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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group aminophylline | Active Comparator | 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) |
|
| Group frusemide | Placebo Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| aminophylline | Drug | 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) |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yanding Gao | Contact | 13917337835 | masa_oreo@yeah.net | |
| Haiyan Wang | Contact | 18930174845 | mgul@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Xuemin Wang, PhD | Shanghai 6th People's Hospital | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11437769 | Background | Parker MR, Willatts SM. A pilot study to investigate the effects of an infusion of aminophylline on renal function following major abdominal surgery. Anaesthesia. 2001 Jul;56(7):670-5. doi: 10.1046/j.1365-2044.2001.01374.x. | |
| 23055869 | Background | Lynch BA, Gal P, Ransom JL, Carlos RQ, Dimaguila MA, Smith MS, Wimmer JE Jr, Imm MD. Low-dose aminophylline for the treatment of neonatal non-oliguric renal failure-case series and review of the literature. J Pediatr Pharmacol Ther. 2008 Apr;13(2):80-7. doi: 10.5863/1551-6776-13.2.80. |
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| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D000628 | Aminophylline |
| D005665 | Furosemide |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D005029 | Ethylenediamines |
| D003959 | Diamines |
| D011073 | Polyamines |
| D000588 | Amines |
| D009930 |
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| frusemide | Drug | Use frusemide with Syringe pumps,maximum dose to 15mg/h |
|
| normal saline | Drug | Placebo bolus followed by IV infusions of normal saline (0.9%) every hour (matched by volume and appearance to the treatment group) |
|
| Change from central venous pressure at 2 weeks |
| 27500627 | Background | Yang GZ, Xue FS, Liu GP, Sun C. Use of Aminophylline to Prevent Acute Kidney Injury After Pediatric Cardiac Surgery. Pediatr Crit Care Med. 2016 Aug;17(8):814. doi: 10.1097/PCC.0000000000000838. No abstract available. |
| 24247300 | Background | Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, Bart BA, Bull DA, Stehlik J, LeWinter MM, Konstam MA, Huggins GS, Rouleau JL, O'Meara E, Tang WH, Starling RC, Butler J, Deswal A, Felker GM, O'Connor CM, Bonita RE, Margulies KB, Cappola TP, Ofili EO, Mann DL, Davila-Roman VG, McNulty SE, Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM; NHLBI Heart Failure Clinical Research Network. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA. 2013 Dec 18;310(23):2533-43. doi: 10.1001/jama.2013.282190. |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| Organic Chemicals |
| D013806 | Theophylline |
| D014970 | Xanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D013424 | Sulfanilamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D000814 | Aniline Compounds |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |