Oxidative Stress and Circulating Nuclear DNA (cfDNA) in Acute Kidney Injury and Continuous Renal Replacement Therapies. Effect of Two Anticoagulation Strategies of the Extracorporeal Purification System in Renal Function Recovery.
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Recovery of renal function
研究概览
简要总结
Acute kidney injury (AKI) is the inability of the kidneys to perform their functions of purifying and cleaning the blood. It is a frequent complication in hospitalized patients, especially in those admitted to the ICUs. In these situations is common to use machines to artificially and temporarily replace renal function so waste products that can be toxic are removed from the body.
The purpose of this study is to assess the effectiveness and safety of two anticoagulation strategies of the extracorporeal purification system in critically ill patients with acute kidney injury treated with continuous renal replacement therapy (CRRT) evaluating the effect of both strategies in oxidative stress and extracellular nucleosomes and its influence on the recovery of renal function.
详细描述
Acute kidney injury (AKI) is defined as a sudden deterioration of renal function that causes loss of electrolyte control, acid base status and fluid balance, with subsequent accumulation of nitrogenous waste products that should be eliminated by the kidney. It is a frequent complication in hospitalized patients, especially those admitted to Intensive Care Units (ICUs). Its etiology is usually multifactorial, usually in the context of multiorgan dysfunction syndrome (MODS). The epidemiology and risk factors associated with its development, as well as the type of treatment that these patients are currently undergoing, continues to be the subject of debate, given the impact it has on morbidity and mortality.
To temporary substitute renal function in critically ill patients continuous renal replacement therapies (CRRT) are frequently used. The classification and nomenclature of techniques depends on the duration, continuity and operational characteristics of the treatment system. Thus, we distinguish between continuous techniques and intermittent techniques. Peritoneal dialysis (PD) is rarely used in developed countries for the treatment of AKI in ICU. Intermittent hemodialysis (IHD) is the most frequently used technique, although its use in ICU has considerable limitations on fluid balance, uremia control and elimination of medium molecular weight molecules.
Due to the enormous difficulty of obtaining studies with the necessary statistical power to provide the degree of evidence needed to clarify questions regarding the indications, modalities and other technical aspects of the CRRT, it is commonly used the experience that both the clinical practice in chronic patients as the results of scientific research that intermittent techniques (IHD fundamentally) confers to the clinician.
In patients with IHD, certain conditions are associated with a worse prognosis and an increased risk of mortality. These can include cardiovascular diseases, diabetes mellitus (DM), atherosclerosis, infectious processes, malnutrition, inflammation, oxidative stress, iron deficiency, anemia, calcification, uremia and volume overload. AKI requiring a renal replacement technique (RRT) represents an independent risk factor for mortality in critically ill patients. Oxidative stress and inflammation play important roles in the initiation and extension phases of AKI, as well as in causing injury to distant organs after AKI.
In CRRT to prevent coagulation of the extracorporeal system requires the use of some method of anticoagulation. The most frequent anticoagulation strategies include systemic heparin and regional citrate administration. However, some undesirable effects of CRRT may affect the patient's outcome, including the risks of systemic bleeding and membrane biocompatibility induced by anticoagulants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult intensive care patients (age > 18) admitted to the ICU with AKI requiring treatment with continuous renal replacement technique.
- •Patients able to accept being included in the study by signing the Informed Consent (IC). If the patient can not give consent, family consent is requested and, by default, the opinion of the person of trust or designated decision, if present. If there is no family present, trusted person or legal representative designated, the possibility of deferred consent is not contemplated. In this case the patient will not be included in the study.
排除标准
- •Age under 18 years old.
- •Pregnancy and/or lactation.
- •Terminal diseases or life expectancy lower than 48 hours.
- •Increased risk of bleeding (defined as platelet count less than 40x109 / L, partial thromboplastin time (TTPA) over 60 seconds, prothrombin time (PT)international normalized ratio (INR) greater than 2.0 or recent major bleeding).
- •Need of systemic anticoagulation therapy.
- •Contraindication for heparin.
- •Heparin-induced Thrombocytopenia (HIT).
- •Dialysis in the 24 hours prior to inclusion.
- •Hypercalcemia (> 3 mmol / L).
- •Severe Hepatitis: glutamic oxaloacetic transaminase (GOT) or glutamic pyruvic transaminase (GPT) > 1000 IU / L.
- •Cirrhosis.
- •Inclusion in another research protocol.
研究组 & 干预措施
Heparin
Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein.
The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the heparin arm the anticoagulation technique to be used will be non-fractional heparin.
Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration [Ci]) and postfilter (outlet filter plasma concentration [Co]) sites of the extracorporeal circulation circuit at different times.
干预措施: Central venous access (Procedure)
Heparin
Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein.
The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the heparin arm the anticoagulation technique to be used will be non-fractional heparin.
Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration [Ci]) and postfilter (outlet filter plasma concentration [Co]) sites of the extracorporeal circulation circuit at different times.
干预措施: Pump-assisted circuit (Device)
Heparin
Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein.
The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the heparin arm the anticoagulation technique to be used will be non-fractional heparin.
Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration [Ci]) and postfilter (outlet filter plasma concentration [Co]) sites of the extracorporeal circulation circuit at different times.
干预措施: Heparin sodium (Drug)
Heparin
Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein.
The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the heparin arm the anticoagulation technique to be used will be non-fractional heparin.
Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration [Ci]) and postfilter (outlet filter plasma concentration [Co]) sites of the extracorporeal circulation circuit at different times.
干预措施: Blood and ultrafiltrate samples (Procedure)
Citrate
Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein.
The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the citrate arm regional citrate anticoagulation of the extracorporeal purification system will be used to avoid coagulation of the circuit.
Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration [Ci]) and postfilter (outlet filter plasma concentration [Co]) sites of the extracorporeal circulation circuit at different times.
干预措施: Central venous access (Procedure)
Citrate
Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein.
The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the citrate arm regional citrate anticoagulation of the extracorporeal purification system will be used to avoid coagulation of the circuit.
Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration [Ci]) and postfilter (outlet filter plasma concentration [Co]) sites of the extracorporeal circulation circuit at different times.
干预措施: Pump-assisted circuit (Device)
Citrate
Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein.
The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the citrate arm regional citrate anticoagulation of the extracorporeal purification system will be used to avoid coagulation of the circuit.
Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration [Ci]) and postfilter (outlet filter plasma concentration [Co]) sites of the extracorporeal circulation circuit at different times.
干预措施: Regional citrate anticoagulation (Other)
Citrate
Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein.
The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the citrate arm regional citrate anticoagulation of the extracorporeal purification system will be used to avoid coagulation of the circuit.
Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration [Ci]) and postfilter (outlet filter plasma concentration [Co]) sites of the extracorporeal circulation circuit at different times.
干预措施: Blood and ultrafiltrate samples (Procedure)
结局指标
主要结局
Recovery of renal function
时间窗: Through study completion, an average of 20 days.
Impact of circulating nuclear DNA (cfDNA) and oxidative stress on change of Creatinine from baseline to hospital discharge.
次要结局
- Mortality(Day 90 after ICU admission)
- Activation and elimination of free radicals(24 hours)
- Activation and elimination of biomarkers of inflammation(24 hours)
- Activation and elimination of biomarkers of cell damage(24 hours)
- Mass transfer and clearance of free radicals(24 hours)
- Mass transfer and clearance of biomarkers of inflammation(24 hours)
- Mass transfer and clearance of biomarkers of cell damage(24 hours)
- Length of stay(From hospital admission until the date of documented hospital discharge or date of death from any cause, whichever came first, assessed up to 90 days)
研究者
Fernando Sanchez
Consultant of Intensive Care Medicine
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana