Effects of Aminophylline on Renal Function and Urine Volume of AKI Patient

Study Overview
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Brief Summary
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This study evaluates the effects of aminophylline on serum creatinine and urine volume of AKI Patient.Half of participants will receive aminophylline and furosemide in combination,while the other half will receive only furosemide.

Detailed Description
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Acute kidney injury (AKI) is a sudden perturbation of kidney function that is frequently associated with high morbidity and mortality rates . A diagnostic time limit of 48 hours was recently introduced to ensure early diagnosis, management and prevention of progression to irreversible renal function loss . Furthermore, early AKI biomarkers that can ensure prompt diagnosis have been identified. When these biomarkers become widely available to clinical practice, informed therapeutic interventions capable of aborting disease progression, morbidity and mortality multiplication can be applied . In the injured kidney, adenosine is released endogenously from the macula densa causing vasoconstriction of the renal afferent arterioles via the adenosine A1receptor as well as vasodilatation of the renal efferent arterioles via the adenosine A2 receptor; thereby reducing the renal blood flow and glomerular perfusion pressure leading to ischemic kidney injury . One measure that has been tried with the objective of achieving better AKI outcome is the use of aminophylline (an ethylenediamine coupled theophylline) . Aminophylline is converted to theophylline in the human body, which in turn vasodilates the renal afferent arterioles through competitive inhibition of adenosine on the adenosine A1 receptor. Aminophylline and theophylline, methylxanthine nonselective adenosine receptor antagonists, have been effective in the management of AKI in certain clinical scenarios including heart failure, calcineurin inhibitor toxicity, and perinatal asphyxia. In the kidney, adenosine constricts the afferent arteriole and decreases glomerular blood flow; adenosine receptor blockade mitigates this vasoconstriction. Aminophylline also inhibits phosphodiesterase at higher concentrations, which leads to increased urine output. Eligible subjects included all patients more than 18 years old with acute kidney injury in ICU. To ensure the safest oversight for the duration of the study drug infusion, the investigators only approached patients for consent if participants' ICU stay would likely be at least 72 hours . Patients were recruited in the preoperative clinic or in the inpatient ward/ICU; the nature of the consent process for this interventional drug trial necessitated that all procedures were elective or scheduled. Because aminophylline has been associated with tachycardia and seizures at high serum levels, and its metabolism may be affected by liver or thyroid dysfunction and sepsis, the investigators selected the following exclusion criteria: history of tachyarrhythmias, seizures, coagulopathy (international normalized ratio > 1.5 while not taking warfarin),or hypothyroidism. Study investigators or research nurses recruited participants; written, informed consent was signed by each patient or guardian. The treatment group received aminophylline 5 mg/kg IV load over 30 minutes, followed by 0.5 mg/kg IV every hour, for 72 hours .The control group received placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group), for 72 hours.

Official Title
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Effects of Aminophylline on Renal Function and Urine Volume Acute Kidney Injury Patient

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Drug: aminophylline
* Drug: frusemide
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute injury (AKI) with no lack of circulating volume (central venous pressure >8cmH2O) Exclusion Criteria: Patients with chronic kidney disease Patients with acute renal injury caused by insufficient circulating volume Patients who do not cooperate with the use of the drug therapy Patients who do not cooperate with the relevant examination

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group aminophylline<br>To increase the dose of frusemide until 15mg/h with Syringe pumps. If the urine doesn't reach 1ml/kg/h,then combined with Aminophylline(loading dose of 5mg/kg，and maintenance dose of 0.5mg/kg) | Drug: aminophylline<br>* To increase the dose of frusemide until 15mg/h with Syringe pumps. If the urine doesn't reach 1ml/kg/h,then combined with Aminophylline(loading dose of 5mg/kg，and maintenance dose of 0.5mg/kg)<br>Drug: frusemide<br>* Use frusemide with Syringe pumps,maximum dose to 15mg/h<br>|
| Placebo Comparator: Group frusemide<br>Use frusemide with Syringe pumps,maximum dose to 15mg/h，with placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group) | Drug: frusemide<br>* Use frusemide with Syringe pumps,maximum dose to 15mg/h<br>Drug: normal saline<br>* Placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum creatinine |  | Change from serum creatinine at 2 weeks | 
| urine volume |  | Change from urine volume at 2 weeks | 
| Serum cystatin-C |  | Change from Serum cystatin-C at 2 weeks | 
| Urine β_2-microglobulin |  | Change from Urine β_2-microglobulin at 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dose of norepinephrine |  | Change from dose of norepinephrine at 2 weeks | 
| blood pressure |  | Change from baseline systolic blood pressure at 2 weeks | 
| central venous pressure |  | Change from central venous pressure at 2 weeks |