The goal of this clinical trial is to learn if ursodeoxycholic acid, also called UDCA, can help protect kidney function in adults undergoing partial nephrectomy for kidney tumors. It will also learn about the safety of UDCA when used around the time of surgery. Before the randomized part of the study begins, the first 6 participants will receive UDCA in a safety run-in phase. These participants will be closely monitored for side effects, laboratory abnormalities, and other medical problems to assess the preliminary safety and tolerability of perioperative UDCA administration. If no unacceptable safety concerns are identified, the study will proceed to the randomized, placebo-controlled phase. The main questions this study aims to answer are: 1. Is perioperative UDCA administration safe in patients undergoing surgery for renal tumors? 2. Does UDCA lower the risk of acute kidney injury within 48 hours after partial nephrectomy? 3. Does UDCA reduce the decline in kidney function after surgery? 4. Does UDCA increase blood levels of UDCA and related bile acids during the perioperative period? 5. What medical problems do participants have when taking UDCA around the time of surgery? 6. Researchers will also evaluate whether UDCA affects urinary biomarkers of kidney injury. Researchers will compare UDCA with a placebo, a look-alike substance that contains no active drug, to see if UDCA can help protect the kidney from ischemia-reperfusion injury during partial nephrectomy. Participants will: 1. Take UDCA or a placebo three times a day from 2 days before surgery until 5 days after surgery. 2. Undergo partial nephrectomy as planned by their treating surgeon. 3. Have blood tests before and after surgery to check kidney function, liver function, and bile acid levels. 4. Participants will provide urine samples before and after surgery for the assessment of kidney injury biomarkers. 5. Be monitored for side effects, surgical complications, and other medical problems during hospitalization and follow-up.
Partial nephrectomy (PN) is the preferred nephron-sparing surgical approach for T1 renal tumors, providing oncological outcomes comparable to those of radical nephrectomy while better preserving renal function. However, temporary renal artery clamping during PN may induce renal ischemia-reperfusion injury (IRI), thereby increasing the risk of postoperative acute kidney injury and long-term renal functional decline. Currently, no pharmacological intervention has been proven to provide definitive and effective perioperative renal protection in patients undergoing PN. Ursodeoxycholic acid (UDCA), an endogenous bile acid, has a well-established safety profile and good clinical accessibility. Previous studies in experimental models of kidney injury have shown that UDCA may exert renoprotective effects through mechanisms including amelioration of mitochondrial dysfunction, attenuation of oxidative stress and inflammatory responses, and improvement of impaired fatty acid oxidation. This study aims to evaluate whether perioperative administration of UDCA can attenuate renal injury caused by ischemia-reperfusion during PN. In addition, by monitoring renal function, liver function, bile acid levels, and relevant kidney injury biomarkers, this study will comprehensively assess the efficacy and safety of perioperative UDCA administration, thereby providing evidence for its potential application in perioperative renal protection in kidney surgery. Before the randomized phase begins, the first six enrolled patients will receive UDCA treatment and will be observed and evaluated as part of a safety run-in phase. Participants in this phase will be included in the safety analysis but will not be included in the final efficacy analysis of the randomized phase. If no unacceptable safety risks are identified during the safety run-in phase, the study will proceed to the randomized, double-blind, placebo-controlled phase. After completion of the safety analysis, investigators will screen all patients scheduled to undergo PN at the time of hospital admission. Patients who meet the eligibility criteria and voluntarily agree to participate in the study will be randomized after providing written informed consent.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
146
Ursodeoxycholic Acid Capsules 250 mg, 1 capsule tid. UDCA will be administered orally three times daily, starting 2 days before surgery and continuing through postoperative day 5.
1 capsule tid. Placebo will be administered orally three times daily, starting 2 days before surgery and continuing through postoperative day 5.
Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing
Nanjing, Jiangsu, China
RECRUITINGIncidence of AKI within 48 hours after surgery
Defined according to the serum creatinine criterion of the KDIGO criteria
Time frame: From baseline to 48 hours after surgery.
Incidence of AKI within 48 hours after surgery(Defined according to either the serum creatinine or urine output criterion of the KDIGO criteria)
Defined according to either the serum creatinine or urine output criterion of the KDIGO criteria
Time frame: From baseline to 48 hours after surgery.
Between-group difference in mean eGFR on postoperative day 1
This endpoint will be assessed using an analysis of covariance model
Time frame: From baseline to 24 hours after surgery.
Between-group difference in mean eGFR on postoperative day 2
This endpoint will be assessed using an analysis of covariance model
Time frame: From baseline to 48 hours after surgery.
Maximum absolute increase in serum creatinine from baseline within 48 hours after surgery
Maximum absolute increase = highest postoperative serum creatinine within 48 hours - baseline serum creatinine
Time frame: From baseline to 48 hours after surgery.
Perioperative complications
Assessed according to the Clavien-Dindo classification
Time frame: Perioperatively
UDCA-related adverse events
Including gastrointestinal reactions, hepatobiliary abnormalities, skin reactions, and allergic reactions
Time frame: From the first administration of the study drug until 7 days after the last administration.
Change From Baseline in ALT and AST Levels
Change from baseline in ALT and AST levels will be calculated as the ALT or AST value at postoperative assessment time point minus the corresponding baseline value.
Time frame: Perioperatively
Between-group difference in mean affected-kidney eGFR at 6 months after surgery
This endpoint will be assessed using an analysis of covariance model.
Time frame: at 6 months after surgery
Acute Ipsilateral Renal Dysfunction spectrum score (AIRD)
Time frame: at 6 months after surgery
Ischemia Recovery Index (IRI)
Time frame: at 6 months after surgery
Affected-kidney eGFR recovery rate
Time frame: at 6 months after surgery
Incidence of a ≥25% decline from baseline in eGFR within 1 year after surgery
Time frame: Baseline to 1 year after surgery
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