| 1. |
- Carlsson, Axel C, et al.
(författare)
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Endostatin, cathepsin S, and cathepsin L, and their association with inflammatory markers and mortality in patients undergoing hemodialysis
- 2015
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Ingår i: Blood Purification. - : S. Karger AG. - 0253-5068 .- 1421-9735. ; 39:4, s. 259-265
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Although both endostatin and cathepsins S have been associated with higher mortality, data in patients with end-stage renal disease (ESRD) are scarce.Methods: A longitudinal cohort study of 207 prevalent patients undergoing hemodialysis.Results: Cathepsins S and L were associated with soluble receptors for tumor necrosis factor (sTNFR1 and sTNFR2, rho between 0.28 and 0.43, p < 0.001 for all). Weaker or absent associations between endostatin, cathepsins S and L were seen with other inflammatory biomarkers, that is, CRP, interleukin 6, pentraxin 3, and TNF. In Cox and Laplace regression models adjusted for age, sex, dialysis vintage, and diabetes: standard deviation increments of endostatin was associated with a lower mortality (hazard ratio 0.75, 95% confidence interval (CI) 0.57-0.98), and with 6.8 months longer median survival.Conclusions: The high levels of endostatin, cathepsins S and L, and their associations with sTNFR1 and sTNFR2 warrant further studies exploring mortality, and the angiogenic and inflammatory pathways in ESRD. (C) 2015 S. Karger AG, Basel
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| 2. |
- Carlsson, Axel C, et al.
(författare)
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High levels of soluble tumor necrosis factor receptors 1 and 2 and their association with mortality in patients undergoing hemodialysis
- 2015
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Ingår i: CardioRenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 5:2, s. 89-95
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Circulating soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and 5TNFR2) are associated with chronic kidney disease (CKD) progression in patients with CKD or diabetes, and with higher mortality. However, data in patients with end-stage renal disease are scarce. Therefore, we analyzed serum levels of sTNFR1 and sTNFR2 and investigated their association with inflammatory markers and mortality in dialysis patients. Research Design and Methods: This was a longitudinal cohort study of 207 prevalent patients (median age 66 years, 56% men) undergoing hemodialysis in Stockholm, Sweden. Demographics, clinical characteristics, including comorbidities and laboratory data, were obtained at baseline, together with prospective follow-up for mortality.Results: The median sTNFR1 and sTNFR2 levels were 17,680 ng/l [95% confidence interval (CI) 17,023-18,337] and 24,450 ng/l (95% CI 23,721-25,179), respectively. During a follow-up of 31 months (interquartile range, 21-38), 77 patients died. There was no association between the levels of sTNFRs and mortality in Cox regression models, and no consistent trend towards higher or lower mortality was seen in Laplace regression models. sTNFR1 and sTNFR2 levels were highly associated with other inflammatory markers including interleukin-6, pentraxin 3 and TNF-alpha. Conclusions:Prevalent hemodialysis patients have several-fold higher levels of sTNFRs compared to previous studies in CKD stage 4 patients. As no consistent association between TNFR and mortality was observed, clinical implications of measuring these receptors to predict outcome end-stage renal disease patients provide limited results.
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| 3. |
- Carrero, J.J., et al.
(författare)
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Telomere attrition is associated with inflammation, low fetuin : A levels and high mortality in prevalent haemodialysis patients
- 2008
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 263:3, s. 302-312
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Chronic kidney disease (CKD) predisposes to a 10- to 20-fold increased cardiovascular risk. Patients undergo accelerated atherogenesis and vascular ageing. We investigated whether telomere attrition, a marker of cell senescence, contributes to this increased mortality risk. METHODS: This is a cross-sectional study in prevalent haemodialysis patients [n = 175; 98 Males; median (range) age: 66 (23-86) years]. Biochemical markers of oxidative stress and inflammatory status were measured in relation to the patient's leucocyte telomere length. Overall mortality was assessed after a median of 31 (range 2-42) months. RESULTS: Telomere length was shorter in CKD men, despite women being older (average +/- SD 6.41 +/- 1.23 vs. 6.96 +/- 1.48 kb, P = 0.002). Telomere length was associated with age (rho = -0.18, P = 0.01), fetuin-A (rho = 0.26, P = 0.0004), high-sensitivity C-reactive protein (rho = -0.21, P = 0.005) and IL-6 (rho = -0.17, P = 0.02). In a multivariate logistic regression (pseudo r(2) = 0.14), telomere length was associated with age >65 years (odds ratio: 2.11; 95% CI: 1.10, 4.06), sex (2.01; 1.05, 3.86), fetuin-A (1.85; 0.97, 3.50) and white blood cell count (2.04; 1.02, 4.09). Receiver operating characteristic curves identified a telomere length < 6.28 kb as a fair predictor of mortality. Finally, reduced telomere length was associated with increased mortality, independently of age, gender and inflammation (likelihood ratio 41.6, P < 0.0001), but dependently on fetuin-A levels. CONCLUSION: Age and male gender seem to be important contributors to reduced telomere length in CKD patients, possibly via persistent inflammation. Reduced telomere length also contributes to the mortality risk of these patients through pathways that could involve circulating levels of fetuin-A.
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| 4. |
- Golembiewska, Edyta, et al.
(författare)
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Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5
- 2020
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Ingår i: BMC Nephrology. - Stockholm : Karolinska Institutet, Dept of Clinical Science, Intervention and Technology. - 1471-2369.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30– 70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5. Methods: Copeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n = 43) or hemodialysis (HD) (n = 53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n = 137) and by coronary artery calcification (CAC) score measured by computed tomography. Results: Patients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman’s rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho = 0.27; p = 0.003) and presence of medial VC (Rho = 0.21; p = 0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC. Conclusions: High circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.
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| 5. |
- Hernandez, Leah, et al.
(författare)
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Blood-brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Kidney failure and associated uraemia have implications for the cardiovascular system, brain, and blood-brain barrier (BBB). We aim to examine BBB disruption, by assessing brain-derived neurotropic factor (BDNF), neuron-specific enolase (NSE) levels, and gut-blood barrier (GBB) disruption by trimethylamine N-oxide (TMAO), in chronic kidney disease (CKD) patients. Additionally, endothelial tight-junction protein expressions and modulation via TMAO were assessed. Serum from chronic kidney disease (CKD) female and male haemodialysis (HD) patients, and controls, were used to measure BDNF and NSE by enzyme-linked immunosorbent assays, and TMAO by mass spectrometry. Immunofluorescent staining of subcutaneous fat biopsies from kidney transplant recipients, and controls, were used to measure microvascular expression of tight-junction proteins (claudin-5, occludin, JAM-1), and control microvasculature for TMAO effects. HD patients versus controls, had significantly lower and higher serum levels of BDNF and NSE, respectively. In CKD biopsies versus controls, reduced expression of claudin-5, occludin, and JAM-1 were observed. Incubation with TMAO significantly decreased expression of all tight-junction proteins in the microvasculature. Uraemia affects BBB and GBB resulting in altered levels of circulating NSE, BDNF and TMAO, respectively, and it also reduces expression of tight-junction proteins that confer BBB maintenance. TMAO serves as a potential candidate to alter BBB integrity in CKD.
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| 6. |
- Huang, Xiaoyan, et al.
(författare)
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Essential polyunsaturated fatty acids, inflammation and mortality in dialysis patients
- 2012
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 27:9, s. 3615-3620
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Tidskriftsartikel (refereegranskat)abstract
- Background. Polyunsaturated fatty acids (PUFA) are essential nutrients with anti-inflammatory and cardioprotective properties. We investigated the association of essential dietary PUFA intake, reflected by plasma fatty acid composition, with inflammation and mortality in dialysis patients.Methods. We recruited 222 Swedish dialysis subjects (39% women) with median age of 57 years and average 12 months of dialysis vintage. Plasma phospholipid PUFA were assessed by gas-liquid chromatography. Overall mortality was assessed after 18.4 (10th-90th percentiles: 2.3-60) months of follow-up.Results. Linoleic acid (LA), Mead acid (MA), alpha-linolenic acid (ALA) and long-chain n-3 PUFA (LC n-3; the sum of eicosapentaenoic, docosapentaenoic and docosahexaenoic acids) represented 19.7, 0.26, 0.26 and 7.64% of all fatty acids in plasma, respectively. This may reflect an adequate n-3 PUFA intake. LA was negatively (beta = -0.21, P = 0.004) but MA positively (beta = 0.25, P < 0.001) associated with interleukin (IL)-6 in multivariate analyses. Neither ALA nor LC n-3 were independently associated with IL-6. During follow-up, 61 deaths and 115 kidney transplants occurred. Fully adjusted competing risk models showed that every percent increase in the proportion of plasma LA was associated with 12% reduction in mortality risk before transplantation (hazard ratio 0.88, 95% confidence interval 0.79-0.99). MA was directly associated with mortality. Neither ALA nor LC n-3 predicted outcome.Conclusions. The proportion of plasma phospholipid LA is inversely associated with IL-6 and all-cause mortality in Swedish dialysis patients. We raise the hypothesis that dialysis patients could benefit from increased intake of vegetable oils, the primary source of LA in the Western-type diet.
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| 7. |
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| 8. |
- Isoyama, Naohito, et al.
(författare)
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Comparative Associations of Muscle Mass and Muscle Strength with Mortality in Dialysis Patients
- 2014
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Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 9:10, s. 1720-1728
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives Reduced muscle mass and strength are prevalent conditions in dialysis patients. However, muscle strength and muscle mass are not congruent; muscle strength can diminish even though muscle mass is maintained or increased. This study addresses phenotype and mortality associations of these muscle dysfunction entities alone or in combination (i.e., concurrent loss of muscle mass and strength/mobility, here defined as sarcopenia). Design, setting, participants, & measurements This study included 330 incident dialysis patients (203 men, mean age 53 +/- 13 years, and mean GFR 7 +/- 2 ml/min per 1.73 m(2)) recruited between 1994 and 2010 and followed prospectively for up to 5 years. Low muscle mass (by dual-energy x-ray absorptiometry appendicular mass index) and low muscle strength (by handgrip) were defined against young reference populations according to the European Working Group on Sarcopenia in Older People. Results Whereas 20% of patients had sarcopenia, low muscle mass and low muscle strength alone were observed in a further 24% and 15% of patients, respectively. Old age, comorbidities, protein-energy wasting, physical inactivity, low albumin, and inflammation associated with low muscle strength, but not with low muscle mass (multivariate ANOVA interactions). During follow-up, 95 patients (29%) died and both conditions associated with mortality as separate entities. When combined, individuals with low muscle mass alone were not at increased risk of mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [95% CI] 0.56 to 2.67). Individuals with low muscle strength were at increased risk, irrespective of their muscle stores being appropriate (HR, 1.98; 95% CI, 1.01 to 3.87) or low (HR, 1.93; 95% CI, 1.01 to 3.71). Conclusions Low muscle strength was more strongly associated with aging, protein-energy wasting, physical inactivity, inflammation, and mortality than low muscle mass. Assessment of muscle functionality may provide additional diagnostic and prognostic information to muscle-mass evaluation.
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| 9. |
- Jia, Ting, et al.
(författare)
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Determinants of Fibroblast Growth Factor-23 and Parathyroid Hormone Variability in Dialysis Patients
- 2013
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Ingår i: American Journal of Nephrology. - : Karger. - 0250-8095 .- 1421-9670. ; 37:5, s. 462-471
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Treatment strategies for abnormal mineral metabolism in chronic kidney disease are largely based on achieving target ranges of biomarkers that vary considerably over time, yet determinants of their variability are poorly defined. Methods: Observational study including 162 patients of three dialysis cohorts (peritoneal dialysis, n = 78; hemodialysis, n = 49; hemodiafiltration, n = 35). Clinical and biochemical determinants of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) variability were analyzed in the peritoneal dialysis cohort. All cohorts were used for comparison of PTH and FGF23 intra-subject variability (intra-class correlation), and their intra-subject variability in different modes of dialysis was explored. Results: High PTH variability was independently associated with lower 25-hydroxyvitamin D concentration and factors of lipid and glucose metabolism, whereas high FGF23 variability was mainly associated with lower baseline serum phosphorous. These results were consistent in multivariate and sensitivity analyses. The intra-subject variability of FGF23 was lower than for PTH irrespective of dialysis mode. Conclusions: Baseline vitamin D status and serum phosphorous are independent determinants of the longitudinal variation in PTH and FGF23, respectively. The clinical utility of FGF23 measurement remains unknown, yet it appears favorable based on its greater temporal stability than PTH in dialysis patients.
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| 10. |
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| 11. |
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| 12. |
- Kloster Smerud, Hilde, et al.
(författare)
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New treatment for IgA nephropathy : enteric budesonide targeted to the ileocecal region ameliorates proteinuria
- 2011
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP): Policy B. - 0931-0509 .- 1460-2385. ; 26:10, s. 3237-3241
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Tidskriftsartikel (refereegranskat)abstract
- Background. Systemic corticosteroid treatment has been shown to exert some protection against renal deterioration in IgA nephropathy (IgAN) but is not commonly recommended for long-term use due to the well-known systemic side effects. In this study, we investigated the efficacy and safety of a new enteric formulation of the locally acting glucocorticoid budesonide (Nefecon (R)), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria. less thanbrgreater than less thanbrgreater thanMethods. Budesonide 8 mg/day was given to 16 patients with IgAN for 6 months, followed by a 3-month follow-up period. The efficacy was measured as change in 24-h urine albumin excretion, serum creatinine and estimated glomerular filtration rate (eGFR). less thanbrgreater than less thanbrgreater thanResults. The median relative reduction in urinary albumin excretion was 23% during the treatment period (interquartile range: -0.36 to -0.04, P = 0.04) with pretreatment values ranging from 0.3 to 6 g/24 h (median: 1.5 g/24 h). The median reduction in urine albumin peaked at 40% (interquartile range: -0.58 to -0.15) 2 months after treatment discontinuation. Serum creatinine was reduced by 6% (interquartile range: -0.12 to -0.02; P = 0.003), and eGFR [Modification of Diet in Renal Disease (MDRD)] increased similar to 8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed. less thanbrgreater than less thanbrgreater thanConclusions. In the present pilot study, enteric budesonide targeted to the ileocecal region had a significant effect on urine albumin excretion, accompanied by a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation, while eGFR calculated from Cockcroft-Gault equation and cystatin C was not changed. Enteric budesonide may represent a new treatment of IgAN warranting further investigation.
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| 13. |
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| 14. |
- Rudholm Feldreich, Tobias, et al.
(författare)
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Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
- 2019
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Ingår i: JN. Journal of Nephrology (Milano. 1992). - Stockholm : Springer Science and Business Media LLC. - 1121-8428 .- 1724-6059. ; 32:1, s. 111-119
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Tidskriftsartikel (refereegranskat)abstract
- Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n=183, 55% women, mean age 63years, 46 cardiovascular deaths during follow-up (mean 43months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n=186, 73% women, mean age 62years, 45 cardiovascular deaths during follow-up (mean 12months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n=89, 37% women, mean age 46years).ResultsIn age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p=0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C=0.777 to C=0.799 and C=0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p=0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.ConclusionsOur proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Stenvinkel, Peter, et al.
(författare)
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Statin treatment and diabetes affect myeloperoxidase activity in maintenance hemodialysis patients
- 2006
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450 .- 1555-905X. ; 1:2, s. 281-287
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Tidskriftsartikel (refereegranskat)abstract
- Myeloperoxidase (MPO), which is secreted during activation of neutrophils, may serve as one mechanistic link among persistent inflammation, oxidative stress, and cardiovascular disease. This study related MPO activity to inflammatory and oxidative stress biomarkers, comorbidity, and ongoing medication in prevalent hemodialysis (HD) patients. In a cross-sectional evaluation of 115 prevalent (vintage 25 mo) HD patients (62 men; 63 +/- 1 yr), data on comorbidity (Davies score), diabetes, medication (statins and antiltypertensive drugs), nutritional status (subjective global assessment), blood lipids (cholesterol, HDL cholesterol, and triglycerides), inflammatory biomarkers (serum albumin, C-reactive protein, TNF-alpha, and IL-6), oxidative stress biomarkers (pentosidine, 8-hydroxydeoxyguanosine, and MPO activity) were recorded. Patients with MPO activity greater than the median had significantly (P < 0.05) lower serum albumin levels (33.2 +/- 0.7 versus 35.0 +/- 0.5 g/L), higher 8-hydroxydeoxyguanosine levels (1.26 +/- 0.08 versus 1.05 +/- 0.06 ng/mb, and a lower prevalence of statin treatment (18 versus 36%). Therefore, the median MPO activity was significantly (P < 0.05) lower (17.7 versus 26.6 Delta OD630/min per mg protein) in the subgroup of 31 HD patients with ongoing statin treatment. In a multiple regression model, correction for the impact of age, gender, vintage, serum cholesterol, serum albumin, comorbidity, diabetes, and statin use, only diabetes (P < 0.01) and statin use (P < 0.01) were significantly associated to MPO activity. Fourteen patients who had diabetes and were receiving statin treatment had markedly (P = 0.001) lower median (19.9 versus 41.2 Delta OD630/min per mg protein) MPO activity compared with 18 who had diabetes and were not taking statins. This cross-sectional study suggests that both diabetes and statin treatment affect MPO activity in prevalent HD patients.
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| 19. |
- Bárány-Wallje, Elsa, et al.
(författare)
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A critical reassessment of penetratin translocation across lipid membranes.
- 2005
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Ingår i: Biophys J. - 0006-3495. ; 89:4, s. 2513-21
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Tidskriftsartikel (refereegranskat)abstract
- Penetratin is a short, basic cell-penetrating peptide able to induce cellular uptake of a vast variety of large, hydrophiliccargos. We have reassessed the highly controversial issue of direct permeation of the strongly cationic peptide across negatively charged lipid membranes. Confocal laser scanning microscopy on rhodamine-labeled giant vesicles incubated with carboxyfluorescein-labeled penetratin yielded no evidence of transbilayer movement, in contradiction to previously reported results. Confocal fluorescence spectroscopy on black lipid membranes confirmed this finding, which was also not affected by application of a transmembrane electric potential difference.A novel dialysis assay based on tryptophan absorbance and fluorescence spectroscopy demonstrated that the permeability of small and large unilamellar vesicles to penetratin is,<10^-13m/s.Taken together, the results show that penetratin is not capable of overcoming model membrane systems irrespective of the bilayer curvature or the presence of a transmembrane voltage. Thus, direct translocation across the hydrophobic core of the plasmamembrane cannot account for the efficient uptake of penetratin into live cells, which is in accord with recent in vitro studies underlining the importance of endocytosis in the internalization process of cationic cell-penetrating peptides.
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| 20. |
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| 21. |
- Beshara, Soheir, et al.
(författare)
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Varying intervals of subcutaneous epoetin alfa in hemodialysis patients
- 2004
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Ingår i: JN. Journal of Nephrology (Milano. 1992). - 1121-8428 .- 1724-6059. ; 17:4, s. 525-530
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: The optimal subcutaneous (SC) epoetin alfa strategy is unestablished. The individual variability in dose requirements needs consideration. In this study, prolonged intervals were assessed in relation to varying dose requirements. METHODS: The study included 153 hemodialysis (HD) patients on stable SC epoetin alfa. Based on dose requirements, the patients received either 4,000 U (group I, n=51) or 10,000 U (group II, n=102) as whole 1 mL vials at prolonged intervals. The study comprised three 8-week periods: an initial period maintaining the basal regimens, an adjustment period where the intervals were prolonged, and a maintenance period. Alterations in hemoglobin (Hb), weekly doses and intervals in each group were compared. RESULTS: One hundred and thirty-seven patients completed the study (48 in group I and 89 in group II). In group I, the mean interval was prolonged from 5.4 +/- 1.9 to 7.8 +/- 3.1 days (p=0,01) with stable Hb and EPO doses. In group II, prolonged intervals were associated with a reduction in mean Hb below target level and a significant increase in EPO doses (p=0,002). Iron deficiency and inflammation could explain the poor response in approximately one-third of the patients. CONCLUSIONS: In HD patients, the optimal injection frequency should be individually adjusted. Prolonged intervals can be applied to patients with low-dose requirements. Observing iron status and inflammation is necessary for optimal response.
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| 22. |
- Bosi, Alessandro, et al.
(författare)
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Use of nephrotoxic medications in adults with chronic kidney disease in Swedish and US routine care
- 2022
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 15:3, s. 442-451
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Tidskriftsartikel (refereegranskat)abstract
- Background: To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3-5 in routine care.Methods: We studied cohorts of adults with confirmed CKD G3-5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (N = 57 880) and Geisinger, PA, USA (N = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression.Results: During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80-0.90] in SCREAM and OR 0.80 [95% CI 0.72-0.89] in Geisinger}.Conclusions: One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury.
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| 23. |
- Carlström, Mattias, et al.
(författare)
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Peritoneal dialysis impairs nitric oxide homeostasis and may predispose infants with low systolic blood pressure to cerebral ischemia
- 2016
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Ingår i: Nitric Oxide - Biology and Chemistry. - : Elsevier BV. - 1089-8603 .- 1089-8611. ; 58, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background & purpose Infants on chronic peritoneal dialysis (PD) have an increased risk of developing neurological morbidities; however, the underlying biological mechanisms are poorly understood. In this clinical study, we investigated whether PD-mediated impairment of nitric oxide (NO) bioavailability and signaling, in patients with persistently low systolic blood pressure (SBP), can explain the occurrence of cerebral ischemia. Methods & results Repeated blood pressure measurements, serial neuroimaging studies, and investigations of systemic nitrate and nitrite levels, as well as NO signaling, were performed in ten pediatric patients on PD. We consistently observed the loss of both inorganic nitrate (-17 ± 3%, P < 0.05) and nitrite (-34 ± 4%, P < 0.05) during PD, which may result in impairment of the nitrate-nitrite-NO pathway. Indeed, PD was associated with significant reduction of cyclic guanosine monophosphate levels (-59.4 ± 15%, P < 0.05). This reduction in NO signaling was partly prevented by using a commercially available PD solution supplemented with l-arginine. Although PD compromised nitrate-nitrite-NO signaling in all cases, only infants with persistently low SBP developed ischemic cerebral complications. Conclusions Our data suggests that PD impairs NO homeostasis and predisposes infants with persistently low SBP to cerebral ischemia. These findings improve current understanding of the pathogenesis of infantile cerebral ischemia induced by PD and may lead to the new treatment strategies to reduce neurological morbidities.
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| 24. |
- Carrero, Juan Jesus, et al.
(författare)
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Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality
- 2017
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 91:1, s. 244-251
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Tidskriftsartikel (refereegranskat)abstract
- Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death.
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| 25. |
- Chesnaye, Nicholas C., et al.
(författare)
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Association of Longitudinal High-Sensitivity Troponin T With Mortality in Patients With Chronic Kidney Disease
- 2022
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 79:4, s. 327-336
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously been assessed. OBJECTIVES This study determined whether various parameterizations of longitudinal cTnT measurements were associated with patient survival in the older population with advanced CKD. METHODS The EQUAL (European QUALity) study is an observational prospective cohort study that includes subjects with stage 4-5 CKD aged $65 years and not on dialysis. The study includes 176 participants in Sweden, where longitudinal information of cTnT was collected. The study uses joint models for longitudinal and time-to-event data to assess the longitudinal association between cTnT and survival. RESULTS There were 927 cTnT measurements (median 6 per patient) collected over a median follow-up of 2.4 years. The overall 5-year survival was 57% (95% CI: 46%-69%). Longitudinally measured cTnT was associated with mortality risk, with every SD increase in cTnT, at any time point, associated with a 3.3-fold increase in mortality risk (HR: 3.3; 95% CI: 2.5-4.6). The slope of the cTnT trajectory was also associated with increased mortality risk (HR: 3.2; 95% CI: 2.06.0), as was the area under the cTnT trajectory (HR: 4.2; 95% CI: 2.6-7.2), which reflected the cumulative cTnT exposure. CONCLUSIONS Longitudinally measured cTnT is independently associated with mortality risk in older patients with stage 4 and 5 CKD, which suggests that monitoring patients with cTnT could be a valuable tool for the identification of subjects with a high mortality risk.
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| 26. |
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| 27. |
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| 28. |
- Dzialanski, Zbigniew, et al.
(författare)
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Lactase persistence versus lactose intolerance : Is there an intermediate phenotype?
- 2016
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Ingår i: Clinical Biochemistry. - : Elsevier. - 0009-9120 .- 1873-2933. ; 49:3, s. 248-252
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Tidskriftsartikel (refereegranskat)abstract
- Background: According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist.Aim: To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test.Methods: A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274).Results: Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups.Conclusions: Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance.
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| 29. |
- Elinder, Carl-Gustaf, et al.
(författare)
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Variations in graft and patient survival after kidney transplantation in Sweden: caveats in interpretation of center effects when benchmarking.
- 2009
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 22:11, s. 1051-7
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Tidskriftsartikel (refereegranskat)abstract
- Benchmarking and comparisons between transplantation centers are becoming more common. A crude comparison indicated a 50% difference in patient survival between centers in Sweden. A 'task group' was formed to refute or confirm and learn from this observation. Patient survival and graft survival of 5 933 patients transplanted at three different transplantation centers in Sweden (Stockholm, Göteborg, and Malmö) were followed up until February 2007. Patient survival and graft survival were compared between the centers with and without consideration being given to important covariates such as time period, type of donation (living or deceased donor), gender, and age. A refined cohort of 2,956 adult patients that had been transplanted for the first time between 1991 and 2007 was assessed in more detail using Cox regression analysis. The difference in patient and transplant outcome observed in the crude comparison diminished considerably after adjustment for differences in case mix and time period of transplantation, and was neither evident nor significant after 1999. Patient survival and graft survival have improved considerably during the time period since 1991. The adjusted hazards ratio for mortality was 0.39 (95% CI 0.29-0.53) for patients who were transplanted after 1999 when compared with those transplanted between 1991 and 1994. Crude comparisons between results from transplantation centers may be severely confounded not only by case mix but also by differences in the proportion of patients transplanted during different time periods. Patient outcome and graft outcome have improved considerably since 1991, and after 1999 center effects were no longer apparent in Sweden.
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| 30. |
- Furuland, Hans, 1956-
(författare)
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Effects of Hemoglobin Normalization with Epoetin in Chronic Kidney Disease
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anemia is common in patients with chronic kidney disease (CDK), contributes to reduced Quality of Life (QoL) and is associated with cardiovascular disease, morbidity and mortality. Epoetin raises hemoglobin (Hb) and increases QoL and physical exercise capacity. Because of concerns about safety and economics, current anemia treatment with epoetin aims to achieve subnormal Hb (110-120 g/l). Normalization of Hb may be of additional benefit regarding QoL and cardiovascular effects. The present study examines the effects of Hb normalization with epoetin on safety variables, QoL, graft function after kidney transplantation, dialysis adequacy, hemorheology, hemodynamics and cardiac autonomic function in CKD patients. In a randomized, multicenter study comprising 416 pre-dialysis and dialysis patients no difference was observed between patients treated to a normal or a subnormal Hb level on mortality, thrombovascular events, serious adverse events, vascular access thrombosis and residual renal function. QoL was enhanced in a subgroup of hemodialysis patients. Pretransplant epoetin treatment directed toward normal Hb levels did not result in worse graft function during 6 postoperative months. Dialysis adequacy was reduced in a subgroup of hemodialysis patients after normalization of Hb. The blood flow properties of pre-dialysis patients were altered. The hemorheological investigation demonstrated that Hb normalization caused a parallel increase in hematocrit and blood viscosity without other hemorheological changes. While the total peripheral resistance index increased, the cardiac index (CI) decreased. In a separate study cardiac autonomic function, measured by heart rate variability, was decreased in pre-dialysis patients. It was improved, but not fully normalized, by Hb normalization. On the basis of this study, Hb normalization with epoetin appears to be safe and increases QoL in hemodialysis patients though may result in lower dialysis adequacy and increased blood pressure. A reduction in CI and improved cardiac autonomic function indicate a positive effect on cardiovascular function.
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| 31. |
- Gasparini, Alessandro, et al.
(författare)
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Prevalence and recognition of chronic kidney disease in Stockholm healthcare
- 2016
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 31:12, s. 2086-2094
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Tidskriftsartikel (refereegranskat)abstract
- Background. Chronic kidney disease (CKD) is common, but the frequency of albuminuria testing and referral to nephrology care has been difficult to measure. We here characterize CKD prevalence and recognition in a complete healthcare utilization cohort of the Stockholm region, in Sweden. Methods. We included all adult individuals (n = 1 128 058) with at least one outpatient measurement of IDMS-calibrated serum creatinine during 2006-11. Estimated glomerular filtration rate (eGFR) was calculated via the CKD-EPI equation and CKD was solely defined as eGFR <60 mL/min/1.73 m(2). We also assessed the performance of diagnostic testing (albuminuria), nephrology consultations, and utilization of ICD-10 diagnoses. Results. A total of 68 894 individuals had CKD, with a crude CKD prevalence of 6.11% [95% confidence interval (CI): 6.07-6.16%] and a prevalence standardized to the European population of 5.38% (5.33-5.42%). CKD was more prevalent among the elderly (28% prevalence >75 years old), women (6.85 versus 5.24% in men), and individuals with diabetes (17%), hypertension (17%) or cardiovascular disease (31%). The frequency of albuminuria monitoring was low, with 38% of diabetics and 27% of CKD individuals undergoing albuminuria testing over 2 years. Twenty-three per cent of the 16 383 individuals satisfying selected KDIGO criteria for nephrology referral visited a nephrologist. Twelve per cent of CKD patients carried an ICD-10 diagnostic code of CKD. Conclusions. An estimated 6% of the adult Stockholm population accessing healthcare has CKD, but the frequency of albuminuria testing, nephrology consultations and registration of CKD diagnoses was suboptimal despite universal care. Improving provider awareness and treatment of CKD could have a significant public health impact.
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| 32. |
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| 33. |
- Grigore, Teodora V. V., et al.
(författare)
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Fibroblast growth factor 23 is independently associated with renal magnesium handling in patients with chronic kidney disease
- 2023
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Ingår i: Frontiers in Endocrinology. - : FRONTIERS MEDIA SA. - 1664-2392. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDisturbances in magnesium homeostasis are common in patients with chronic kidney disease (CKD) and are associated with increased mortality. The kidney is a key organ in maintaining normal serum magnesium concentrations. To this end, fractional excretion of magnesium (FEMg) increases as renal function declines. Despite recent progress, the hormonal regulation of renal magnesium handling is incompletely understood. Fibroblast Growth Factor 23 (FGF23) is a phosphaturic hormone that has been linked to renal magnesium handling. However, it has not yet been reported whether FGF23 is associated with renal magnesium handling in CKD patients. MethodsThe associations between plasma FGF23 levels, plasma and urine magnesium concentrations and FEMg was investigated in a cross-sectional cohort of 198 non-dialysis CKD patients undergoing renal biopsy. ResultsFGF23 was significantly correlated with FEMg (Pearsons correlation coefficient = 0.37, p<0.001) and urinary magnesium (-0.14, p=0.04), but not with plasma magnesium. The association between FGF23 and FEMg remained significant after adjusting for potential confounders, including estimated glomerular filtration rate (eGFR), parathyroid hormone and 25-hydroxyvitamin D. ConclusionsWe report that plasma FGF23 is independently associated with measures of renal magnesium handling in a cohort of non-dialysis CKD patients. A potential causal relationship should be investigated in future studies.
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| 34. |
- Hayashi, Shirley Yumi, et al.
(författare)
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Left ventricular function in patients with chronic kidney disease evaluated by colour tissue Doppler velocity imaging
- 2006
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 21:1, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- Background. Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD) patients. Tissue Doppler velocity imaging (TVI) is a new objective method that accurately quantifies myocardial tissue velocities, deformation, time intervals and left ventricular (LV) filling pressure. In this study, TVI was compared with conventional echocardiography for the assessment of left ventricular (LV) function in pre-dialysis patients with different stages of CKD. The results obtained by TVI were used to analyse possible relationships between LV function and clinical factors such as hyperparathyroidism and hypertension that could influence LV function. Methods. Conventional echocardiography and TVI images were recorded in 40 patients (36 men and 4 women, mean age 60 +/- 14 years, range 28-80 years) and in 27 healthy controls (21 men and 6 women, mean age 58 +/- 17 years, range 28-82 years). Twenty-two patients had mild/moderate CKD (CCr > 29 ml/min; Group 1) and 18 patients had severe CKD (CCr <= 29 ml/min; Group 2). Using TVI, the myocardial tissue velocities (v; cm/s) for isovolumetric contraction (IVCv), peak systole (PSv), early (E') and late (A') diastolic filling velocities as well as strain rate (SR), mitral annulus displacement, isovolumetric relaxation time (IVRT) and LV filling pressure were estimated using TVI. The average of six LV wall measurements was used to evaluate LV global function. Results. Using TVI, we were able to identify significantly more patients with diastolic dysfunction than using conventional echocardiography (33 vs 26, P < 0.05). There was no difference in the prevalence of diastolic dysfunction between Group 1 and 2. However, using TVI, Group 2 CKD patients had lower E' velocities (6.2 +/- 1.9 vs 8.0 +/- 2.9 cm/s, P < 0.05) and higher IVRT (137.4 +/- 13 vs 88.2 +/- 26 ms, P < 0.001) in comparison with controls, indicating more accentuated diastolic dysfunction. Systolic blood pressure (SBP) was associated with E' velocities (rho = -0.68, P < 0.005) and E'/A' was strongly associated with SBP (rho = -0.60; P < 0.01) and PTH (rho = -0.64, P < 0.005) in Group 2. Using conventional echocardiography, there was no difference in the prevalence of systolic and diastolic dysfunction between patients with and without LVH. However, using TVI, patients with LVH had significantly lower IVCv (2.8 +/- 1.3 vs 3.8 +/- 1.5 and 3.8 +/- 1.5 cm/s, P < 0.05) and PSv (5.5 +/- 1.0 vs 6.3 +/- 1.2 and 6.4 +/- 1.3 cm/s, P < 0.05) compared with patients without LVH and controls, and they also had lower E' velocities (7.1 +/- 2.7 vs 8.0 +/- 2.9 cm/s, P < 0.05) compared with controls, indicating disturbances in systolic and diastolic left ventricular function. Conclusions. TVI provided additional information on left ventricular function in CKD patients. In patients with advanced renal failure, TVI revealed more accentuated diastolic dysfunction associated with increased systolic blood pressure (SBP) and increased levels of PTH. TVI also demonstrated disturbances in contractility and contraction in patients with LVH, which could not be detected by conventional echocardiography.
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| 35. |
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| 36. |
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| 37. |
- Mok, Yejin, et al.
(författare)
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Albuminuria as a predictor of cardiovascular outcomes in patients with acute myocardial infarction
- 2019
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Ingår i: Journal of the American Heart Association. - 2047-9980 .- 2047-9980. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Background. In patients with myocardial infarction ( MI ), reduced kidney function is recognized as an important predictor of poor prognosis, but the impact of albuminuria, a representative measure of kidney damage, has not been extensively evaluated.Methods and Results. In the SCREAM (Stockholm Creatinine Measurements) project (2006-2012), we identified 2469 patients with incident MI with dipstick proteinuria measured within a year before MI (427 patients also had urine albumin to creatinine ratio [ ACR ] measured concurrently) and obtained estimates for ACR with multiple imputation in participants with data solely on dipstick proteinuria. We quantified the association of ACR with the post- MI composite and individual outcomes of all-cause mortality, cardiovascular mortality, recurrent MI , ischemic stroke, or heart failure using Cox models and then evaluated the improvement in C statistic. During a median follow-up of 1.0 year after MI , 1607 participants (65.1%) developed the post- MI composite outcome. Higher ACR levels were independently associated with all outcomes except for ischemic stroke. Per 8-fold higher ACR (eg, 40 versus 5 mg/g), the hazard ratio of composite outcome was 1.21 (95% CI , 1.08-1.35). The addition of the ACR improved the C statistic of the post- MI composite by 0.040 (95% CI, 0.030-0.051). Largely similar results were obtained regardless of diabetic status and when ACR or dipstick was separately analyzed without imputation.Conclusions. In patients with MI , albuminuria was a potent predictor of subsequent outcomes, suggesting the importance of paying attention to the information on albuminuria, in addition to kidney function, in this high-risk population.
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| 38. |
- Pistis, Kristin Danielson, et al.
(författare)
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The effect of high-dose vitamin D supplementation on hepcidin-25 and erythropoiesis in patients with chronic kidney disease
- 2023
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Ingår i: BMC Nephrology. - : BioMed Central (BMC). - 1471-2369 .- 1471-2369. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hepcidin is considered to play a central role in the pathophysiology of renal anemia. Recent studies in healthy individuals have demonstrated a suppressive effect of vitamin D (VD) on the expression of hepcidin. In this post-hoc analysis based on a randomized controlled study, we evaluated the effect of supplementing chronic kidney disease (CKD) patients (stage G3-G4) with a high daily dose of native VD on serum levels of hepcidin-25, the hepcidin/ferritin ratio, as well as on markers of erythropoiesis.Methods: Patients with CKD stage G3-G4 included in a double blind, randomized, placebo (PBO) controlled study with available hepcidin measurements were analyzed. Study subjects received either 8000 international units (IU) of cholecalciferol daily or PBO for 12 weeks. We evaluated the change in markers of hepcidin expression, erythropoiesis, and iron status from baseline to week 12 and compared the change between the groups.Results: Eighty five patients completed the study. Calcitriol, but not 25-hydroxyvitamin D (25(OH) D), was inversely correlated with serum levels of hepcidin-25 (rho = -0,38; p = < 0, 01 and rho = -0,02; p = 0, 89, respectively) at baseline. Supplementation with VD significantly raised the serum concentration of serum 25(OH)D in the treatment group (from 54 (39-71) to 156 (120-190) nmol/L; p = < 0, 01)) but had no effect on any of the markers of hepcidin, erythropoiesis, or iron status in the entire cohort. However, we did observe an increase in hemoglobin (HB) levels and transferrin saturation (TSAT) as compared to the PBO group in a subgroup of patients with low baseline 25(OH)D levels (< 56 nmol/L). In contrast, in patients with high baseline 25(OH)D values (>= 56 nmol/L), VD supplementation associated with a decrease in HB levels and TSAT (p = 0,056) within the VD group in addition to a decrease in hepcidin levels as compared to the PBO group.Conclusion: High-dose VD supplementation had no discernible effect on markers of hepcidin or erythropoiesis in the entire study cohort. However, in patients with low baseline 25(OH)D levels, high-dose VD supplementation associated with beneficial effects on erythropoiesis and iron availability. In contrast, in patients with elevated baseline 25(OH)D levels, high-dose VD supplementation resulted in a decrease in hepcidin levels, most likely due to a deterioration in iron status.
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| 39. |
- Robertsson Grossmann, Katarina, et al.
(författare)
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Kidney outcomes in early adolescence following perinatal asphyxia and hypothermia-treated hypoxic-ischaemic encephalopathy
- 2023
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Ingår i: Pediatric Nephrology. - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X. ; 38:4, s. 1205-1214
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute kidney injury (AKI) remains common among infants with hypothermia-treated hypoxic-ischaemic encephalopathy (HIE). Little is known about long-term kidney outcomes following hypothermia treatment. We recently reported that 21% of survivors of hypothermia-treated HIE had decreased estimated glomerular filtration rate (eGFR) based on plasma creatinine in early adolescence. Here, we assessed kidney functions more comprehensively in our population-based cohort of children born in Stockholm 2007–2009 with a history of hypothermia-treated HIE. Methods: At 10–12 years of age, we measured cystatin C (cyst C) to estimate GFR. Children with decreased cyst C eGFR also underwent iohexol clearance examination. We measured urine-albumin/creatinine ratio, blood pressure (BP) and kidney volume on magnetic resonance imaging. Fibroblast growth factor 23 (FGF 23) levels in plasma were assessed by enzyme-linked immunosorbent assay (ELISA). Outcomes were compared between children with and without a history of neonatal AKI. Results: Forty-seven children participated in the assessment. Two children (2/42) had decreased cyst C eGFR, for one of whom iohexol clearance confirmed mildly decreased GFR. One child (1/43) had Kidney Disease Improving Global Outcomes (KDIGO) category A2 albuminuria, and three (3/45) had elevated office BP. Subsequent ambulatory 24-h BP measurement confirmed high normal BP in one case only. No child had hypertension. Kidney volume and FGF 23 levels were normal in all children. There was no difference in any of the parameters between children with and without a history of neonatal AKI. Conclusion: Renal sequelae were rare in early adolescence following hypothermia-treated HIE regardless of presence or absence of neonatal AKI. Graphical abstract: [Figure not available: see fulltext.].
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| 40. |
- Szeitz, Beáta, et al.
(författare)
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In-depth proteomic analysis reveals unique subtype-specific signatures in human small-cell lung cancer
- 2022
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 12:9, s. 1060-1060
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Small-cell lung cancer (SCLC) molecular subtypes have been primarily characterized based on the expression pattern of the following key transcription regulators: ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P) and YAP1 (SCLC-Y). Here, we investigated the proteomic landscape of these molecular subsets with the aim to identify novel subtype-specific proteins of diagnostic and therapeutic relevance.METHODS: Pellets and cell media of 26 human SCLC cell lines were subjected to label-free shotgun proteomics for large-scale protein identification and quantitation, followed by in-depth bioinformatic analyses. Proteomic data were correlated with the cell lines' phenotypic characteristics and with public transcriptomic data of SCLC cell lines and tissues.RESULTS: Our quantitative proteomic data highlighted that four molecular subtypes are clearly distinguishable at the protein level. The cell lines exhibited diverse neuroendocrine and epithelial-mesenchymal characteristics that varied by subtype. A total of 367 proteins were identified in the cell pellet and 34 in the culture media that showed significant up- or downregulation in one subtype, including known druggable proteins and potential blood-based markers. Pathway enrichment analysis and parallel investigation of transcriptomics from SCLC cell lines outlined unique signatures for each subtype, such as upregulated oxidative phosphorylation in SCLC-A, DNA replication in SCLC-N, neurotrophin signalling in SCLC-P and epithelial-mesenchymal transition in SCLC-Y. Importantly, we identified the YAP1-driven subtype as the most distinct SCLC subgroup. Using sparse partial least squares discriminant analysis, we identified proteins that clearly distinguish four SCLC subtypes based on their expression pattern, including potential diagnostic markers for SCLC-Y (e.g. GPX8, PKD2 and UFO).CONCLUSIONS: We report for the first time, the protein expression differences among SCLC subtypes. By shedding light on potential subtype-specific therapeutic vulnerabilities and diagnostic biomarkers, our results may contribute to a better understanding of SCLC biology and the development of novel therapies.
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| 41. |
- Szummer, Karolina, et al.
(författare)
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Time in therapeutic range and outcomes after warfarin initiation in newly diagnosed atrial fibrillation patients with renal dysfunction
- 2017
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Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980 .- 2047-9980. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unknown whether renal dysfunction conveys poor anticoagulation control in warfarin-treated patients with atrial fibrillation and whether poor anticoagulation control associates with the risk of adverse outcomes in these patients.METHODS AND RESULTS: This was an observational study from the Stockholm CREatinine Measurements (SCREAM) cohort including all newly diagnosed atrial fibrillation patients initiating treatment with warfarin (n=7738) in Stockholm, Sweden, between 2006 and 2011. Estimated glomerular filtration rate (eGFR; mL/min per 1.73 m(2)) was calculated from serum creatinine. Time-in-therapeutic range (TTR) was assessed from international normalized ratio (INR) measurements up to warfarin cessation, adverse event, or end of follow-up (2 years). Adverse events considered a composite of intracranial hemorrhage, ischemic stroke, myocardial infarction, or death. During median 254 days, TTR was 83%, based on median 21 INR measurements per patient. TTR was 70% among patients with eGFR <30, around 10% lower than in those with normal renal function. During observation, adverse events occurred in 4.0% of patients, and those with TTR ≤75% were at higher adverse event risk. This was independent of patient characteristics, comorbidities, number of INR tests, days exposed to warfarin, and, notably, independent of eGFR: adjusted odds ratio (OR) 1.84 (95% CI, 1.41-2.40) for TTR 75% to 60% and adjusted OR 2.09 (1.59-2.74) for TTR <60%. No interaction was observed between eGFR and TTR in association to adverse events (P=0.2).CONCLUSION: Severe chronic kidney disease (eGFR <30) patients with atrial fibrillation have worse INR control while on warfarin. An optimal TTR (>75%) is associated with lower risk of adverse events, independently of underlying renal function.
