Impact of Glycemic Control After Reperfusion on Acute Kidney Injury in Living Donor Liver Transplantation

Impact of Glycemic Control After Reperfusion on Acute Kidney Injury in Living Donor Liver Transplantation: A Propensity Score-matched Analysis

This retrospective cohort study of patients classified by the blood glucose level after reperfusion in liver transplantation repicient. Our object is to investigate whether controlling BG levels within the optimal range during neohepatic phase is associated with a reduction of AKI incidence. Furthermore, severe AKI, chronic kidney disease (CKD), major adverse cardiac event (MACE) and mortality were also investigated.

Study Overview

• Status: Completed
• Conditions: End Stage Liver Disease; Hyperglycemia; Hypoglycemia; Acute Kidney Injury
• Intervention / Treatment: Other: Observational study, records of blood glucose level after reperfusion

Detailed Description

The detrimental impact of glucose instability including hyper- and hypoglycemia on postoperative outcomes has been well-established in various fields, particularly in cardiac surgery, and intensive care unit settings. Also, glucose instability occurs frequently in liver transplantation (LT) surgery, attributed to factors such as insulin resistance, surgical stress, and onset of gluconeogenesis after reperfusion of the newly transplanted graft. Previous reports have demonstrated that hyperglycemia is associated with increased mortality, a higher incidence of graft rejection, and surgical site infection in LT. Alongside hyperglycemia, it is also important to consider hypoglycemia, given its association with adverse outcomes.

Acute kidney injury (AKI) stands as one of the most common and critical complications following LT, impacting extended duration of hospital stay, increased morbidity, and mortality. Although the etiology of AKI after LT is multifactorial, perioperative hyper- and hypoglycemia have also been suggested as potential risk factors for postoperative AKI. However, a recent study only has demonstrated that increased glucose variability, rather than hyper-and hypoglycemia alone, is associated with postoperative AKI after LT. The contradictory results observed to date may be attributed to differences in the definition of hyperglycemia, reflecting the challenges in determining the optimal blood glucose (BG) level in LT. In our study, the optimal BG level was determined according to the most recently updated and professional guidelines on glycemic control.

Identifying the timing for glycemic control during LT is also as crucial as determining the optimal BG level. BG levels reach their peak in the neohepatic phase and begin to decrease 3 hours after reperfusion. This excessively elevated hyperglycemia is due to glucose influx from the grafted liver, in addition to peripheral insulin resistance, and gradually decreases after successful LT. Therefore, maintaining a well-controlled BG level within the optimal range, especially during the neohepatic phase, may be associated with better outcomes after transplantation.

Our object is to investigate whether controlling BG levels within the optimal range during neohepatic phase is associated with a reduction of AKI incidence. Furthermore, severe AKI, chronic kidney disease (CKD), major adverse cardiac event (MACE), and mortality were also investigated.

• Study Type: Observational
• Enrollment (Actual): 3790

Contacts and Locations

Study Locations

• Korea, Republic of
  • Song-pa Gu
    • Seoul, Song-pa Gu, Korea, Republic of, 05500
      • Jun-Gol Song

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

living donor liver transplant recipients at Asan Medical Center, Seoul, Korea, Republic of Korea, from January 2008 to December 2019.

Description

Inclusion Criteria:

• Living donor liver transplantation recipients

Exclusion Criteria:

• The exclusion criteria were as follows: recipients under 18 years old, recipients who had undergone deceased donor liver transplantation, recipients who had undergone re-transplantation, recipients with impaired renal function such as CKD or HRS, or those with insufficient data

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 110 < REP BG < 180; Those with blood glucose levels over 110 and under 180 after reperfusion in liver transplantation recipients.	Other: Observational study, records of blood glucose level after reperfusion; Analyzes blood glucose level after reperfusion by dividing it into two groups: those with blood glucose levels between 110 and 180 and those with blood glucose levels below 110 or above 180.
Group REP BG ≤110 or ≥180; Those with blood glucose levels below 110 or above 180 after reperfusion in liver transplantation recipients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of acute kidney injury	determined by change in sCr according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition (increase in sCr of ≥26.5 mmol litre-1 within 48h or ≥1.5 times baseline within 7 days after surgery)	within 7 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of severe AKI	Severe AKI was defined as KIDIGO stage 2 or 3	within 7 days after surgery
incidence of chronic kidney disease (CKD)	when renal function assessed by calculating estimated serum glomerular filtration using the abbreviated modification of diet in renal disease equation was <60 mL/min/1.73 m2 for 3 months or more, irrespective of cause	within 1 year after surgery
incidence of Major adverse cardiac event (MACE)	MACE was defined including myocardial infarction (MI), atrial fibrillation (AF), pulmonary thromboembolism (PTE), heart failure (HF), cardiac arrest, and/or stroke	within postoperative 30 days (POD30)
overall mortality	overall mortality	the mortality at overall period (calculated from the date of surgery to the last follow-up) from the date of surgery (up to 10 years)

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Actual): August 29, 2020
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Liver Diseases; End Stage Liver Disease; Hyperglycemia; Wounds and Injuries; Hypoglycemia; Acute Kidney Injury
• Other Study ID Numbers: 2020-0675

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No