Goal-directed Hemodynamic Management and Kidney Injury After Radical Nephrectomy

Acute Kidney Injury Clinical Trial

Official title:

Impact of Goal-directed Hemodynamic Management on Occurrence of Acute and Persistent Kidney Injury After Radical Nephrectomy: A Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05149196
• Other study ID #: 2021-417
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 30, 2024
• Est. completion date: December 30, 2034

Study information

• Verified date: June 2024
• Source: Peking University First Hospital
• Contact: Dong-Xin Wang, MD,PhD
• Phone: 86 10 83572784
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Radical nephrectomy is a common operation for the treatment of renal cell carcinoma. However, acute kidney injury frequently occurs after surgery. And the occurrence of acute kidney injury is associated with an increased risk of chronic kidney disease. Intraoperative hypotension is identified as an important risk factor of postoperative acute kidney injury. Preliminary studies showed that goal-directed hemodynamic management may reduce kidney injury after surgery but requires further demonstration. We hypothesized that goal-directed hemodynamic management combining hydration, inotropes, and forced diuresis to maintain pulse pressure variation <9%, mean arterial pressure ≥85 mmHg, and urine flow rate >200 ml/h (3ml/kg/h) may reduce the incidence of acute kidney injury and improve long-term renal outcome after radical nephrectomy. The purpose of this study is to investigate the effect of goal-directed hemodynamic management on the occurrence of acute and persistent kidney injury in patients following radical nephrectomy.

Description:

Renal cancer accounts for 20.3% of urinary system tumors, and the incidence is still increasing. Surgical resection is the main treatment of renal cancer; radical nephrectomy is the standard operation for renal cancer of stage T2 or above. Acute kidney injury (AKI) is a common complication after radical nephrectomy, with an incidence of up to 53.9%. AKI is associated with the development of chronic kidney disease (CKD) and is an independent risk factor of new onset CKD in patients without underlying kidney disease. A meta-analysis showed that, at one year after surgery, patients with AKI had a 2.7-fold increased risk of new onset or progression of CKD and a 4.8-fold increased risk of end-stage renal disease. Moreover, even mild AKI is associated with renal insufficiency at 1 to 2 years after surgery.

Taking active measures to reduce the incidence of AKI may improve long-term renal function after radical nephrectomy. Many clinical studies show that intraoperative hypotension is an important risk factor of postoperative kidney injury. For example, a study found that intraoperative mean arterial pressure (MAP) <65 mmHg or a decrease of more than 20% from baseline was associated with an increased risk of postoperative AKI; the risk of AKI increased alone with prolonged duration of hypotension. However, recent randomized controlled trials showed inconsistent results regarding the effect of tight blood pressure management strategy on kidney outcome. Relevant studies indicated that hydration with forced diuresis and inotropes to maintain cardiac output and blood pressure might improve renal outcome.

In a previous pilot trial of the authors, goal-directed hemodynamic management combining hydrationa and inotropics reduced the incidence of AKI by about 40% in patients following partial nephrectomy. However, the difference was not statistically significant due to insufficient sample size. The purpose of this trial is to investigate whether goal-directed intraoperative hemodynamic management combining hydration, inotropics, and forced diuresis can reduce the occurrence of acute and persistent kidney injury in patients undergoing radical nephrectomy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1724
• Est. completion date: December 30, 2034
• Est. primary completion date: December 30, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Age of 18 years or older;

2. Scheduled to undergo radical nephrectomy for renal cancer.

Exclusion criteria

1. Diagnosed with chronic kidney disease stage 4 or stage 5 (GFR<30 ml/min/1.73m2) before surgery;

2. Uncontrolled severe hypertension (systolic blood pressure =180 mmHg or diastolic blood pressure =110 mmHg);

3. Combined with cardiovascular diseases with Revised Cardiac Risk Index (RCRI) >1 or metabolic equivalents (METs) <4;

4. Unable to communicate due to severe dementia, language barrier, or end-stage disease before surgery;

5. Other conditions that are considered unsuitable for inclusion (specific reasons should be indicated).

Related Conditions & MeSH terms

• Acute Kidney Injury
• Carcinoma, Renal Cell
• Chronic Kidney Diseases
• Hemodynamic Management
• Kidney Diseases
• Nephrectomy
• Renal Cell Carcinoma
• Renal Insufficiency, Chronic
• Wounds and Injuries

Intervention

Other:
• Targeted hemodynamic management
During anesthesia, hemodynamic managements include active hydration (>10 ml/kg/h), use of inotropes (dobutamine), and forced diuresis; the targets are to maintain pulse pressure variation <9%, mean arterial pressure =85 mmHg, and urine output >200 ml/h (3ml/kg/h). During the first 48 hours after surgery, systolic blood pressure is maintained =110 mmHg or within 20% of baseline by delaying antihypertensive resumption, providing fluid challenge, and/or vasoactive infusion.
• Routine care
During anesthesia, hemodynamic managements are conducted according to routine practice and usually include fluid infusion at a rate of 6-8 ml/kg/h without inotropics; the targets are to maintain mean arterial pressure =65 mmHg and urine output >0.5 ml/kg/h. During the first 48 hours after surgery, hemodynamic management is performed according to routine practice.

Locations

Country	Name	City	State
China	Beijing University First Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

References & Publications (32)

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* Note: There are 32 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	AKI stage within 7 days after surgery	Acute kidney injury is diagnosed and classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.	Up to 7 days after surgery
Other	Proportion of patients admitted in intensive care unit after surgery	Proportion of patients admitted in intensive care unit after surgery.	Up to 30 days after surgery
Other	Incidence of other major postoperative complications	Major postoperative complications are defined as new-onset medical conditions that are harmful to patients' recovery and required therapeutic intervention, i.e., grade 2 or higher on the Clavien-Dindo classification.	Up to 30 days after surgery
Other	Length of hospital stay after surgery	Length of hospital stay after surgery	Up to 30 days after surgery
Other	Prevalence of neurocognitive disorder at 6 months and 1 year after surgery	Neurocognitive disorder is defined as a decrease of neurocognitive function score of 1 standard deviation (SD) or more from baseline. Neurocognitive function is assessed with the Montreal Cognitive Assessment-telephone version (T-MoCA; score ranges from 0 to 22, with higher score indicating better cognitive function).	At 6 months and 1 year after surgery
Other	Quality of life at 6 months and 1 year after surgery	Quality of life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF), a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.	At 6 months and 1 year after surgery
Other	Overall survival time	Time interval from the end of surgery to all-cause death.	Up to 2 years after surgery
Primary	Incidence of acute kidney injury (early primary outcome)	Acute kidney injury is diagnosed and classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Acute kidney injury of stage 1 or above is defined as occurrence of acute kidney injury.	Up to 7 days after surgery
Primary	Time to new-onset or progression of chronic kidney disease (CKD) (long-term primary outcome).	New-onset CKD is defined as a decrease of glomerular filtration rate to <60 ml/min/1.73 m2 and persists for more than 3 months. Progression of CKD is defined as a decrease of glomerular filtration rate of 40% or more from baseline and persists for more than 3 months.	Up to 2 years after surgery
Secondary	Incidence of myocardial injury after noncardiac surgery (MINS) within 7 days after surgery	MINS is diagnosed according to the Fourth Universal Definition of Myocardial Infarction (2018).	Up to 7 days after surgery
Secondary	Incidence of delirium within 7 days after surgery	Delirium is assessed twice daily with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM).	Up to 7 days after surgery
Secondary	Incidence of surgical site infection within 30 days after surgery	Surgical site infection is diagnosed according to predefined definition.	Up to 30 days after surgery
Secondary	Incidence of CKD within 3 months after surgery	Included new-onset or progression of CKD. New-onset CKD is defined as a decrease of glomerular filtration rate to <60 ml/min/1.73 m2 and persists for more than 3 months. Progression of CKD is defined as a decrease of glomerular filtration rate of 40% or more from baseline and persists for more than 3 months.	Up to 3 months after surgery
Secondary	Proportion of various grades of CKD at different timepoints	CKD is diagnosed and classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.	Up to 2 years after surgery
Secondary	Event-free survival	Time interval from the end of surgery to new-onset or progression of CKD, serious events (required hospitalization or reoperation), or all-cause death, which ever come first. New-onset CKD is defined as a decrease of glomerular filtration rate to <60 ml/min/1.73 m2 and persists for more than 3 months. Progression of CKD is defined as a decrease of glomerular filtration rate of 40% or more from baseline and persists for more than 3 months.	Up to 2 years after surgery