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| 42. |
- Wikström, Björn, et al.
(författare)
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Iron isomaltoside 1000 : a new intravenous iron for treating iron deficiency in chronic kidney disease
- 2011
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Ingår i: JN. Journal of Nephrology (Milano. 1992). - 1121-8428 .- 1724-6059. ; 24:5, s. 589-596
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with chronic kidney disease (CKD) often suffer from iron deficiency anemia necessitating treatment with intravenous iron. This study was designed to assess the safety of iron isomaltoside 1000 (Monofer) in CKD patients. The secondary objective was to assess its effect on iron deficiency anemia. Methods: This open-label, noncomparative, multi-center trial assigned 182 patients with CKD (n=161 in dialysis and n=21 in predialysis) to iron isomaltoside 1000 either as 4 intravenous bolus injections of 100-200 mg iron per dose or as a fast high-dose infusion at baseline. Patients were generally undergoing erythropoiesis-stimulating agent (ESA) treatment (82%), and the dosage was to be kept constant during the trial. They were either switched from an existing parenteral maintenance therapy (n=144) or were not currently being treated with parenteral iron (n=38). Frequency of adverse events (AEs) and changes in markers of iron deficiency anemia were measured during 8 weeks from baseline. Results: Nineteen treatment-related AEs occurred in 13 patients (7.1%) and after 584 treatments (3.3%). No anaphylactic or delayed allergic reactions were observed. There were no clinically significant changes in routine clinical laboratory tests or vital signs. Hemoglobin increased from 99.2 g/L (SD=9.0) at baseline to 111.2 g/L (SD=14.7) at week 8 in patients not currently treated with parenteral iron (p<0.001) and increased slightly or stabilized in patients in maintenance therapy. S-Ferritin, s-iron and transferrin saturation increased significantly at all visits. Conclusions: Iron isomaltoside 1000 was clinically well tolerated, safe and effective. This new intravenous iron may offer a further valuable choice in treating the anemia of CKD.
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| 43. |
- Xu, Hong, et al.
(författare)
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eGFR and the risk of community-acquired infections
- 2017
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Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 12:9, s. 1399-1408
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Community-acquired infections are common, contributing to adverse outcomes and increased health care costs. We hypothesized that, with lower eGFR, the incidence of community-acquired infections increases, whereas the pattern of site-specific infections varies.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 1,139,470 health care users (mean age =52±18 years old, 53% women) from the Stockholm CREAtinine Measurements Project, we quantified the associations of eGFR with the risk of infections, overall and major types, over 12 months.RESULTS: A total of 106,807 counts of infections were recorded throughout 1,128,313 person-years. The incidence rate of all infections increased with lower eGFR from 74/1000 person-years for individuals with eGFR=90-104 ml/min per 1.73 m(2) to 419/1000 person-years for individuals with eGFR<30 ml/min per 1.73 m(2). Compared with eGFR of 90-104 ml/min per 1.73 m(2), the adjusted incidence rate ratios of community-acquired infections were 1.08 (95% confidence interval, 1.01 to 1.14) for eGFR of 30-59 ml/min per 1.73 m(2) and 1.53 (95% confidence interval, 1.39 to 1.69) for eGFR<30 ml/min per 1.73 m(2). The relative proportions of lower respiratory tract infection, urinary tract infection, and sepsis became increasingly higher along with lower eGFR strata (e.g., low respiratory tract infection accounting for 25% versus 15% of community-acquired infections in eGFR<30 versus 90-104 ml/min per 1.73 m(2), respectively). Differences in incidence associated with eGFR were in general consistent for most infection types, except for nervous system and upper respiratory tract infections, for which no association was observed.CONCLUSIONS: This region-representative health care study finds an excess community-acquired infections incidence in individuals with mild to severe CKD. Lower respiratory tract infection, urinary tract infection, and sepsis are major infections in CKD.
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| 44. |
- Xu, Hong, et al.
(författare)
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Estimated glomerular filtration rate and the risk of cancer
- 2019
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Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 14:4, s. 530-539
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Community-based reports regarding eGFR and the risk of cancer are conflicting. We here explore plausible links between kidney function and cancer incidence in a large Scandinavian population-based cohort.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the Stockholm Creatinine Measurements project, we quantified the associations of baseline eGFR with the incidence of cancer among 719,033 Swedes ages ≥40 years old with no prior history of cancer. Study outcomes were any type and site-specific cancer incidence rates on the basis of International Classification of Diseases-10 codes over a median follow-up of 5 years. To explore the possibility of detection bias and reverse causation, we divided the follow-up time into different time periods (≤12 and >12 months) and estimated risks for each of these intervals.RESULTS: In total, 64,319 cases of cancer (affecting 9% of participants) were detected throughout 3,338,226 person-years. The relationship between eGFR and cancer incidence was U shaped. Compared with eGFR of 90-104 ml/min, lower eGFR strata associated with higher cancer risk (adjusted hazard ratio, 1.08; 95% confidence interval, 1.05 to 1.11 for eGFR=30-59 ml/min and adjusted hazard ratio, 1.24; 95% confidence interval, 1.15 to 1.35 for eGFR<30 ml/min). Lower eGFR strata were significantly associated with higher risk of skin, urogenital, prostate, and hematologic cancers. Any cancer risk as well as skin (nonmelanoma) and urogenital cancer risks were significantly elevated throughout follow-up time, but they were higher in the first 12 months postregistration. Associations with hematologic and prostate cancers abrogated after the first 12 months of observation, suggesting the presence of detection bias and/or reverse causation.CONCLUSIONS: There is a modestly higher cancer risk in individuals with mild to severe CKD driven primarily by skin and urogenital cancers, and this is only partially explained by bias.
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