Nephrology. - : BioMed Central (BMC). - 1471-2369. ; 25:1
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Journal article (peer-reviewed)abstract
- Background: Cardiovascular diseases are the dominant cause of morbidity in hemodialysis (HD) patients. Unless sufficient anticoagulation is used during HD, clotting may appear. The objective was to investigate if levels of fibrin degradation products (D-dimer) were increased before and during HD.Methods: The combined observational study included 20 patients performing a total of 60 hemodialysis divided into three sessions of low-flux dialysis. None of the patients suffered from any clinically evident thromboembolic event before or during the study. Median bolus anticoagulation (mainly tinzaparin) doses were 84 Units/kg bow. Blood samples were drawn before HD (predialysis), and at 30min and 180min during HD with focus on analyzing D-dimer levels and its relation to interdialytic weight gain (IDWG) and speed of fluid elimination by HD (UF-rate).Results: Predialysis, D-dimer levels (mean 0.767 ±0.821, min 0.136mg/L) were above the upper reference value in 95% of the sessions. D-dimer levels were lowered at 30min (p<0.001) and returned to predialysis levels at 180min. Predialysis D-dimer correlated with NT-pro-BNP, Troponin T, IDWG and UF-rate. Multiple regression analysis revealed that the D-dimer levels were significantly related to IDWG and the UF-rate.Conclusions: D-dimer levels were elevated in a high proportion predialysis and during HD and related to the IDWG and the UF-rate. Awareness of D-dimer levels and future studies will help clarify if optimization of those variables, besides anticoagulation and biocompatibility measures, will eradicate the repeated subclinical thromboembolic events related to each HD; one reason that may explain organ damage and shortened life span of these patients.
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| 35. |
- Stegmayr, Bernd, 1949-, et al.
(author)
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Lipid and bone effects of heparin use during hemodialysis
- 2024
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In: Seminars in Nephrology. - : Elsevier. - 0270-9295 .- 1558-4488.
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Research review (peer-reviewed)abstract
- Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) are commonly prescribed anticoagulants for chronic hemodialysis (HD). The dialysis population comprises a unique group that receives heparin three times per week for a long period, with potential long-term cumulative metabolic effects such as osteoporosis and worsening lipid profile. HD patients have approximately half the number of lipases as healthy individuals, and their lipid metabolism is limited because of this decrease as well as partially inhibited function. Administration of UFH or LMWHs for anticoagulation can lead to metabolic starvation despite high triglyceride levels at the end of HD. In vitro studies indicate that UFH and LMWHs inhibit osteoblasts and promote osteoclasts. In patients on HD, long-term use of UFH or LMWHs did not worsen chronic kidney disease–mineral bone disease. Further investigation is needed to elucidate the underlining mechanisms of UFH and LMWHs and their possible influences on maintenance HD patients.
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| 36. |
- Stegmayr, Bernd, 1949-, et al.
(author)
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Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis
- 2021
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In: Transfusion Medicine and Hemotherapy. - : S. Karger. - 1660-3796 .- 1660-3818. ; 48:4, s. 234-239
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Research review (peer-reviewed)abstract
- Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. Conclusion: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects. (c) 2021 S. Karger AG, Basel
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| 37. |
- Vollmer, Tino, et al.
(author)
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Establishing Cell Models to Understand Cellular Toxicity: Lessons Learned from an Unconventional Cell Type
- 2022
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In: Toxins. - : MDPI. - 2072-6651. ; 14:1
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Research review (peer-reviewed)abstract
- The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with the expected reactions in human patients and studies on one organ system are limited in capturing the complexity of the uremic situation. In this narrative review, we present aspects relevant for cellular toxicity research based on our previous establishment of a human spermatozoa-based cell model, as follows: (i) applicability to compare the effects of more than 100 uremic substances, (ii) detection of the protective effects of uremic substances by the cellular responses towards the uremic milieu, (iii) inclusion of the drug milieu for cellular function, and (iv) transferability for clinical application, e.g., hemodialysis. Our technique allows the estimation of cell viability, vitality, and physiological state, not only restricted to acute or chronic kidney toxicity but also for other conditions, such as intoxications of unknown substances. The cellular models can clarify molecular mechanisms of action of toxins related to human physiology and therapy. Identification of uremic toxins retained during acute and chronic kidney injury enables further research on the removal or degradation of such products.
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| 38. |
- Vrielink, Hans, et al.
(author)
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The world apheresis association registry, 2023 update
- 2023
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In: Transfusion and apheresis science. - : Elsevier. - 1473-0502 .- 1878-1683. ; 62:6
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Research review (peer-reviewed)abstract
- The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs).Material and Methods: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.orgResults: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018–2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0–94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%).Conclusion: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.
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| 39. |
- Witt, Volker, et al.
(author)
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The WAA-registry
- 2024
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In: Transfusion and apheresis science. - : Elsevier. - 1473-0502 .- 1878-1683.
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Journal article (other academic/artistic)
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| 40. |
- Wärja, Michaela, et al.
(author)
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NT-pro-BNP as marker for cardiac strain that may be caused by high-output arteriovenous shunting in a haemodialysis patient. A case report
- 2020
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In: BMC Nephrology. - : BioMed Central. - 1471-2369. ; 21:1
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Journal article (peer-reviewed)abstract
- Background: An arteriovenous fistula (AVF) is the first choice when considering access for haemodialysis (HD).When a forearm AVF fails an upper arm AVF is a frequent subsequent dialysis access option. The latter may causecardiac strain. NT-pro-B-type natriuretic peptide (NT-NT-proBNP) is a marker used to estimate volume overload andcardiac strain.This case report shows the benefit of using longitudinal individual follow-up of pre-dialysis NT-proBNP in clinicalpractice to detect changes in cardiac condition that may be due to high-output AVF.Case presentation: An 18 years old patient performed HD via an upper arm AVF before he was admitted to ourunit. NT-proBNP was above the upper detection level of 70,000 ng/L. Echocardiography revealed a left-ventricularcardiac insufficiency. Interdialytic weight gain (IDWG) was above 5%. He was instructed to lower fluid intake andIDWG towards 2%. Four months later NT-proBNP surpassed 70,000 ng/L again. Flow in the brachial artery was at3034 ml/min. Reconstructive surgery of the AVF did not reduce flow and NT-proBNP in the long run. Clinically, heworsened to NYHA class III-IV. It was decided to close the upper arm AVF and to replace it with a lower arm AVFleading to a reduced artery flow of 1344 mL/min. The clinical condition successively recovered and NT-proBNPdecreased to 7000 ng/L.Conclusions: Pre-dialysis NT-proBNP should be considered as a suitable routine marker for cardiac strain such ascaused by high-output AVF besides variables such as IDWG. Brachial artery flow besides AVF flow measurement ishelpful.
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| 41. |
- Wärme, Anna, et al.
(author)
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The association of erythropoietin-stimulating agents and increased risk for AV-fistula dysfunction in hemodialysis patients. A retrospective analysis
- 2021
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In: Bmc Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 22
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Journal article (peer-reviewed)abstract
- Background Patients in maintenance hemodialysis (HD) need a patent vascular access for optimal treatment. The recommended first choice is a native arteriovenous fistula (AVF). Complications of AVF are frequent and include thrombosis, stenosis and infections leading to worsening of dialysis efficacy. Some known risk factors are age, gender and the presence of diabetes mellitus. The aim was to investigate if further risk variables are associated with dysfunctional AVF. Methods This retrospective observational study included 153 chronic HD patients (Cases) referred to a total of 473 radiological investigations due to clinically suspected complications of their native AVF. Another group of chronic HD patients (n = 52) who had a native AVF but were without history of previous complications for at least 2 years were controls. Statistical analyses included ANOVA, logistic regression, parametric and non-parametric methods such as Student's T-test and Mann-Whitney test. Results Among Cases, at least one significant stenosis (> 50% of the lumen) was detected in 348 occasions. Subsequent PTA was performed in 248 (71%). Median erythropoiesis-stimulating agent (ESA) weekly doses were higher in Cases than in Controls (8000 vs 5000 IU, p < 0.001). Cases received higher doses of intravenous iron/week than the Controls before the investigation (median 50 mg vs 25 mg, p = 0.004) and low molecular weight heparin (LMWH, p = 0.028). Compared to Controls, Cases had a lower level of parathyroid hormone (median 25 vs 20 rho mol/L, p = 0.009). In patients with diabetes mellitus, HbA1c was higher among Cases than Controls (50 vs 38 mmol/mol, p < 0.001). Multiple regression analysis revealed significant associations between Cases and female gender, prescription of doxazocin, and doses of ESA and LMWH. There was no difference between the groups regarding hemoglobin, CRP or ferritin. Conclusion In conclusion, the present study indicated that the factors associated with AVF problems were high doses of ESA, iron administration, and tendency of thromboembolism (indicated by high LMWH doses); the use of doxazocin prescription, however, requires further investigation.
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