Multidiscipline Care for Acute Kidney Disease (AKD) (AKD)

Multidiscipline Care for Acute Kidney Injury to Chronic Kidney Disease Transition (Acute Kidney Disease) - a Randomized Controlled Study

The incidence rate of acute kidney injury (AKI) in hospitalized patients is increasing, and the mortality associated with dialysis-requiring AKI remains as high as 60-70%. In these patients, AKI results are increased in-hospital and post-hospitalization medical resource utilization. To improve AKI-associated morbidity and mortality, Taiwan Consortium of Acute Kidney Injury and Renal Diseases (CAKS, TCTC) as the leading clinical trial group of kidney diseases in Asia-Pacific will establish an anonymous nationwide AKI database to explore the epidemiology, risk factors and prognosis of AKI in Taiwan. The demographic and clinical information of AKI stage 2, 3 or weaning from dialysis requiring AKI patients (AKI-D), will be prospectively collected for further analysis. In this double two-by-two factorial design, upon the identification of AKI stage 2, 3 or weaning from AKI-D at index out patients clinics, enrollees who are randomly assigned to slow kidney function progression first by randomization to add Angiotensin-Converting Enzyme Inhibitors (ACE-I)/Angiotensin II Receptor Blocker (ARB), or by randomization to multidisciplinary care. Patients will be followed up at least 6 months to evaluate kidney function and the predictability of developing chronic kidney disease, end stage renal disease, major cardiovascular events and mortality.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: never received RAAS blockers or received RAAS blockers before AKI.

Detailed Description

Acute kidney injury is an emerging syndrome in the past 10 years. Among hospital diagnosed kidney disease, acute renal disease outnumbered chronic kidney disease (CKD) since 2005, and the incidence is still climbing. Patients who were diagnosed with AKI bear a substantial risk for adverse outcomes, including premature death, increased morbidity, prolonged hospitalization, and increased medical costs. A variety of factors may predispose a patient to AKI, including poor pre-morbid kidney reserve, conditions leading to hemodynamic instability, or increased complexity of concurrent medications. With the advance of modern medical diagnosis and treatment modalities, the incidence and prevalence of AKI syndrome gradually increase over the past years.

The KDIGO Guideline for AKI recommended that we should diagnose AKI if a given patient has a 6 hour urine amount less than 0.5ml/kg/hr or a serum creatinine elevates more than 0.3mg/dL or 1.5 times greater than baselines. Epidemiology data on hospitalized patients indeed disclosed high risk for adverse events using this classification system and its analogues. However, besides diagnosis, we do not have a useful tool to treat or to help improve patient outcomes Acute kidney injury (AKI) is a common complication that affects nearly 5% of hospitalized patients and 40%-70% of patients in the intensive care unit. AKI requiring dialysis (AKI-D), the most severe type of AKI, is associated with the highest proportion of morbidity and mortality. AKI is associated with a risk of end-stage renal disease (ESRD) that is 13 times as high as the risk among patients without AKI, and the risk of ESRD is 40 times as high if the patients have both AKI and pre-existing chronic kidney disease (CKD). Since AKI is recognized as a risk factor for the development of ESRD, it is crucial to have appropriate protection strategies for the avoidance of further target organ damage and associated mortality in the critical phases of the acute kidney disease (AKD). Several studies have validated the hypothesis proposed by Guyton that the kidneys have a crucial role in affecting the chronic level of blood pressure (BP). Furthermore, AKI during hospitalization was an independent risk factor for subsequent development of BP elevation. BP level is related to the risk of cardiovascular disease and death, which makes the elevated BP as a leading risk factor for global health. However, it is still a missing puzzle piece in the timely pharmacologic treatment and long-term target organ protection of AKD patients. By retrospective analysis of the large FROG ICU database, including 1551 ICU survivors, of which 611 had AKI during their ICU stay, the authors could demonstrate reduced 1-year mortality in the cohort who had AKI and who were prescribed ACEIs/ARBs.

