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| ID | Type | Description | Link |
|---|---|---|---|
| TP/RE/12/22M-0073 | Other Identifier | National Research Ethics Committee of Tanta University |
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Assessment of the effect of gabapentin as an analgesic replacement on the Kidney function following Laparoscopic sleeve gastrectomy for Morbid Obese Patients by measuring two biomarkers: NGAL (Neutrophil gelatinase-associated lipocalin)and DKK3 (Dickkopf-3)
Obesity should be viewed as the number one preventable risk factor for kidney disease because obesity mediates the majority of diabetes and hypertension, the 2 major causes of end-stage kidney disease (ESKD). Morbidly obese adults have a 6-fold higher risk of diabetes compared with their lean peers.
Laparoscopic sleeve gastrectomy (LSG) has been approved since 2010, by both the American Society for Metabolic and Bariatric Surgery (ASMBS) and the American College of Surgeons (ACS) as an operation for the treatment of obesity and other obesity-related diseases.
Acute kidney injury (AKI) is one of the most common postoperative complications. It is a serious morbidity occurring during hospitalizations, and it is associated with prolonged hospital stay, high risk of in-hospital mortality, increased hospital costs, and decreased survival for up to 15 years after surgery. In addition, AKI increases the risk of incident and progressive chronic kidney disease and is associated with reduced long-term survival.
Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most common classes of medications used postoperatively. It is estimated that 1-5% of NSAIDs users may develop renal adverse effects, both AKI and CKD.
Gabapentin, an anticonvulsant widely used for the treatment of various neuropathic pain syndromes, has recently been investigated as an analgesic agent in the perioperative setting. Although it is not an analgesic itself, early experience suggests this medication can improve pain and reduce opioid requirements.
A new animal study shows that gabapentin demonstrated reno-protective properties against either acute or chronic kidney injury, primarily attributed to its antioxidant properties. Further clinical studies are required to validate and standardize therapeutic doses of gabapentin under investigation in patients susceptible or at risk of developing kidney dysfunction.
In this study, Neutrophil gelatinase-associated lipocalin (NGAL) and Dickkopf-3 (DKK3) will be biomarkers to assess kidney function. NGAL appears to be a promising marker for early detection of AKI and is likely to be adapted for wide-scale clinical use in patient management as a point-of-care test.
Measurement of DKK3 in urine represents a novel tool for the identification of patients at high risk for AKI regardless of the cause of kidney injury.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gabapentin + LSG | Experimental | 30 patients who will undergo LSG after receiving a single oral dose of Gabapentin 1200 mg, 1 hour prior to surgery. Blood and urine samples will be collected Just before the surgery, then 24 hrs. postoperatively. |
|
| Control | No Intervention | 30 patients who will neither undergo laparoscopic sleeve gastrectomy (LSG) nor receive any pharmacological treatment or placebo. Blood and urine samples will be collected just before the surgery, then 24 hrs postoperatively. | |
| LSG Only | Active Comparator | 30 patients who will undergo LSG without receiving any preoperative medication. Blood and urine samples will be collected Just before the surgery, then 24 hrs. postoperatively. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Laparoscopic Sleeve Gastrectomy | Procedure | Standard laparoscopic sleeve gastrectomy performed under general anesthesia according to institutional protocol, with gastric resection over a calibration bougie. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in renal function markers (serum creatinine and BUN) from baseline | Serum creatinine (mg/dL) and blood urea nitrogen, BUN (mg/dL) measured preoperatively (baseline) and at 24 hours after laparoscopic sleeve gastrectomy; primary analysis is the change from baseline to 24 hours postoperatively. | Baseline,24 hours postoperatively and 6 months after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Level of NGAL | Serum NGAL measured by ELISA kit | Baseline, 24 hours postoperatively and 6 months after surgery |
| Level of Dickkopf-3 (DKK3) | Serum and urine DKK3 measured by ELISA kit |
| Measure | Description | Time Frame |
|---|---|---|
| Change in lipid profile from baseline | Total cholesterol, LDL-C, HDL-C, and triglycerides measured preoperatively (baseline) and at 6 months postoperatively; change from baseline to 6 months. | Baseline and 6 months after surgery |
| Serum calcium level |
Inclusion Criteria:
Exclusion Criteria:
• Patients have advanced cancer on active treatment and end-stage renal, hepatic, and cardiopulmonary disease.
The ethical approval of the study will be obtained from by Medical research Ethics Committee of Tanta and Mansoura Universities and all participants will give their written consent.
