Assessment of Dialysis Initiation by a Fuzzy Mathematics Equation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the impact of the optimal and late initiation of dialysis on the mortality and quality of life in end-stage renal disease (ESRD) patients by the Dialysis Initiation based on Fuzzy mathematics Equation (DIFE), which is a novel equation for the assessment of timing of dialysis initiation established by Fuzzy mathematics.

Detailed Description
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The optimal time of dialysis initiation is still controversial. Estimated glomerular filtration rate (eGFR) which is now widely used as the assessment of timing of dialysis is lack of specificity. Some clinical factors such as heart failure, volume overload, malnutrition also determine the dialysis time. But these subjective judgements do not have a standard. So there is no quantitative assessment of timing of dialysis initiation. The research team developed a novel equation named DIFE (Dialysis Initiation based on Fuzzy mathematics Equation) with data from a retrospective multicenter cohort by fuzzy mathematical methods to combine these clinical factors and lab indexes. The DIFE was confirmed to be more accurate and convenient to use in clinical practice than eGFR only at the assessment of dialysis initiation time in the internal validation. For further validation of the DIFE, the team will conduct a multicenter randomized controlled trial. Patients who need hemodialysis will be randomized to optimal start dailysis group or late start dailysis group by the assessment of the DIFE. Based on the comparison of the two groups, this trial will provide evidence for the optimal timing of dialysis initiation in patients with end-stage renal disease by the DIFE.

Official Title
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Impact on Mortality of Timing of Dialysis Initiation in Patients With End-stage Renal Disease by a Novel Assessment Based on Fuzzy Mathematics

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Other: optimal start time
* Other: late start time


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have progressive chronic kidney disease with an eGFR less than 15 ml/min/1.73m2 and a DIFE between 30-35 Expected to commence maintenance hemodialysis as their renal replacement treatment Agreeable to randomization Exclusion Criteria: Acute kidney injury (AKI) or AKI on chronic kidney disease (CKD) With the primary disease of systemic lupus erythematosus (SLE) or systemic vasculitis Have received or planning to receive a kidney transplant or peritoneal dialysis during the study Has a recently diagnosed cancer that was likely to affect survival (except for the following cases: the cancer has been confirmed to be cured or relieved for over 5 years, have had the radical resection for the basal cell carcinoma or squamous carcinoma of skin or carcinoma in-situ of any part of the body ) Hepatocirrhosis Positive test of Human Immunodeficiency Virus (HIV), the hepatitis B virus antigen (HBsAg) or anti-hepatitis C virus antibody (HCV Ab) Acute infection within 1 month Bad habit which is difficult to withdrawal such as alcohol abuse Poor compliance and could not be treated according to the protocol Being pregnant, nursing or having a plan for pregnancy Life expectancy less than 1 year The investigator confirm that should not enroll in the study with any other cases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: optimal start dialysis group<br>The DIFE will be used as the assessment of initiation time of dialysis. Patients in this group will start dialysis when their results of the DIFE reaching to 30-35, which defined as the optimal start time. | Other: optimal start time<br>* patients will start hemodialysis when their DIFE reach 35, and can not wait if the DIFE decline to 30.<br>|
| Active Comparator: late start dialysis group<br>the DIFE will be used as the assessment of initiation time of dialysis. Patients in this group will start dialysis when their results of the DIFE less than 30, which defined as late start time. | Other: late start time<br>* patients will start hemodialysis when their DIFE less than 30<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all-cause mortality | proportion of patients who die from any cause | from the date of enrollment until the end of study, assessed up to 3 years | 
| cerebro-cardiovascular mortality | proportion of patients who die from cerebro-cardiovascular disease | 3 years, from the date of enrollment until the end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cerebro-cardiovascular events | proportion of patients who suffer from cardiovascular events, which include nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack,new-onset angina, acute heart failure or severe arrhythmia. | from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years | 
| hospitalization | proportion of patients admitted to hospital | from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years | 
| Nutrition assessment | assess the patient's nutritional status by subjective global assessment (SGA) assessment and serum albumin level | from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years | 
| the change of quality of life | use short form-36 reported by the patients to assess the patient's quality of life | from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years | 
| Medical cost | the cost by the patient, family and insurance during treatment | from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years | 
| Hemodialysis complications | the proportion of patients who suffer from hemodialysis complications including blood assess revise, assess infection, severe fluid and electrolyte disorders | from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years | 
| cognitive dysfunction | assess cognitive dysfunction by Montreal Cognitive Assessment (MoCA) | from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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end-stage renal disease, timing of dialysis initiation, hemodialysis, fuzzy mathematics, glomerular filtration rate