To address the issue of the 'black hole' between AKI and CKD, the Kidney Disease: Improving Global Outcomes (KDIGO) AKI Workgroup propose the concept of acute kidney disease (AKD). AKD, defined as a glomerular filtration rate (GFR) <60 ml/min/1.73 m2 or evidence of structural kidney damage for <3 months, provides an operationally integrated bridge between AKI and CKD. The AKD concept, which incorporates the concept of partial renal recovery, might also help raise awareness and engender the necessary clinical mechanisms to follow AKI survivors for progression to CKD, which has been recently highlighted as a missed opportunity for adequate transitions of care. Also, a panel of gut microbiota and biomarkers will also be determined.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vincent Wu, doctor; Phone Number: 886-937-223-278; Email: dr.vincentwu@gmail.com

Study Locations

• Taiwan
  • Kaohsiung, Taiwan
    • Not yet recruiting
    • Kaohsiung Medical University Hospital
    • Contact: SHANG-JHIH HUANG
  • Keelung, Taiwan
    • Recruiting
    • Keelung CGMH
    • Contact: Heng-Chih Pan
    • Principal Investigator: Heng-Chih Pan
  • Taichung, Taiwan
    • Recruiting
    • China Medical University Hospital
    • Contact: Ya-Fei Yang
    • Principal Investigator: Ya-Fei Yang
    • Sub-Investigator: Ping-Chin Lai
  • Taichung, Taiwan
    • Recruiting
    • Taichung Veterans General Hospital
    • Contact: Ming-Ju Wu
    • Principal Investigator: Ming-Ju Wu
    • Sub-Investigator: JYUN-DE HUANG
  • Taipei, Taiwan
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Der-Cherng Tarng
    • Principal Investigator: Der-Cherng Tarng
    • Sub-Investigator: GUO-HUA LI
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Vincent Wu, doctor; Phone Number: 886-937223278; Email: dr.vincentwu@gmail.com
  • Taoyuan, Taiwan
    • Recruiting
    • Linkou Chang Gung Memorial Hospital
    • Contact: CHIH-HSIANG CHANG
    • Principal Investigator: CHIH-HSIANG CHANG
    • Sub-Investigator: JI-TSENG FANG
    • Sub-Investigator: YUNG-CHANG CHEN
    • Sub-Investigator: HSIANG-HAO HSU
    • Sub-Investigator: MING JEN CHAN
    • Sub-Investigator: KUAN-HSING CHEN
    • Sub-Investigator: CHENG-HAO WENG
    • Sub-Investigator: HUANG-YU YANG
    • Sub-Investigator: Ching Chung Hsiao
    • Sub-Investigator: MING-YANG CHANG
    • Sub-Investigator: CHAN-YU LIN
    • Sub-Investigator: WEN-HUNG HUANG
    • Sub-Investigator: TSUNG-YU TSAI
    • Sub-Investigator: CHING-WEI HSU
    • Sub-Investigator: YA-CHUNG TIAN
    • Sub-Investigator: YI-JUNG LI
    • Sub-Investigator: CHANG-CHI CHENG
    • Sub-Investigator: LI-CHENG WU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 20 years old on the day of index discharge
2. AKI develops during admission, as defined with KDIGO-AKI Guideline, namely, elevation of serum creatinine above 0.3mg/dL within two days, above 1.5 times baseline and ever receives dialysis during this index hospitalization.
3. Patients who has KDIGO-AKI stage 2, 3 or who could wean from dialysis requiring AKI-D in the index hospitalization.

Exclusion Criteria:

1. Baseline estimated glomerular filtration rates (eGFR) less than 5ml/min/1.73m2 or greater than 90ml/min/1.73m2 according to MDRD equation after index discharge.
2. Patients receive further re-dialysis within 90 days after index hospital discharge, who are withdrawal for AKI-D. (sensors)
3. Previous gastrointestinal operations.
4. Patients with major hemorrhage, as defined with acute hemorrhage and requirement of blood transfusion during index admission.
5. Patients with a chronic lung disease requiring non-invasive or invasive positive pressure ventilation.
6. Solid organ or hematological transplantation donors.
7. Evidence of obstructive acute kidney injury.
8. Systolic blood pressure < 110mmHg.
9. Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: never received RAAS blockers or multidiscipline consultation before AKI.; The enrollees assigned to the control group should not receive RAAS blockers or AKD consultation at least in 180 days after index discharge. In addition, these multidiscipline consultation and administration of RAAS blockers are continuing, and results regarding them remain masked. All patients provided written informed consent.	Drug: never received RAAS blockers or received RAAS blockers before AKI.; Enrollees who are not received renin-angiotensin-aldosterone blockers (RAAS) are randomly assigned to slow kidney function progression by adding RAAS blockers by receiving at least defined daily dose equal to Losartan 50mg or Captopril 25mg bid. The acute kidney disease (AKD) consultation should be transferred at least one time within 90 days after index hospital discharge after withdrawing from dialysis requiring AKI (AKI-D). All enrolled patients are randomly referred to receive comprehensive multidiscipline consultation targeting a glycated hemoglobin level of less than 7.0%, systolic blood-pressure, target, <130 mm Hg, low density lipid (LDL) less than 100mg/dL and control of hyperuricemia less than 7.2mg/deal in male as well as 6.1mg/dl in females. We suggest to adherence to low protein diet achieve the goal of hemoglobin more than 11g/L at 180 day after index discharge.; Other Names: Multidiscipline consultation
Active Comparator: had received RAAS blockers and multidiscipline consultation before AKI.; All enrolled patients are randomly referred to receive comprehensive multidiscipline consultation targeting a glycated hemoglobin level of less than 7.0%, systolic blood-pressure, target, <130 mm Hg, low density lipid (LDL) less than 100mg/dL and control of hyperuricemia less than 7.2mg/deal in male as well as 6.1mg/dl in females. We suggest to adherence to low protein diet achieve the goal of hemoglobin more than 11g/L at 180 day after index discharge. Enrollees who are not received renin-angiotensin-aldosterone blockers (RAAS) are randomly assigned to slow kidney function progression by adding RAAS blockers by receiving at least defined daily dose equal to Losartan 50mg or Captopril 25mg bid. The acute kidney disease (AKD) consultation should be transferred at least one time within 90 days after index hospital discharge after withdrawing from dialysis requiring AKI (AKI-D).	Drug: never received RAAS blockers or received RAAS blockers before AKI.; Enrollees who are not received renin-angiotensin-aldosterone blockers (RAAS) are randomly assigned to slow kidney function progression by adding RAAS blockers by receiving at least defined daily dose equal to Losartan 50mg or Captopril 25mg bid. The acute kidney disease (AKD) consultation should be transferred at least one time within 90 days after index hospital discharge after withdrawing from dialysis requiring AKI (AKI-D). All enrolled patients are randomly referred to receive comprehensive multidiscipline consultation targeting a glycated hemoglobin level of less than 7.0%, systolic blood-pressure, target, <130 mm Hg, low density lipid (LDL) less than 100mg/dL and control of hyperuricemia less than 7.2mg/deal in male as well as 6.1mg/dl in females. We suggest to adherence to low protein diet achieve the goal of hemoglobin more than 11g/L at 180 day after index discharge.; Other Names: Multidiscipline consultation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal replacement therapy at any time after dialysis	Patients will followed up at any time after dialysis.	MAKE at 180 days
survival	Patients will followed up at any time after death.	MAKE at 180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rehospitalization	Rehospitalization from myocardial infarction, heart failure, arrhythmia, invasive cardiovascular interventions, cardiovascular causes after noncardiovascular surgery, stroke.	MAKE at 180 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Vincent Wu, doctor, NTUH

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2019
• Primary Completion (Anticipated): February 15, 2023
• Study Completion (Anticipated): February 15, 2024

Study Registration Dates

• First Submitted: June 11, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): October 1, 2021
• Last Update Submitted That Met QC Criteria: September 23, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Chronic kidney disease; Acute kidney disease
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Acute Kidney Injury
• Other Study ID Numbers: 201811079MINC; 201900796A3C502 (Other Identifier: Chang Gung Medical Foundation Institutional Review Board)

Drug and device information, study documents

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