Clinical trial NCT00323713: Very Low Protein Diet and Renal Death in Chronic Kidney Disease (CKD)-ERIKA Study
Official title: Effects of Very Low Protein Diet Supplemented With Ketoanalogs on Renal Death in Phase 4/5 Chronic Kidney Disease (CKD) - ERIKA Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Renal Insufficiency
Keywords: Chronic renal insufficiency
CKD stage 4
CKD stage 5
Protein intake
Low protein diet
Very low protein diet
Ketoanalogs
Renal death
Lead sponsor: Azienda Sanitaria ASL Avellino 2
Sponsor class: OTHER
First posted: 2006-05-09
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to renal death, defined as the first event between start of renal replacement therapy or patient death
timeFrame: Months
Secondary outcomes:
measure: Compliance to diet
timeFrame: Months
measure: Quality of life
timeFrame: Months
measure: 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
timeFrame: Months
measure: 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
timeFrame: Months
measure: Cardiovascular mortality
timeFrame: Months
Other outcomes:
Locations:
city: Avellino
country: Italy
facility: Nephrology Unit, "Moscati" Hospital
state: AV
city: Sant' Angelo dei Lombardi
country: Italy
facility: Nephrology Unit, S. Angelo dei Lombardi Hospital
state: AV
city: Solofra
country: Italy
facility: Nephrology Unit "A. Landolfi" Hospital
state: AV
city: Bari
country: Italy
facility: Nephrology Division, Medical School, University of Bari
state: BA
city: Brindisi
country: Italy
facility: Nephrology Unit, Brindisi Hospital
state: BR
city: Piedimonte Matese
country: Italy
facility: Nephrology Unit, Piedimonte Matese Hospital
state: CE
city: San Felice a Cancello
country: Italy
facility: Nephrology Unit, S. Felice a Cancello Hospital
state: CE
city: Catanzaro
country: Italy
facility: Nephrology Division, Medical School, University of Catanzaro
state: CZ
city: Foggia
country: Italy
facility: Nephrology Division, Medical School, University of Foggia
state: FG
city: Foggia
country: Italy
facility: Nephrology Unit, Foggia Hospital
state: FG
city: San Severo
country: Italy
facility: Nephrology Unit, San Severo Hospital
state: FG
city: Galatina
country: Italy
facility: Nephrology Unit, Galatina Hospital
state: LE
city: Potenza
country: Italy
facility: Nephrology Division, "San Carlo" Hospital
state: PZ
city: Polla
country: Italy
facility: Nephrology Unit, "Curto" Hospital
state: SA
city: Castellammare di Stabia
country: Italy
facility: Nephrology Unit, Castellammare Hospital
city: Napoli
country: Italy
facility: Nephrology Division, Medical School, University "Federico II" of Naples
city: Napoli
country: Italy
facility: Nephrology Division, Medical School, Second University of Naples
Study officials:
affiliation: Nephrology Unit "A. Landolfi" Hospital, Solofra (AV) Italy
name: Vincenzo Bellizzi, MD, PhD
role: STUDY_CHAIR
affiliation: Division of Nephrology, Medical School, Second University of Naples, Naples, Italy
name: Giuseppe Conte, MD
role: STUDY_CHAIR
affiliation: Biostatistics Unit, Medical School, Second University of Naples, Naples, Italy
name: Ciro Gallo, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.