1,721,013 research outputs found
Added value of serum-cystatin C in cardiac surgery patients with cpb developing AKI
No full textAims. AKI is common after cardiac surgery involving CPB. S-cystatin C is a novel early biomarker for AKI awaiting validation in this setting. Goal was to develop a clinical predictive model for AKI and test the added value of s-cystatin C within the first
24 hrs post-op.
Methods. 259 patients were enrolled. Patients with severe pre-existing renal insufficiency were excluded (eGFR<15 ml/min). Urine and blood samples were obtained immediately before initiation of CPB, at 3h, 6h, 12h and 24h post-op. Patients were retrospectively divided into 2 groups, AKI (n=84)(32%) and non-AKI (n=175)(68%), based on the AKIN criteria (increase in s-Creat ≥ 0.3 mg/dl or ≥ 50% compared to baseline within 48h or reduction in Urine output <0.5 ml/kg/h for more than 6h). Statistical
analysis to determine which clinical factors were predictive for AKI was performed (diabetes was not included). Subsequent analysis of the added value of serum-cystatin C to this model.
Results. Only duration of CPB, BMI and pre-op eGFR had predictive value in the clinical setting with the following combined AUC scores for AKI: 0.737 (3h post-op), 0.767 (6h post-op), 0.745 (12h post-op) and 0.755 (24h post-op). Addition of s-cystatin C increased the discriminative power at time points preop, 3h post-op, 6h post-op and 12h post-op (AUC scores of 0.776, 0.823 and 0.798 resp, all p<0.05 compared to clinical model alone).
Conclusion. Addition of s-cystatin C to a predictive clinical model for AKI has significant added value
Pre-ICU characteristics in cardiac surgery patients with CPB developing AKI
No full textAims. AKI is common after cardiac surgery involving CPB. Lack of reliable early detection methods for post-op AKI limits timely therapeutic intervention. A number of new biomarkers for AKI await validation in this setting. Analysis of a database was
performed to define baseline patient and biomarker characteristics in patients developing AKI.
Methods. 259 patients were enrolled. Patients with severe pre-existing renal insufficiency were excluded (eGFR<15ml/min). Urine and blood samples were obtained immediately before initiation of CPB. Patients were retrospectively divided into 2 groups,
AKI (n=84) and non-AKI (n=175), based on the AKIN criteria (increase in s-Creat ≥ 0.3 mg/dl or ≥ 50% compared to baseline within 48h or reduction in Urine output <0.5 ml/kg/h for more than 6h). Statistical analysis of all characteristics before arrival on the ICU was performed.
Results. AKI patients (32% of total) were older (70 yrs (SD= 9) vs 67 (11), p=0.043) with higher BMI’s (27.7 (4.8) vs. 26.7 (4.3), p=0.036). As to be expected baseline eGFR (CKD-EPI, in ml/min) was lower in the AKI-group (69.49 (20.30) vs. 76.45 (15.01), p=0.024). Both baseline urinary-NGAL (μg/l)(1211 (2172) vs. 749 (946), p=0.020) and serum-cystatin C (in mg/L)(0.98 (0.39) vs 0.86 (0.36), p=0.0175) were statistically higher in the AKI group and CPB time (in minutes) was significantly longer: 163 (63) vs 121 (51), p<0.0001.
Conclusion. u-NGAL and s-Cystatin most likely reflect pre-existing kidney dysfunction (like eGFR). CPB time is a significant factor for development of AKI, which is amenable to improvement
Pre-ICU characteristics in cardiac surgery patients with CPB developing AKI
No full textAims. AKI is common after cardiac surgery involving CPB. Lack of reliable early detection methods for post-op AKI limits timely therapeutic intervention. A number of new biomarkers for AKI await validation in this setting. Analysis of a database was
performed to define baseline patient and biomarker characteristics in patients developing AKI.
Methods. 259 patients were enrolled. Patients with severe pre-existing renal insufficiency were excluded (eGFR<15ml/min). Urine and blood samples were obtained immediately before initiation of CPB. Patients were retrospectively divided into 2 groups,
AKI (n=84) and non-AKI (n=175), based on the AKIN criteria (increase in s-Creat ≥ 0.3 mg/dl or ≥ 50% compared to baseline within 48h or reduction in Urine output <0.5 ml/kg/h for more than 6h). Statistical analysis of all characteristics before arrival on the ICU was performed.
Results. AKI patients (32% of total) were older (70 yrs (SD= 9) vs 67 (11), p=0.043) with higher BMI’s (27.7 (4.8) vs. 26.7 (4.3), p=0.036). As to be expected baseline eGFR (CKD-EPI, in ml/min) was lower in the AKI-group (69.49 (20.30) vs. 76.45 (15.01), p=0.024). Both baseline urinary-NGAL (μg/l)(1211 (2172) vs. 749 (946), p=0.020) and serum-cystatin C (in mg/L)(0.98 (0.39) vs 0.86 (0.36), p=0.0175) were statistically higher in the AKI group and CPB time (in minutes) was significantly longer: 163 (63) vs 121 (51), p<0.0001.
Conclusion. u-NGAL and s-Cystatin most likely reflect pre-existing kidney dysfunction (like eGFR). CPB time is a significant factor for development of AKI, which is amenable to improvement
Added value of serum-cystatin C in cardiac surgery patients with cpb developing AKI
No full textAims. AKI is common after cardiac surgery involving CPB. S-cystatin C is a novel early biomarker for AKI awaiting validation in this setting. Goal was to develop a clinical predictive model for AKI and test the added value of s-cystatin C within the first
24 hrs post-op.
Methods. 259 patients were enrolled. Patients with severe pre-existing renal insufficiency were excluded (eGFR<15 ml/min). Urine and blood samples were obtained immediately before initiation of CPB, at 3h, 6h, 12h and 24h post-op. Patients were retrospectively divided into 2 groups, AKI (n=84)(32%) and non-AKI (n=175)(68%), based on the AKIN criteria (increase in s-Creat ≥ 0.3 mg/dl or ≥ 50% compared to baseline within 48h or reduction in Urine output <0.5 ml/kg/h for more than 6h). Statistical
analysis to determine which clinical factors were predictive for AKI was performed (diabetes was not included). Subsequent analysis of the added value of serum-cystatin C to this model.
Results. Only duration of CPB, BMI and pre-op eGFR had predictive value in the clinical setting with the following combined AUC scores for AKI: 0.737 (3h post-op), 0.767 (6h post-op), 0.745 (12h post-op) and 0.755 (24h post-op). Addition of s-cystatin C increased the discriminative power at time points preop, 3h post-op, 6h post-op and 12h post-op (AUC scores of 0.776, 0.823 and 0.798 resp, all p<0.05 compared to clinical model alone).
Conclusion. Addition of s-cystatin C to a predictive clinical model for AKI has significant added value
Glutathione and mitochondria determine acute defense responses and adaptive processes in cadmium-induced oxidative stress and toxicity of the kidney
No full textCadmium (Cd2+) induces oxidative stress that ultimately defines cell fate and pathology. Mitochondria are the main energy-producing organelles in mammalian cells, but they also have a central role in formation of reactive oxygen species, cell injury, and death signaling. As the kidney is the major target in Cd2+ toxicity, the roles of oxidative signature and mitochondrial function and biogenesis in Cd2+-related stress outcomes were investigated in vitro in cultured rat kidney proximal tubule cells (PTCs) (WKPT-0293 Cl.2) for acute Cd2+ toxicity (1–30 µM, 24 h) and in vivo in Fischer 344 rats for sub-chronic Cd2+ toxicity (1 mg/kg CdCl2 subcutaneously, 13 days). Whereas 30 µM
Cd2+ caused ~50 % decrease in cell viability, apoptosis peaked at 10 µM Cd2+ in PTCs. A steep, dose-dependent decline in reduced glutathione (GSH) content occurred after acute exposure and an increase of the oxidized glutathione (GSSG)/GSH ratio. Quantitative PCR analyses evidenced increased antioxidative enzymes (Sod1, Gclc, Gclm), proapoptotic Bax, metallothioneins 1A/2A, and decreased antiapoptotic proteins (Bcl-xL, Bcl-w). The positive regulator of mitochondrial biogenesis Pparγ and mitochondrial DNA was increased, and cellular ATP was unaffected with Cd2+ (1–10 µM). In vivo, active caspase-3, and hence apoptosis, was detected by FLIVO injection in the kidney cortex of Cd2+-treated rats together with an increase in Bax mRNA.
However, antiapoptotic genes (Bcl-2, Bcl-xL, Bcl-w) were
also upregulated. Both GSSG and GSH increased with chronic Cd2+ exposure with no change in GSSG/GSH ratio and augmented expression of antioxidative enzymes (Gpx4, Prdx2). Mitochondrial DNA, mitofusin 2, and Pparα were increased indicating enhanced mitochondrial biogenesis and fusion. Hence, these results demonstrate a clear involvement of higher mitochondria copy numbers or mass and mitochondrial function in acute defense against oxidative stress induced by Cd2+ in renal PTCs as well as in adaptive processes associated with chronic renal Cd2+ toxicity.The authors would like to thank Rosette Beenaerts, Biomedical Research Institute, Hasselt University for her technical assistance and Dr. Michael D. Garrick at the Department of Biochemistry, SUNY, Buffalo, NY 14214, USA for the Fischer 344 rats. This work was supported by Hasselt University [BOF (Bijzonder onderzoeksfonds) projects; BOF08G01] through a PhD grant for Ambily Ravindran Nair and a grant from the Deutsche Forschungsgemeinschaft (DFG TH345/11-1) to Frank Thevenod. Additional funding came from tUL-impulsfinanciering (project toxicology), and Methusalem project (08M03VGRJ)
Characterization of a new rat model for the cardio-renal syndrome
No full textThe cardio-renal syndrome (CRS) is an umbrella term for life-threatening diseases in which cardiac and renal dysfunction occur simultaneously. It has been shown that heart failure patients with an increase in intra-abdominal pressure and central venous pressure (CVP), indicating the presence of abdominal and venous congestion, have a higher risk to develop CRS due to worsening renal function. It is hypothesized that abdominal venous congestion impairs heart and kidney function by causing damage to the heart and kidneys. Abdominal venous congestion was induced via constriction of the thoracic vena cava inferior (VCI). The effect of this constriction on heart, kidney and liver function was followed-up for twelve weeks after surgery via different in vivo and in vitro experiments.
It was shown that VCI constriction increased abdominal CVP, but that this increase had a limited effect on heart and kidney function. On the other hand, liver function deteriorated after VCI constriction. Therefore, it can be concluded that the rat model is validated as abdominal venous congestion was induced via constriction of the VCI. As the effect of VCI constriction on heart and kidney function was limited, the presence of abdominal venous congestion was insufficient to induce CRS. Consequently, in future CRS research, the role of abdominal venous congestion in CRS development and progression can be further explored by combining this rat model with other models of heart or kidney failure
Development and characterization of a clinically relevant rat model of diabetic cardiomyopathy
No full textDiabetic cardiomyopathy (DCM) is a devastating disease of the heart, which increases the risk of heart failure in individuals with diabetes mellitus (DM). DCM is characterized by structural and functional changes of the myocardium, which are attributable only to the presence of DM and not to confounding factors or diseases. To date, little is known about the pathophysiology of this disease and there is no specific treatment available. Therefore, a clinically relevant animal model, in which DCM is developed after induction of DM, is warranted.
This study showed that the combination of a high fat diet and a low dose of streptozotocin is efficient to induce type 2 diabetes, a deteriorated left ventricular relaxation and an increased left ventricular pressure in a rat model. Moreover, rats which are fed only a high fat diet, will develop the insulin resistance syndrome. This nongenetic rat model has the additional advantage of being easy to induce and can be used in the future to unravel the molecular mechanisms of DCM
Clinical benefit of rigorous atrioventricular delay optimisation in patients with a dual chamber pacemaker. The role of an interatrial conduction delay in left atrioventricular asynchrony.
No full textIn case of an interatrial conduction delay (IACD), the left ventricle will contract before the left atrial contraction has ended and the mitral valve will close prematurely. This leads to left atrioventricular dyssynchrony. An IACD is frequent in pacemaker patients, but often neglected during follow-up. Therefore, the atrioventricular delay (AVD) will be left at nominal values which are usually too short. Consequently, these patients develop left atrioventricular dyssynchrony, causing dizziness, fatigue and dyspnoea. This could be prevented by lengthening the AVD. Otherwise, some of the patients have a too long AVD, leading to a suboptimal diastolic filling time. In these patients, the optimal AVD could be achieved by shortening the delay.
Previous studies showed beneficial hemodynamic effects after AVD optimisation in cardiac resynchronisation therapy, biatrial and dual chamber pacemaker patients. We hypothesised that AVD optimisation would result in a better clinical outcome and left atrial function in dual chamber pacemaker patients.
We set up a randomised cross-over study in which we optimised the AVD via transthoracic echocardiography (TTE). The benefit of optimisation was evaluated through an ergospirometry, a 6 minute walk test, TTE, HeartQoL questionnaire, NYHA class and BNP.
Our study showed that individualised AVD optimisation by TTE improved the functional capacity and thus should be considered in every dual chamber pacemaker patient
Improving heart failure morbidity through individually tailored disease management
No full textHF is a complex clinical condition characterized by cardiac and non cardiac morbidity, with high morbidity and mortality and incremental costs for health care. The objective of this thesis was to investigate if optimal patient care through an individually tailored approach would lead to better outcomes. A first study was set up to assess the impact of RAS and ' blocker uptitration in HFrEF versus HFpEF patients after hospital admission; which concluded that uptitration of RAS blockers after a HF hospitalization is more feasible in younger patients with low co morbidity burden, and is an independent predictor of outcome in HFrEF but not HFpEF patients. Next to an optimal neurohumoral blocker therapy, elaborate HF care also comprises an extensive disease management program. A second study was set up to investigate the feasibility and impact of a hospital-wide, individually tailored and transmural disease management program in reducing ADHF and all-cause readmission rates and improving c
Improving heart failure morbidity through individually tailored disease management
No full textHF is a complex clinical condition characterized by cardiac and non cardiac morbidity, with high morbidity and mortality and incremental costs for health care. The objective of this thesis was to investigate if optimal patient care through an individually tailored approach would lead to better outcomes. A first study was set up to assess the impact of RAS and ' blocker uptitration in HFrEF versus HFpEF patients after hospital admission; which concluded that uptitration of RAS blockers after a HF hospitalization is more feasible in younger patients with low co morbidity burden, and is an independent predictor of outcome in HFrEF but not HFpEF patients. Next to an optimal neurohumoral blocker therapy, elaborate HF care also comprises an extensive disease management program. A second study was set up to investigate the feasibility and impact of a hospital-wide, individually tailored and transmural disease management program in reducing ADHF and all-cause readmission rates and improving c
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