RESUMO
Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
Assuntos
Cistatina C , Nefropatias , Humanos , Proteoma , Creatinina , Proteômica , Taxa de Filtração Glomerular/fisiologia , Nefropatias/diagnóstico , BiomarcadoresRESUMO
OBJECTIVES: The augmented inflammatory response to cardiac surgery is a recognized cause of postoperative acute kidney injury. The present study aimed to investigate the effects of preoperative cyclosporine treatment on cytokine production and delineate factors associated with postoperative kidney impairment. DESIGN: A randomized, double-blind, placebo-controlled, single-center study. SETTING: At a tertiary care, university hospital. PARTICIPANTS: Patients eligible for elective coronary artery bypass grafting surgery; 67 patients were enrolled. INTERVENTIONS: Patients were randomized to receive 2.5 mg/kg cyclosporine or placebo before surgery. Cytokine levels were measured after the induction of anesthesia and 4 hours after the end of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Tissue-aggressive (interleukin [IL]-1ß, macrophage inflammatory protein [MIP]-1ß, granulocyte colony-stimulating factor [G-CSF], IL-6, IL-8, IL-17, MCP-1), as well tissue-lenient (IL-4) cytokines, were significantly elevated in response to surgery. Changes in cytokine levels were not affected by cyclosporine pretreatment. CONCLUSIONS: Elective coronary artery bypass grafting surgery with cardiopulmonary bypass triggers cytokine activation. This activation was not impacted by preoperative cyclosporine treatment.
Assuntos
Ponte de Artéria Coronária , Ciclosporina , Ponte Cardiopulmonar , Ponte de Artéria Coronária/efeitos adversos , Ciclosporina/farmacologia , Citocinas/farmacologia , Humanos , Rim/fisiologiaRESUMO
BACKGROUND: Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation with prognostic value for elevated risk of morbidity and mortality. It has not yet been shown how the inflammatory process induced by cardiac surgery affects suPAR concentrations postoperatively. METHODS: In a prospective observational study, plasma suPAR levels were measured in 30 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), pre-, peri, post-operatively, and 3-5 days after surgery. Fifteen patients underwent coronary artery bypass grafting (CABG) and 15 underwent complex procedures with longer CPB duration. Concentrations of suPAR at each time point were compared to the preoperative levels and compared between the two groups. RESULTS: In both groups, plasma suPAR concentrations were significantly higher on the first postoperative day (3.27 (interquartile range (IQR) 2.75-3.86) µg/L compared to baseline (2.62 (1.98-3.86)) µg/L, p < .001. There were no significant differences in suPAR concentrations between the groups at any time point. Preoperatively, the median suPAR concentration was 2.57 (2.01-3.60) µg/L in the CABG group versus 2.67 (1.89-3.97) µg/L in the complex group (p = .567). At ICU arrival 2.48 (2.34-3.23) µg/L versus 2.73 (2.28-3.44) µg/L in CABG and complex patients, respectively (p = .914). There was no difference in suPAR concentrations between the groups on postoperative day 1 (3.34 (2.89-3.89) versus 3.19 (2.57-3.62) p = .967) or 3-5 days after surgery (2.72 (1.98-3.16) versus 2.96 (2.39-4.28) p = .085. CONCLUSIONS: After a transient rise on the first postoperative day, the suPAR levels returned to the preoperative levels by the third postoperative day. There was no significant difference in suPAR levels between the routine CABG and complex group with longer CPB time.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Biomarcadores , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Humanos , PrognósticoRESUMO
OBJECTIVES: To explore the preoperative, intraoperative, and postoperative dynamics of heparin-binding protein (HBP) in cardiothoracic surgery. DESIGN: This was a prospective, observational study. SETTING: The study was conducted at a single university hospital. PARTICIPANTS: Thirty patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) were included, 15 of whom underwent coronary artery bypass grafting surgery and 15 of whom underwent complex procedures. Ten patients undergoing lung surgery also were included as a conventional surgery reference group. INTERVENTIONS: No interventions were performed. MEASUREMENTS AND MAIN RESULTS: HBP was measured at nine different perioperative times. HBP levels increased immediately after heparin administration, further increased during CPB, but decreased rapidly after protamine administration. At arrival to the intensive care unit, median HBP levels were 24.8 (15.6-38.1) ng/mL for coronary artery bypass grafting patients and 51.2 (34.0-117.7) ng/mL for complex surgery patients (pâ¯=â¯0.011). One day after surgery, HBP levels in all three groups were below the proposed cutoff of 30 ng/mL, which previously was found to predict development of organ dysfunction in patients with infection. CONCLUSIONS: HBP levels are elevated by the administration of heparin and the use of CPB but reduced by protamine administration. At postoperative day one, HBP levels were less than the threshold for organ dysfunction in patients with infection. The usefulness of HBP for predicting postoperative infections in cardiothoracic surgery should be investigated in future studies.
Assuntos
Ponte Cardiopulmonar , Heparina , Peptídeos Catiônicos Antimicrobianos , Proteínas Sanguíneas , Humanos , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND: The optimal prime solution for the cardiopulmonary bypass (CPB) circuit in adult cardiac surgery has not yet been defined. Mannitol is widely used in the priming solution for CPB despite the fact that there is no clear consensus on the role of mannitol in cardiac surgery. The aim of this study was to investigate the effect of mannitol in the CPB prime solution. METHODS: This prospective, randomized, double-blind study included 40 patients with normal cardiac and renal functions, who underwent coronary artery bypass grafting. One group received a prime based on Ringer's acetate (n = 20), and the other a prime consisting of Ringer's acetate with 200 mL mannitol (n = 20). Changes in osmolality, acid-base status, electrolytes, and renal-related parameters were monitored. RESULTS: No significant differences were found in osmolality between the Ringer's acetate group and the mannitol group at any time. The mannitol group showed a pronounced decrease in sodium, from 138.7 ± 2.8 mmol/L at anaesthesia onset, to 133.9 ± 2.6 mmol/L after the start of CPB (P < .001). No differences were seen in the renal parameters between the groups, apart from a short-term effect of mannitol on peroperative urine production (P = .003). CONCLUSION: We observed no effects on osmolality of a prime solution containing mannitol compared to Ringer's acetate-based prime in patients with normal cardiac and renal function. The use of mannitol in the prime resulted in a short-term, significant decrease in sodium level.
Assuntos
Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária/métodos , Manitol/farmacologia , Idoso , Cloretos/análise , Método Duplo-Cego , Feminino , Humanos , Soluções Isotônicas , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Estudos Prospectivos , Sódio/análise , Equilíbrio HidroeletrolíticoRESUMO
Shrunken pore syndrome (SPS) is a condition in which estimated glomerular filtration rate (eGFR) based upon cystatin C is lower than eGFR based upon creatinine. It has been associated with increased mortality even in the presence of normal GFR in both a cardiac surgical population and a general population. No systematic studies of the variation in eGFRcystatin C/eGFRcreatinine-ratio used for SPS diagnosis have been published. This study aims to evaluate whether early and midterm mortality following elective cardiac surgery varies with the ratio used to identify SPS. Preoperative levels of cystatin C and creatinine were analysed in 4007 patients undergoing elective coronary artery bypass grafting (CABG) and/or surgical aortic valve replacement (sAVR). The eGFRcystatin C/eGFRcreatinine-ratio was calculated based on the equation pairs CKD-EPIcystatin C/CKD-EPIcreatinine and CAPA/LMrev. The overall 1- and 3-year all-cause mortality was 2.9 and 6.8%, respectively. Mean follow-up time was 3.6 years. Mortality markedly and progressively increased with a decrease in the eGFRcystatin C/eGFRcreatinine-ratio for both equation pairs. An increase in mortality was noted already when the ratio decreased from 1.0 to 0.90. To facilitate the clinical decisions based upon the SPS-defining eGFRcystatin C/eGFRcreatinine-ratio, we calculated both the ratios defining the highest combined sensitivity and specificity and the ratios producing a high specificity of 95%, finding different cut-off for these scenarios.
Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Curva ROC , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Sensibilidade e Especificidade , SíndromeRESUMO
BACKGROUND: Acute kidney injury is a common complication after cardiac surgery, leading to increased morbidity and mortality. One suggested cause for acute kidney injury is extracorporeal circulation-induced ischemia-reperfusion injury. In animal studies, cyclosporine has been shown to reduce ischemia-reperfusion injury in the kidneys. We hypothesized that administering cyclosporine before extracorporeal circulation could protect the kidneys in patients undergoing cardiac surgery. METHODS: The Cyclosporine to Protect Renal Function in Cardiac Surgery (CiPRICS) study was an investigator-initiated, double-blind, randomized, placebo-controlled, single-center study. The primary objective was to assess if cyclosporine could reduce acute kidney injury in patients undergoing coronary artery bypass grafting surgery with extracorporeal circulation. In the study, 154 patients with an estimated glomerular filtration rate of 15 to 90 ml · min · 1.73 m were enrolled. Study patients were randomized to receive 2.5 mg/kg cyclosporine or placebo intravenously before surgery. The primary endpoint was relative plasma cystatin C changes from the preoperative day to postoperative day 3. Secondary endpoints included biomarkers of kidney, heart, and brain injury. RESULTS: All enrolled patients were analyzed. The cyclosporine group (136.4 ± 35.6%) showed a more pronounced increase from baseline plasma cystatin C to day 3 compared to placebo (115.9 ± 30.8%), difference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001). The same pattern was observed for the other renal markers. The cyclosporine group had more patients in Risk Injury Failure Loss End-stage (RIFLE) groups R (risk), I (injury), or F (failure; 31% vs. 8%, P < 0.001). There were no differences in safety parameter distribution between groups. CONCLUSIONS: Administration of cyclosporine did not protect coronary artery bypass grafting patients from acute kidney injury. Instead, cyclosporine caused a decrease in renal function compared to placebo that resolved after 1 month.
Assuntos
Injúria Renal Aguda/epidemiologia , Ponte de Artéria Coronária/tendências , Ciclosporina/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Complicações Pós-Operatórias/epidemiologia , Cuidados Pré-Operatórios/métodos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/fisiopatologia , Idoso , Ponte de Artéria Coronária/métodos , Ciclosporina/efeitos adversos , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/fisiopatologia , Cuidados Pré-Operatórios/efeitos adversosRESUMO
Shrunken Pore Syndrome was recently suggested for the pathophysiologic state in patients characterized by an estimation of their glomerular filtration rate (GFR) based upon cystatin C, which is lower or equal to 60% of their estimated GFR based upon creatinine, i.e. when eGFR cystatin C ≤ 60% of eGFR creatinine. Not only the cystatin C level, but also the levels of other low molecular mass proteins are increased in this condition. The preoperative plasma levels of cystatin C and creatinine were measured in 1638 patients undergoing elective coronary artery bypass grafting. eGFR cystatin C and eGFR creatinine were calculated using two pairs of estimating equations, CAPA and LMrev, and CKD-EPI cystatin C and CKD-EPI creatinine, respectively. The Shrunken Pore Syndrome was present in 2.1% of the patients as defined by the CAPA and LMrev equations and in 5.7% of the patients as defined by the CKD-EPI cystatin C and CKD-EPI creatinine equations. The patients were studied over a median follow-up time of 3.5 years (2.0-5.0 years) and the mortality determined. Shrunken Pore Syndrome defined by both pairs of equations was a strong, independent, predictor of long-term mortality as evaluated by Cox analysis and as illustrated by Kaplan-Meier curves. Increased mortality was observed also for the subgroups of patients with GFR above or below 60 mL/min/1.73 m(2). Changing the cut-off level from 60 to 70% for the CAPA and LMrev equations increased the number of patients with Shrunken Pore Syndrome to 6.5%, still displaying increased mortality.
Assuntos
Ponte de Artéria Coronária/mortalidade , Cistatina C/sangue , Nefropatias/mortalidade , Idoso , Ponte de Artéria Coronária/efeitos adversos , Creatinina/sangue , Procedimentos Cirúrgicos Eletivos , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Estimativa de Kaplan-Meier , Nefropatias/diagnóstico , Nefropatias/etiologia , Glomérulos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , SíndromeRESUMO
BACKGROUND: To date, there are no known methods for preventing acute kidney injury after cardiac surgery. Increasing evidence suggests that erythropoietin has renal antiapoptotic and tissue protective effects. However, recent human studies have shown conflicting results. The authors aimed to study the effect of a single high-dose erythropoietin preoperatively on renal function after coronary artery bypass grafting in patients with preoperative impaired renal function. METHODS: This single-center, randomized, double-blind, placebo-controlled study included 75 patients scheduled for coronary artery bypass grafting with preexisting renal impairment estimated glomerular filtration rate based on p-cystatin C (<60 and >15 ml/min). The patients either received a single high-dose erythropoietin (400 IU/kg) or placebo preoperatively. The primary endpoint was renal protection evaluated by p-cystatin C at the third postoperative day compared to the preoperative values. Incidence of acute kidney injury and other renal biomarker changes were among secondary endpoints. RESULTS: There was no statistically significant difference on the third postoperative day for relative p-cystatin C level changes from baseline between the groups, 131 ± 31% (mean ± SD) for the study group and 125 ± 24% for the control group (P = 0.31; 95% CI, -0.6 to 20% for the difference). There were no statistically significant differences in other renal biomarkers or measures between the groups (p-neutrophil gelatinase-associated lipocalin, p-creatinine, p-urea, and estimated glomerular filtration rate). There were no other differences in outcome variables between the groups. CONCLUSION: Intravenous administration of a single high-dose (400 IU/kg) erythropoietin did not have a renal protective effect on patients with reduced kidney function undergoing coronary artery bypass surgery.
Assuntos
Injúria Renal Aguda/prevenção & controle , Ponte de Artéria Coronária/efeitos adversos , Eritropoetina/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes/uso terapêuticoRESUMO
Cardiothoracic surgery using cardiopulmonary bypass (CPB) triggers an inflammatory state that may be difficult to differentiate from infection. Heparin-binding protein (HBP) is a candidate biomarker for sepsis. As data indicates that HBP normalizes rapidly after cardiothoracic surgery, it may be a suitable early marker of postoperative infection. We therefore aimed to investigate which variables influence postoperative HBP levels and whether elevated HBP concentration is associated with poor surgical outcome. This exploratory, prospective, observational study enrolled 1475 patients undergoing cardiothoracic surgery using CPB, where HBP was measured at ICU arrival. Patients with HBP in the highest tercile were compared to remaining patients. Multivariable logistic regressions were performed to identify factors predictive of elevated HBP and 30-day mortality. Overall median HBP was 30.0 ng/mL. Patients undergoing isolated CABG or surgery with CPB-duration ≤ 60 min had a median HBP of 24.9 ng/mL and 23.2 ng/mL, respectively. Independent predictors of elevated postoperative HBP included increased EuroSCORE, prolonged CPB-duration and high intraoperative temperature. Increased HBP was an independent predictor of 30-day mortality. This study confirms the promising characteristics of HBP as a biomarker for identification of postoperative sepsis, especially after routine procedures. Further studies are required to investigate whether HBP may detect postoperative infections.
Assuntos
Ponte Cardiopulmonar , Sepse , Humanos , Ponte Cardiopulmonar/efeitos adversos , Estudos Prospectivos , Biomarcadores , Sepse/diagnóstico , Complicações Pós-OperatóriasRESUMO
Renal dysfunction is a major risk factor for premature death and has been studied extensively. A new renal syndrome, shrunken pore syndrome (SPS), confers higher mortality in all studied populations. SPS is a condition in which cystatin C-based estimation of glomerular filtration rate (eGFRcystatin C) is ≥ 60% than creatinine-based estimation of glomerular filtration rate (eGFRcreatinine). We aimed to study the impact of SPS on mortality in a cohort of patients with follow up of up to 10 years. This was a retrospective single centre cohort study. We enrolled 3993 consecutive patients undergoing elective cardiac surgery. Outcome was evaluated using Kaplan Meier analysis and multivariable Cox regression. 1-, 5- and 10-year survival for patients with SPS was 90%, 59% and 45%, and without SPS 98%, 88% and 80% (p < 0.001). SPS was found to be an independent predictor for mortality with an HR of 1.96 (95% CI 1.63-2.36). SPS negatively affected survival regardless of pre-operative renal function. SPS is an independent predictor for mortality after elective cardiac surgery, equal to or greater than risk factors such as diabetes, impaired left ventricular function or renal dysfunction. SPS affected mortality even in patients with normal eGFR.Clinical registration number: ClinicalTrials.gov, ID NCT04141072.
Assuntos
Cistatina C , Nefropatias , Humanos , Creatinina , Eliminação Renal , Estudos de Coortes , Estudos RetrospectivosRESUMO
OBJECTIVE: Decreased kidney function increases cardiovascular risk and predicts poor survival. Estimated glomerular filtration rate (eGFR) by creatinine may theoretically be less accurate in the critically ill. This observational study compares long-term cardiovascular mortality risk by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation; Caucasian, Asian, paediatric and adult cohort (CAPA) cystatin C equation and the CKD-EPI combined creatinine/cystatin C equation. METHODS: The nationwide study includes 22 488 intensive care patients in Uppsala, Karolinska and Lund University Hospitals, Sweden, between 2004 and 2015. Creatinine and cystatin C were analysed with accredited methods at admission. Reclassification and model discrimination with C-statistics was used to compare creatinine and cystatin C for cardiovascular mortality prediction. RESULTS: During 5 years of follow-up, 2960 (13 %) of the patients died of cardiovascular causes. Reduced eGFR was significantly associated with cardiovascular death by all eGFR equations in Cox regression models. In each creatinine-based GFR category, 17%, 19% and 31% reclassified to a lower GFR category by cystatin C. These patients had significantly higher cardiovascular mortality risk, adjusted HR (95% CI), 1.55 (1.38 to 1.74), 1.76 (1.53 to 2.03) and 1.44 (1.11 to 1.86), respectively, compared with patients not reclassified. Harrell's C-statistic for cardiovascular death for cystatin C, alone or combined with creatinine, was 0.73, significantly higher than for creatinine (0.71), p<0.001. CONCLUSIONS: A single cystatin C at admission to the intensive care unit added significant predictive value to creatinine for long-term cardiovascular death risk assessment. Cystatin C, alone or in combination with creatinine, should be used for estimating GFR for long-term risk prediction in critically ill.
Assuntos
Doenças Cardiovasculares , Insuficiência Renal Crônica , Adulto , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Criança , Creatinina , Cuidados Críticos , Estado Terminal , Cistatina C , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Insuficiência Renal Crônica/epidemiologiaRESUMO
Decreased glomerular filtration rate (GFR) is linked to poor survival. The predictive value of creatinine estimated GFR (eGFR) and cystatin C eGFR in critically ill patients may differ substantially, but has been less studied. This study compares long-term mortality risk prediction by eGFR using a creatinine equation (CKD-EPI), a cystatin C equation (CAPA) and a combined creatinine/cystatin C equation (CKD-EPI), in 22,488 patients treated in intensive care at three University Hospitals in Sweden, between 2004 and 2015. Patients were analysed for both creatinine and cystatin C on the same blood sample tube at admission, using accredited laboratory methods. During follow-up (median 5.1 years) 8401 (37%) patients died. Reduced eGFR was significantly associated with death by all eGFR-equations in Cox regression models. However, patients reclassified to a lower GFR-category by using the cystatin C-based equation, as compared to the creatinine-based equation, had significantly higher mortality risk compared to the referent patients not reclassified. The cystatin C equation increased C-statistics for death prediction (p < 0.001 vs. creatinine, p = 0.013 vs. combined equation). In conclusion, this data favours the sole cystatin C equation rather than the creatinine or combined equations when estimating GFR for risk prediction purposes in critically ill patients.
Assuntos
Creatinina/sangue , Cuidados Críticos , Cistatina C/sangue , Mortalidade , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVES: To evaluate serum creatinine (s-creatinine) and serum cystatin C (s-cystatin C) levels and estimated glomerular filtration rate (eGFR) at different time points as predictors for mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS: A total of 1638 patients undergoing elective CABG were studied prospectively over a median follow-up of 3.5 years (range, 2.0-5.0 years). Renal function was assessed by a comparison of s-creatinine, s-cystatin C values measured preoperatively and at the lowest postoperative level of renal function. The eGFR was estimated by different formulas: Modification of Diet in Renal Disease, the 2009 Chronic Kidney Disease Epidemiology (CDK-EPI) for s-creatinine, the 2012 CKD-EPI formula for s-cystatin C, the 2012 CKD-EPI formula for s-cystatin C and s-creatinine in combination, and the Caucasian Asian, Pediatric, and Adult subjects formula for s-cystatin C. Cox proportional hazards model analysis and C-statistics were used to evaluate independent predictors of mortality and to assess the predictive ability of the different renal function measures. RESULTS: The 30-day mortality was 0.8%. Overall survival was 96.1% ± 0.4% at 2 years and 90.0% ± 1.2% at 5 years. Preoperative s-cystatin C showed greater predictive power than s-creatinine for overall mortality (area under the curve, 0.794 vs 0.653). Preoperative s-cystatin C (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.36-1.99) and eGFR based on s-cystatin C (HR, 0.96; 95% CI, 0.95-0.98), were both independent predictors of mortality. The unadjusted HR for mortality comparing the lowest preoperative cystatin C quintile (Q1) with Q4-Q5 were as follows: Q1 versus Q5, HR, 2.0; 95% CI, 1.6-2.5 (P < .001); Q1 versus Q4, HR, 1.6; 95% CI, 1.2-2.2 (P = .005). CONCLUSIONS: The s-cystatin C level and s-cystatin C-based eGFR measured preoperatively are strong predictors for mortality after elective CABG.
Assuntos
Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/cirurgia , Cistatina C/sangue , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Insuficiência Renal Crônica/mortalidade , Idoso , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etiologia , Suécia/epidemiologia , Fatores de TempoRESUMO
OBJECTIVE: To examine the mortality risk of blood transfusions when donor information, postdonation treatment, and a wide selection of risk factors are taken into account. METHODS: A retrospective study was performed on 9907 patients who underwent coronary artery bypass grafting and/or aortic valve replacement. Several transfusion-related risk factors, including age of blood products, sex of donor, ABO group, Rh group, posttransfusion treatment, and sex matching, were included in the analysis. A wide selection of preoperative comorbidities were included as well. A Cox proportional hazards analysis was performed to determine significant risk factors. Patients were followed for a period of up to 12 years posttransfusion. RESULTS: We found an excess mortality for transfusions of sex-mismatched red blood cells (RBCs) per unit transfused (hazard ratio [HR], 1.083; 95% confidence interval [CI] 1.028-1.140; P = .003). In addition, we found a significant risk during the first year for transfusing 1 to 2 units of non-leukocyte-depleted RBCs (HR, 1.426; 95% CI, 1.004-2.024; P = .047). Transfusion of 1 to 2 units of leukocyte-depleted RBCs was not associated with increased risk (HR, 0.981; 95% CI, 0.866-1.110; P = not significant). The age of blood products was not associated with increased mortality. CONCLUSIONS: In this large retrospective study, transfusion of non-sex-matched RBCs was associated with increased mortality. In addition, in patients receiving small amounts of blood, leukocyte depletion of RBCs had a beneficial effect on patient survival.
Assuntos
Sistema ABO de Grupos Sanguíneos , Doadores de Sangue , Procedimentos Cirúrgicos Cardíacos/mortalidade , Previsões , Reação Transfusional , Idoso , Contagem de Eritrócitos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida/tendências , Suécia/epidemiologiaRESUMO
INTRODUCTION: Acute kidney injury (AKI) after cardiac surgery is common and results in increased morbidity and mortality. One possible mechanism for AKI is ischaemia-reperfusion injury caused by the extracorporeal circulation (ECC), resulting in an opening of the mitochondrial permeability transition pore (mPTP) in the kidneys, which can lead to cell injury or cell death. Ciclosporin may block the opening of mPTP if administered before the ischaemia-reperfusion injury. We hypothesised that ciclosporin given before the start of ECC in cardiac surgery can decrease the degree of AKI. METHODS AND ANALYSIS: Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS) study is an investigator-initiated double-blind, randomised, placebo-controlled, parallel design, single-centre study performed at a tertiary university hospital. The primary objective is to assess the safety and efficacy of ciclosporin to limit the degree of AKI in patients undergoing coronary artery bypass grafting surgery. We aim to evaluate 150 patients with a preoperative estimated glomerular filtration rate of 15-90â mL/min/1.73â m2. Study patients are randomised in a 1:1 ratio to receive study drug 2.5â mg/kg ciclosporin or placebo as an intravenous injection after anaesthesia induction but before start of surgery. The primary end point consists of relative P-cystatin C changes from the preoperative day to postoperative day 3. The primary variable will be tested using an analysis of covariance method. Secondary end points include evaluation of P-creatinine and biomarkers of kidney, heart and brain injury. ETHICS AND DISSEMINATION: The trial is conducted in compliance with the current version of the Declaration of Helsinki and the International Council for Harmonisation (ICH) Good Clinical Practice guidelines E6 (R1) and was approved by the Regional Ethical Review Board, Lund and the Swedish Medical Products Agency (MPA). Written and oral informed consent is obtained before enrolment into the study. TRIAL REGISTRATION NUMBER: NCT02397213; Pre-results.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Ponte de Artéria Coronária/efeitos adversos , Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Complicações Pós-Operatórias/tratamento farmacológico , Cuidados Pré-Operatórios/métodos , Injúria Renal Aguda/etiologia , Biomarcadores , Creatinina/sangue , Método Duplo-Cego , Taxa de Filtração Glomerular/efeitos dos fármacos , Hospitais Universitários , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Proteínas de Transporte da Membrana Mitocondrial/efeitos dos fármacos , Poro de Transição de Permeabilidade Mitocondrial , Complicações Pós-Operatórias/prevenção & controle , Estudo de Prova de Conceito , Traumatismo por Reperfusão/prevenção & controle , Projetos de Pesquisa , SuéciaRESUMO