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| Name | Affiliation | Role |
|---|---|---|
| Kholoud Salah Ibraahim Amin, Bsc. | Delta university for Sciences and Technology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tanta University | Tanta | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28214961 | Background | Kovesdy CP, Furth SL, Zoccali C; World Kidney Day Steering Committee. Obesity and kidney disease: hidden consequences of the epidemic. J Nephrol. 2017 Feb;30(1):1-10. doi: 10.1007/s40620-017-0377-y. | |
| 28423118 | Background | Kovesdy CP, Furth SL, Zoccali C. Obesity and kidney disease: hidden consequences of the epidemic. Braz J Med Biol Res. 2017 Apr 13;50(5):e6075. doi: 10.1590/1414-431X20166075. |
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| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| D009765 | Obesity |
| D011183 | Postoperative Complications |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D050110 | Bariatric Surgery |
| D000077206 | Gabapentin |
| ID | Term |
|---|---|
| D049088 | Bariatrics |
| D000073319 | Obesity Management |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
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Patients will be randomly allocated into three study groups. Group I (control group) will include 30 patients who will neither undergo laparoscopic sleeve gastrectomy (LSG) nor receive any pharmacological treatment or placebo.
Group II (Operation only) will consist of 30 patients who will undergo LSG without receiving any preoperative medication.
Group III (Operation+ treatment) will comprise 30 patients who will undergo LSG after receiving a single oral dose of Gabapentin 1200 mg ,1 hour prior to surgery.
Blood and urine samples will be collected Just before the surgery, then 24 hrs. postoperatively.
Blood and urine samples will be collected in follow-up, 6 months postoperatively.
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|
| gabapentin 1200 mg | Drug | A single oral dose of 1200 mg gabapentin administered 1 hour prior to induction of anesthesia for laparoscopic sleeve gastrectomy. The medication is given as two 600 mg tablets ((Unipharma Co.) |
|
|
| Baseline,24 hours postoperatively and 6 months after surgery |
Serum calcium (mg/dL) measured preoperatively (baseline) and at 24 hours after surgery to assess concomitant electrolyte/metabolic factors that may be associated with postoperative renal dysfunction.
| Baseline, 24 hours postoperatively and 6 months |
| Serum uric acid level | Serum uric acid (mg/dL) measured preoperatively (baseline) and at 24 hours after surgery to assess concomitant metabolic factors that may be associated with postoperative renal dysfunction. | Baseline,24 hours postoperatively and 6 months after surgery |
| 25789237 | Background | Hassani V, Pazouki A, Nikoubakht N, Chaichian S, Sayarifard A, Shakib Khankandi A. The effect of gabapentin on reducing pain after laparoscopic gastric bypass surgery in patients with morbid obesity: a randomized clinical trial. Anesth Pain Med. 2015 Feb 1;5(1):e22372. doi: 10.5812/aapm.22372. eCollection 2015 Feb. |
| 29108405 | Background | Rupniewska-Ladyko A, Malec-Milewska M, Kraszewska E, Pirozynski M. Gabapentin before laparoscopic sleeve gastrectomy reduces postoperative oxycodone consumption in obese patients: a randomized double-blind placebo-controlled trial. Minerva Anestesiol. 2018 May;84(5):565-571. doi: 10.23736/S0375-9393.17.12194-2. Epub 2017 Nov 6. |
| 30279273 | Background | Zewinger S, Rauen T, Rudnicki M, Federico G, Wagner M, Triem S, Schunk SJ, Petrakis I, Schmit D, Wagenpfeil S, Heine GH, Mayer G, Floege J, Fliser D, Grone HJ, Speer T. Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss. J Am Soc Nephrol. 2018 Nov;29(11):2722-2733. doi: 10.1681/ASN.2018040405. Epub 2018 Oct 2. |
| 24349249 | Background | Kim CS, Oak CY, Kim HY, Kang YU, Choi JS, Bae EH, Ma SK, Kweon SS, Kim SW. Incidence, predictive factors, and clinical outcomes of acute kidney injury after gastric surgery for gastric cancer. PLoS One. 2013 Dec 9;8(12):e82289. doi: 10.1371/journal.pone.0082289. eCollection 2013. |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010335 | Pathologic Processes |
| D000588 |
| Amines |
| D009930 | Organic Chemicals |
| D005680 | gamma-Aminobutyric Acid |
| D000613 | Aminobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |