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

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

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).

Study Overview

• Status: Unknown
• Conditions: Chronic Renal Insufficiency
• Intervention / Treatment: Behavioral: Very low protein diet; Behavioral: Low protein diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Castellammare di Stabia, Italy, 80053
    • Nephrology Unit, Castellammare Hospital
  • Napoli, Italy, 80123
    • Nephrology Division, Medical School, University "Federico II" of Naples
  • Napoli, Italy, 80138
    • Nephrology Division, Medical School, Second University of Naples
  • AV
    • Avellino, AV, Italy, 83100
      • Nephrology Unit, "Moscati" Hospital
    • Sant' Angelo dei Lombardi, AV, Italy, 83054
      • Nephrology Unit, S. Angelo dei Lombardi Hospital
    • Solofra, AV, Italy, 83029
      • Nephrology Unit "A. Landolfi" Hospital
  • BA
    • Bari, BA, Italy, 70100
      • Nephrology Division, Medical School, University of Bari
  • BR
    • Brindisi, BR, Italy, 72100
      • Nephrology Unit, Brindisi Hospital
  • CE
    • Piedimonte Matese, CE, Italy, 81016
      • Nephrology Unit, Piedimonte Matese Hospital
    • San Felice a Cancello, CE, Italy, 81027
      • Nephrology Unit, S. Felice a Cancello Hospital
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Nephrology Division, Medical School, University of Catanzaro
  • FG
    • Foggia, FG, Italy, 71100
      • Nephrology Division, Medical School, University of Foggia
    • Foggia, FG, Italy, 71100
      • Nephrology Unit, Foggia Hospital
    • San Severo, FG, Italy, 71016
      • Nephrology Unit, San Severo Hospital
  • LE
    • Galatina, LE, Italy, 73013
      • Nephrology Unit, Galatina Hospital
  • PZ
    • Potenza, PZ, Italy, 85100
      • Nephrology Division, "San Carlo" Hospital
  • SA
    • Polla, SA, Italy, 84035
      • Nephrology Unit, "Curto" Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 :

  1. BMI < 20 kg/m2 in presence of serum albumin < 3.0 g/dl, or BMI < 17.5 kg/m2 whatever albumin value
  2. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VLPD diet; Adavnced CKD patients (stage 4-5) on a very low protein diet	Behavioral: Very low protein diet; 0.3 g of proteins per kilo of body weight per day, supplemented with a mixture of essential aminoacids and chetoacids; Other Names: VLPD
Active Comparator: LPD diet; Adavnced CKD patients (stage 4-5) on a low protein diet	Behavioral: Low protein diet; 0.6 g of protein per kilo of body weight per day; Other Names: LPD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Azienda Sanitaria ASL Avellino 2
• Investigators: Study Chair: Vincenzo Bellizzi, MD, PhD, Nephrology Unit "A. Landolfi" Hospital, Solofra (AV) Italy; Study Chair: Giuseppe Conte, MD, Division of Nephrology, Medical School, Second University of Naples, Naples, Italy; Study Chair: Ciro Gallo, MD, Biostatistics Unit, Medical School, Second University of Naples, Naples, Italy

Publications and helpful links

General Publications

• Di Iorio BR, Minutolo R, De Nicola L, Bellizzi V, Catapano F, Iodice C, Rubino R, Conte G. Supplemented very low protein diet ameliorates responsiveness to erythropoietin in chronic renal failure. Kidney Int. 2003 Nov;64(5):1822-8. doi: 10.1046/j.1523-1755.2003.00282.x.
• Di Iorio BR, Bellizzi V, Minutolo R, De Nicola L, Iodice C, Conte G. Supplemented very low-protein diet in advanced CRF: is it money saving? Kidney Int. 2004 Feb;65(2):742. doi: 10.1111/j.1523-1755.2004.404_2.x. No abstract available.
• Bellizzi V, Di Iorio BR, De Nicola L, Minutolo R, Zamboli P, Trucillo P, Catapano F, Cristofano C, Scalfi L, Conte G; ERIKA Study-group. Very low protein diet supplemented with ketoanalogs improves blood pressure control in chronic kidney disease. Kidney Int. 2007 Feb;71(3):245-51. doi: 10.1038/sj.ki.5001955. Epub 2006 Oct 11.
• Hahn D, Hodson EM, Fouque D. Low protein diets for non-diabetic adults with chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 29;10(10):CD001892. doi: 10.1002/14651858.CD001892.pub5.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Anticipated): July 1, 2011
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: May 5, 2006
• First Submitted That Met QC Criteria: May 5, 2006
• First Posted (Estimate): May 9, 2006

Study Record Updates

• Last Update Posted (Estimate): June 27, 2011
• Last Update Submitted That Met QC Criteria: June 23, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Low protein diet; Chronic renal insufficiency; Protein intake; CKD stage 4; CKD stage 5; Very low protein diet; Ketoanalogs; Renal death
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: KA1-1425