Very Low Protein Diet and Renal Death in Chronic Kidney Disease (CKD)-ERIKA Study

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the use of a very low protein diet is effective in delaying the start of chronic dialysis treatment in patients affected by chronic kidney disease (CKD).

Detailed Description
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The prevalence of chronic dialysis patients is increasing worldwide because of the rising incidence of end stage renal disease, it is burdened by high cardiovascular risk, it is associated with a very high morbidity and mortality and it determines enormous costs for the community. The improvement in the management of metabolic and cardiovascular complication associated to chronic kidney disease (CKD) since the early stages of the disease becomes mandatory in order to delay the start of dialysis and to ameliorate the whole patient outcome. Dietary protein restriction represents a basic therapeutic approach in CKD, by reducing the accumulation of nitrogen catabolic substances, the phosphorus retention and the consequent hyperparathyroidism, the metabolic acidosis, the salt intake and the consequent hypertension, the proteinuria, and by improving the anemia and the glycemic tolerance, but the effects of the low protein diet on renal failure progression rate have not been definitely demonstrated. Dietary effective reduction of just 0.2 g/kg/day of proteins is effective in ameliorating blood urea nitrogen, metabolic acidosis and hyperphosphoremia, and the very low protein diet (VLPD) allows a further improving of the metabolic control of uremia, it is safe, not affecting the nutritional status, and it is cost saving. VLPD has been suggested to delay the start of renal replacement therapy with respect to standard low protein diet, by mean of either secondary analysis of clinical trials or retrospective analysis. Large randomized clinical trials (RCT) on this issue lack, and the effect of VLPD on renal death remain to be addressed. As well, information on patients' compliance to VLPD prescription and on the impact of VLPD on the quality of life are needed. Finally, also the effects of VLPD on both cardiovascular risk factors and mortality remain to be completely evaluated. The primary aim of this study is to evaluate, by mean of a RCT, the effect of the very low protein diet on the renal death in renal patients affected by chronic renal insufficiency of moderate to advanced degree (CKD stages 4 and 5). Secondary aims are to evaluate the effect of VLPD on cardiovascular risk factors, morbidity and mortality, the adherence to VLPD, and the relationship between VLPD and quality of life.

Official Title
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Effects of Very Low Protein Diet Supplemented With Ketoanalogs on Renal Death in Phase 4/5 Chronic Kidney Disease (CKD) - ERIKA Study

Conditions
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Chronic Renal Insufficiency

Intervention / Treatment
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* Behavioral: Very low protein diet
* Behavioral: Low protein diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with chronic renal insufficiency in stage CKD 4 and 5 (GFR < 30 ml/min/1.73m2, estimated by the 24-hours creatinine clearance) receiving conservative treatment for CKD Incident patients with chronic renal insufficiency in stage CKD 4 and 5 (GFR < 30 ml/min/1.73m2, estimated by the 24-hours creatinine clearance), provided stable renal function determined by two 24-hour measurements of creatinine clearance 2 weeks a part Exclusion Criteria: Patients already on very low protein diet Change of creatinine clearance > 30% within the last 3 months Severe undernutrition as indicated by : BMI < 20 kg/m2 in presence of serum albumin < 3.0 g/dl, or BMI < 17.5 kg/m2 whatever albumin value body weight reduction > 7.5% within the last 3 months Severe obesity as indicated by BMI > 35 kg/m2 Pregnancy or feeding Chronic treatment with steroid or cytotoxic drugs Fast progressing glomerulonephritis Active SLE and vasculitis Cardiac failure stage IV NYHA Advanced liver cirrhosis Active cancer diseases Severe encephalopathy associated with lack of spontaneous feeding Chronic obstructive respiratory diseases needing oxygen treatment

Ages Eligible for Study
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Minimum Age: 18 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: VLPD diet<br>Adavnced CKD patients (stage 4-5) on a very low protein diet | Behavioral: Very low protein diet<br>* 0.3 g of proteins per kilo of body weight per day, supplemented with a mixture of essential aminoacids and chetoacids<br>* Other names: VLPD;|
| Active Comparator: LPD diet<br>Adavnced CKD patients (stage 4-5) on a low protein diet | Behavioral: Low protein diet<br>* 0.6 g of protein per kilo of body weight per day<br>* Other names: LPD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to renal death, defined as the first event between start of renal replacement therapy or patient death |  | Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compliance to diet |  | Months | 
| Quality of life |  | Months | 
| Cardiovascular morbidity, defined by angina, heart failure, myocardial infarction, left ventricular mass, stroke, blood pressure, lipid profile, calcium/phosphorus/parathormone status and Charlson comorbidity index, at the start of dialysis |  | Months | 
| Nutritional status, defined by anthropo-plicometry, biochemistry, body bioimpedance analysis (BIA), subjective global nutritional assessment (SGA), at the start and during the 1st year of dialysis |  | Months | 
| Cardiovascular mortality |  | Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic renal insufficiency, CKD stage 4, CKD stage 5, Protein intake, Low protein diet, Very low protein diet, Ketoanalogs, Renal death