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  • 1.
    de Laval, Philip
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Mobarrez, Fariborz
    Karolinska Univ Hosp, Karolinska Inst, Unit Rheumatol, Dept Med, Solna, Sweden.
    Almquist, Tora
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Nephrol, Stockholm, Sweden.
    Vassil, Liina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Acute effects of haemodialysis on circulating microparticles2019In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 12, no 3, p. 456-462Article in journal (Refereed)
    Abstract [en]

    Background. Microparticles (MPs) are small cell membrane-derived vesicles regarded as both biomarkers and mediators of biological effects. Elevated levels of MPs have previously been associated with endothelial dysfunction and predict cardiovascular death in patients with end-stage renal disease. The objective of this study was to measure change in MP concentrations in contemporary haemodialysis (HD).

    Methods. Blood was sampled from 20 consecutive HD patients before and 1h into the HD session. MPs were measured by flow cytometry and phenotyped based on surface markers.

    Results. Concentrations of platelet (CD41(+)) (P = 0.039), endothelial (CD62E(+)) (P = 0.004) andmonocyte-derived MPs (CD14(+)) (P<0.001) significantly increased during HD. Similarly, endothelial-(P = 0.007) and monocyte-derived MPs (P = 0.001) expressing tissue factor (TF) significantly increased as well as MPs expressing Klotho (P = 0.003) and receptor for advanced glycation end products (RAGE) (P = 0.009). Furthermore, MPs expressing platelet activationmarkers P-selectin (P = 0.009) and CD40L (P = 0.045) also significantly increased. The increase of endothelial (P = 0.034), monocyte (P = 0.014) and RAGE(+) MPs (P = 0.032) as well as TF+ platelet-derived MPs (P = 0.043) was significantly higher in patients treated with low-flux compared with high-flux dialysers.

    Conclusion. Dialysis triggers release of MPs of various origins with marked differences between high-flux and low-flux dialysers. The MPs carry surface molecules that could possibly influence coagulation, inflammation, oxidative stress and endothelial dysfunction. The clinical impact of these findings remains to be established in future studies.

  • 2. Delanaye, Pierre
    et al.
    Ebert, Natalie
    Melsom, Toralf
    Gaspari, Flavio
    Mariat, Christophe
    Cavalier, Etienne
    Björk, Jonas
    Christensson, Anders
    Nyman, Ulf
    Porrini, Esteban
    Remuzzi, Giuseppe
    Ruggenenti, Piero
    Schaeffner, Elke
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Sterner, Gunnar
    Eriksen, Bjørn Odvar
    Bäck, Sten-Erik
    Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1 How to measure glomerular filtration rate with iohexol?2016In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 9, no 5, p. 682-699Article in journal (Refereed)
    Abstract [en]

    While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method.

  • 3. Delanaye, Pierre
    et al.
    Melsom, Toralf
    Ebert, Natalie
    Bäck, Sten-Erik
    Mariat, Christophe
    Cavalier, Etienne
    Björk, Jonas
    Christensson, Anders
    Nyman, Ulf
    Porrini, Esteban
    Remuzzi, Giuseppe
    Ruggenenti, Piero
    Schaeffner, Elke
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Sterner, Gunnar
    Eriksen, Bjørn Odvar
    Gaspari, Flavio
    Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2 Why to measure glomerular filtration rate with iohexol?2016In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 9, no 5, p. 700-704Article in journal (Refereed)
    Abstract [en]

    A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrow therapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the only way to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol plasma clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research.

  • 4. Hilderman, Marie
    et al.
    Qureshi, Abdul R
    Al-Abed, Yousef
    Abtahi, Farhad
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems.
    Lindecrantz, Kaj
    Anderstam, Björn
    Bruchfeld, Annette
    Cholinergic anti-inflammatory pathway activity in dialysis patients: a role for neuroimmunomodulation?2015In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through the vagus nerve and the α-7-nicotinic acetylcholine receptor (α7nAChR) on macrophages and immune cells. Sympathetic/parasympathetic imbalance and chronic inflammation are both linked to poor outcome in dialysis patients. The aim of this study was to investigate CAP activity in these patients.

    METHODS: Twenty dialysis patients, 12 hemodialysis (HD) and 8 peritoneal dialysis (PD) patients (12 male, 8 female; age range 47-83 years) and 8 controls (5 male, 3 female; age range 31-52 years) were analyzed for C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin-1b (IL-1b), IL-6 and IL-10 at baseline. The cytokines were then assessed after whole blood stimulation ex vivo with lipopolysaccharide (LPS) (10 and 100 ng/mL) and again in the presence of 45 and 90 μmol/L GTS-21, a cholinergic α7nAChR agonist.

    RESULTS: CRP, TNF, IL-1 and IL-6 were significantly higher, whereas IL-10 was significantly lower at baseline in patients compared with controls. After LPS stimulation, TNF increased significantly more in patients than in controls but decreased to similar levels in both groups after addition of GTS-21. IL-6 attenuation was comparable with TNF and the IL-1b pattern was similar but remained significantly higher in patients. Interestingly, IL-10 increased after GTS-21 in a dose-dependent manner, but only in patients. Results in HD and PD patients did not differ.

    CONCLUSIONS: The response of immune cells after LPS exposure and cholinergic stimulation suggests a functional CAP in dialysis patients. It may thus be possible to target the α7nAChR control of cytokine release as an anti-inflammatory strategy and thereby improve outcome in these patients.

  • 5.
    Huang, Shan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Anders
    Gambro Lundia AB.
    Wieslander, Anders
    Gambro Lundia AB.
    Grundström, Gunilla
    Gambro Lundia AB.
    Hancock, Viktoria
    Gambro Lundia AB.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Low concentrations of citrate reduce complement and granulocyte activation in vitro in human blood2015In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 1, p. 31-37Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:The use of acetate in haemodialysis fluids may induce negative effects in patients including nausea and increased inflammation. Therefore, haemodialysis fluids where acetate is substituted with citrate have recently been developed. In this study, we investigated the biocompatibility of citrate employing concentrations used in haemodialysis.

    METHODS:The effects of citrate and acetate were investigated in human whole blood in vitro under conditions promoting biomaterial-induced activation. Complement activation was measured as generation of C3a, C5a and the sC5b-9 complex, and granulocyte activation as up-regulation of CD11b expression. For the experimental set-up, a mathematical model was created to calculate the concentrations of acetate and citrate attained during haemodialysis.

    RESULTS:Citrate reduced granulocyte activation and did not induce higher complement activation compared with acetate at concentrations attained during haemodialysis. Investigating different citrate concentrations clearly showed that citrate is a potent complement inhibitor already at low concentrations, i.e. 0.25 mM, which is comparable with concentrations detected in the blood of patients during dialysis with citrate-containing fluids. Increased citrate concentration up to 6 mM further reduced the activation of C3a, C5a and sC5b-9, as well as the expression of CD11b.

    CONCLUSIONS:Our results suggest that citrate is a promising substitute for acetate for a more biocompatible dialysis, most likely resulting in less adverse effects for the patients.

  • 6. Huang, Shan
    et al.
    Sandholm, Kerstin
    Jonsson, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nilsson, Anders
    Wieslander, Anders
    Grundström, Gunilla
    Hancock, Viktoria
    Nilsson Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Low concentrations of citrate reduce complement and granulocyte activation in vitro in human blood2015In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 1, p. 31-37Article in journal (Refereed)
    Abstract [en]

    Background The use of acetate in haemodialysis fluids may induce negative effects in patients including nausea and increased inflammation. Therefore, haemodialysis fluids where acetate is substituted with citrate have recently been developed. In this study, we investigated the biocompatibility of citrate employing concentrations used in haemodialysis.

    Methods The effects of citrate and acetate were investigated in human whole blood in vitro under conditions promoting biomaterial-induced activation. Complement activation was measured as generation of C3a, C5a and the sC5b-9 complex, and granulocyte activation as up-regulation of CD11b expression. For the experimental set-up, a mathematical model was created to calculate the concentrations of acetate and citrate attained during haemodialysis.

    Results Citrate reduced granulocyte activation and did not induce higher complement activation compared with acetate at concentrations attained during haemodialysis. Investigating different citrate concentrations clearly showed that citrate is a potent complement inhibitor already at low concentrations, i.e. 0.25 mM, which is comparable with concentrations detected in the blood of patients during dialysis with citrate-containing fluids. Increased citrate concentration up to 6 mM further reduced the activation of C3a, C5a and sC5b-9, as well as the expression of CD11b.

    Conclusions Our results suggest that citrate is a promising substitute for acetate for a more biocompatible dialysis, most likely resulting in less adverse effects for the patients.

  • 7.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Nasic, Salmir
    Segelmark, Mårten
    Clinical parameters predicting complications in native kidney biopsies2019In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, article id sfz132Article in journal (Refereed)
    Abstract [en]

    Background

    Renal biopsies are essential in nephrology but they are invasive and complications can occur. The aim of this study was to explore clinical parameters that can be used as predictors for biopsy complications.

    Methods

    Clinical parameters such as demographics, biopsy indications, serology, comorbidities and clinical chemistry were retrieved from a regional biopsy registry between 2006 and 2015 and from a nationwide registry between 2015 and 2017. Clinical data before biopsy were compared with data on major biopsy complications. Fisher’s exact and χ2 tests were used and odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Univariate and multiple binary logistic regression analyses were performed with complications as outcome. A two-sided P-value <0.05 was considered significant.

    Results

    In total, 2835 consecutive native kidney biopsies were analysed (39% women and 61% men, median age 57 years). No death and nephrectomy due to biopsy complications were registered. The frequency of major biopsy complications was 5.65%. In the multiple logistic regression, the risk for complications increased in women [OR 1.51 (95% CI 1.08–2.11)] and decreased with age: 45–64 years age group [OR 0.66 (95% CI 0.44–0.99)] and >74 years age group [OR 0.51 (95% CI 0.27–0.96)]. Among comorbidities, patients with diabetes mellitus type 2 [OR 2.07 (95% CI 1.15–3.72)] and non-ischaemic heart disease [OR 3.20 (95% CI 1.64–6.25)] had a higher risk for major biopsy complications.

    Conclusions

    Female gender, younger age (≤44 years), diabetes mellitus type 2 and non-ischaemic heart disease were found as risk factors for major biopsy complications.

  • 8.
    Segelmark, Mårten
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Dahlberg, Per
    Department of Medicine, NÄL Hospital, Trollhättan, Sweden.
    Wieslander, Jörgen
    Eurodiagnostica AB, Malmö, Sweden.
    Anti-GBM disease with a mild relapsing course and low levels ofanti-GBM autoantibodies2012In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 5, no 6, p. 549-551Article in journal (Refereed)
    Abstract [en]

    Anti-glomerular basement membrane disease (anti-GBM) is usually characterized by rapidly progressive glomerulonephritis, and when autoantibody production has ceased, relapses are rare. Here, we report a 71-year-old women diagnosed at a stage of mild renal insufficiency. Over a period of 10 years, she experienced three mild relapses with return of anti-GBM antibodies, haematuria and slight elevations in serum creatinine level. All three relapses responded to immunosuppressive therapy, and all were preceded by peaks of myeloperoxidase-antineutrophil cytoplasm antibodies (MPO-ANCA). This case shows that long-term follow-up is warranted in patients treated for anti-GBM-mediated disease, but urinary dipsticks may be sufficient for early detection of relapses.

  • 9.
    Xu, Hong
    et al.
    Karolinska institutet .
    Huang, Xiaoyan
    Karolinska institutet; Peking University Shenzhen Hospital.
    Risérus, Ulf
    Uppsala universitet.
    Cederholm, Tommy
    Uppsala universitet.
    Sjögren, Per
    Uppsala universitet.
    Lindholm, Bengt
    Karolinska institutet .
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Carrero, Juan Jesús
    Karolinska institutet .
    Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study2015In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 5, p. 560-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men.

    METHODS: This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression).

    RESULTS: UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m(2)) in its association with the changes of both night-time systolic BP (SBP) and night-day SBP ratio. After stratification, UAER strongly predicted night-day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER.

    CONCLUSIONS: UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations.

  • 10. Xu, Hong
    et al.
    Huang, Xiaoyan
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Carrero, Juan Jesús
    Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study2015In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 5, p. 560-566Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men.

    METHODS: This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression).

    RESULTS: UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m(2)) in its association with the changes of both night-time systolic BP (SBP) and night-day SBP ratio. After stratification, UAER strongly predicted night-day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER.

    CONCLUSIONS: UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations.

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