OBJECTIVE: This study relates long-term mortality after cardiac surgery to different methods of measuring postoperative renal function, classified according to the Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. The dynamics of acute kidney injury during hospital stay were studied by comparing renal function preoperatively, at its poorest measurement, and at discharge. METHODS: A total of 5746 patients undergoing coronary artery bypass grafting were studied in a Cox analysis, over a median follow-up time of 6.0 years (range, 2.5-9.5 years). Renal function was determined using the highest and discharge levels of plasma creatinine by Cockroft-Gault and Modification of Diet in Renal Disease formulae. Acute kidney injury was classified according to the RIFLE criteria. Renal recovery was studied in a 2-dimensional matrix, and the impact of renal function at different time points was related to survival. RESULTS: Although the p-creatinine classified most patients in the nonacute kidney injury and Risk class; the Cockroft-Gault and Modification of Diet in Renal Disease formulae classified more patients in Injury and Failure classes; and higher Risk, Injury, and Failure classes were associated with increased long-term mortality. The effect of renal recovery on long-term survival was only in part associated with improved outcome. In addition, the poorest renal function was a stronger predictor of mortality compared with preoperative and discharge levels. CONCLUSIONS: Classification using RIFLE criteria seems to be useful because it detects patients with renal impairment that affects long-term survival. The Modification of Diet in Renal Disease method seems to be the most robust method when predicting outcome, and the poorest renal function was the best predictor of outcome. Renal recovery was generally associated with better outcome.
Assuntos
Injúria Renal Aguda/mortalidade , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/cirurgia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Idoso , Biomarcadores/sangue , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Estimativa de Kaplan-Meier , Rim/fisiopatologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Modelos de Riscos Proporcionais , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Suécia/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Patients undergoing cardiac surgery often require transfusions of red blood cells, plasma and platelets. These components differ widely in both indications for use and composition. However, from a statistical point of view there is a significant colinearity between the components. This study explores the relation between the transfusion of different blood components and long-term mortality. METHODS: A retrospective single-centre study was performed including 5,261 coronary artery bypass grafting patients, excluding patients receiving more than eight units of red blood cells, those suffering early death (7 days) and emergency cases. Patients were followed up for a period of up to 7.5 years. A broad spectrum of potential risk factors was analysed using Cox proportional hazards survival regression. Non-significant risk factors were removed by step-wise elimination, and transfusion of red blood cells, plasma and platelets was forced to remain in the model. RESULTS: The transfusion of red blood cells was not associated with decreased long-term mortality (HR = 1.007, p = 0.775), whereas the transfusion of plasma was associated with decreased long-term survival (HR = 1.060, p < 0.001), and the transfusion of platelets was associated with increased long-term survival (HR = 0.817, p = 0.011). The risk associated with transfusion of plasma was mainly attributed to patients receiving large amounts of plasma. All hazard ratios are per unit of blood product transfused. CONCLUSIONS: No association was found between the transfusion of red blood cells and mortality during the study period. However, transfusion of plasma was associated with increased mortality while transfusion of platelets was associated with decreased mortality during the study period.