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- 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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- Dai, Lu, et al.
(författare)
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Early vascular ageing and cellular senescence in chronic kidney disease
- 2019
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Ingår i: Computational and Structural Biotechnology Journal. - Stockholm : Karolinska Institutet, Dept of Clinical Science, Intervention and Technology. - 2001-0370.
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by progressive vascular dis- ease, systemic inflammation, muscle wasting and frailty. The predominant early vascular ageing (EVA) process mediated by medial vascular calcification (VC) results in a marked discrepancy between chronological and bio- logical vascular age in CKD. Though the exact underlying mechanisms of VC and EVA are not fully elucidated, ac- cumulating evidence indicates that cellular senescence - and subsequent chronic inflammation through the senescence-associated secretary phenotype (SASP) - plays a fundamental role in its initiation and progression. In this review, we discuss the pathophysiological links between senescence and the EVA process in CKD, with focus on cellular senescence and media VC, and potential anti-ageing therapeutic strategies of senolytic drugs targeting cellular senescence and EVA in CKD.
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- Davies, Simon J., et al.
(författare)
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Longitudinal relationships between fluid status, inflammation, urine volume and plasma metabolites of icodextrin in patients randomized to glucose or icodextrin for the long exchange
- 2008
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Ingår i: NEPHROLOGY DIALYSIS TRANSPLANTATION. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 23:9, s. 2982-2988
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Konferensbidrag (refereegranskat)abstract
- Background. Randomized trials have shown that icodextrin reduces the volume of extra-cellular fluid (ECFv) with variable effects on residual renal function. To explore this fluid shift and its possible mechanisms in more detail, prospectively collected data from one such trial, including measures of inflammation (C-reactive protein, tumor necrosis factor-a, albumin and low and high molecular weight hyaluronan) ANP (atrial naturetic peptide), an indirect marker of intra-vascular Volume, plasma concentrations of icodextrin metabolites and alpha-amylase activity were analysed. Methods. 50 patients were randomized to either 2,27% glucose or icodextrin (n = 28) ford long exchange following a month run in. Blood samples were obtained at - 1, 0, 3 and 6 months, coincident with measurements Of urine volume and fluid status. Results. In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine Volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = -0.46, P = 0.007. in patients randomized to icodextrin, but not glucose. There were no relationships between fluid Status and any inflammatory markers at any point of the Study, with the exception of albumin at baseline, r = -0.39, P = 0.007. Amylase activities at -1 month and baseline were highly correlated, r = 0.89, P < 0.0001. Within patients, concentrations of icodextrin metabolites were highly correlated: the only predictor of between-patient variability oil multivariate analysis was body weight. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily Ultrafiltration, urine volume, fluid or inflammatory status. Conclusions. This analysis supports observational data that changes in fluid status are associated with changes ill urine volume. Icodextrin was not associated with a greater fall ill urine Output despite its larger effect on ECFv Changes ill fluid status Could not be explained or did not appeal to influence systemic inflammation. Nor call they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution.
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- 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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- González-Ortiz, Ailema, et al.
(författare)
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Plant-based diets, insulin sensitivity and inflammation in elderly men with chronic kidney disease.
- 2020
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Ingår i: JN. Journal of Nephrology (Milano. 1992). - : Springer Science and Business Media LLC. - 1121-8428 .- 1724-6059. ; 33, s. 1091-1101
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In persons with CKD, adherence to plant-based diets is associated with lower risk of CKD progression and death, but underlying mechanisms are poorly characterized. We here explore associations between adherence to plant-based diets and measures of insulin sensitivity and inflammation in men with CKD stages 3-5.METHODS: Cross-sectional study including 418 men free from diabetes, aged 70-71 years and with cystatin-C estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and not receiving kidney-specific dietetic advice. Information from 7-day food records was used to evaluate the adherence to a plant-based diet index (PBDi), which scores positively the intake of plant-foods and negatively animal-foods. Insulin sensitivity and glucose disposal rate were assessed with the gold-standard hyperinsulinemic euglycemic glucose clamp technique. Inflammation was evaluated by serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6. Associations were explored through linear regression and restricted cubic splines.RESULTS: The majority of men had CKD stage 3a. Hypertension and cardiovascular disease were the most common comorbidities. The median PBDi was 38 (range 14-55). Across higher quintiles of PBDi (i.e. higher adherence), participants were less often smokers, consumed less alcohol, had lower BMI and higher eGFR (P for trend <0.05 for all). Across higher PBDi quintiles, patients exhibited higher insulin sensitivity and lower inflammation (P for trend <0.05). After adjustment for eGFR, lifestyle factors, BMI, comorbidities and energy intake, a higher PBDi score remained associated with higher glucose disposal rate and insulin sensitivity as well as with lower levels of IL-6 and CRP.CONCLUSION: In elderly men with non-dialysis CKD stages 3-5, adherence to a plant-based diet was associated with higher insulin sensitivity and lower inflammation, supporting a possible role of plant-based diets in the prevention of metabolic complications of CKD.
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| 9. |
- Haarhaus, Mathias, 1967-
(författare)
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Bone alkaline phosphatase isoforms in chronic kidney disease : mineral and bone disorder
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic kidney disease (CKD) is associated with increased mortality and cardiovascular complications. Disturbances in mineral metabolism occur early In study I we identified the novel BALP isoform Blx in 20% of patients with mild to moderate CKD. Blx was associated with lower glomerular filtration rate and higher serum phosphate and calcium x phosphate product, which are risk factors for cardiovascular mortality in CKD. We also identified the BALP isoforms B/I, Bl and B2 as predictors of total hip bone mineral density.Study II was an experimental study, investigating the role of the BALP isoforms in phosphate induced calcification of human aortic smooth muscle cells (HASMCs). We found that the ALP expressed in HASMCs is exclusively BALP. Phosphate induced calcification of HASMCs was associated with increased BALP isoforms B/I, Blx, and B2 activities, which implies functional differences between the BALP isoforms in HASMC calcification.In study III we investigated the association of BALP isoforms in serum and histomorphometric parameters of bone in patients on chronic hemodialysis. W e identified the BALP isoform Blx as a novel marker for reduced osteoblastic activity.Study IV was a prospective cohort study of the association of serum BALP isoforms with aortic calcification and vascular stiffness in prevalent chronic dialysis patients. Blx was associated with baseline and time varying vascular stiffness, determined by pulse wave velocity, but not with calcification of the abdominal aorta. We also found an association of Blx with better event-free survival.In conclusion, these studies demonstrate that the BALP isoforms, especially isoform Blx, are involved in different aspects of CKD-MBD. This opens up for further research to identify the BALP isoforms as diagnostic markers and possible treatment targets in CKD-MBD.
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