Low Protein Diet in CKD Patients at Risk of Malnutrition

Study Overview
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Brief Summary
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It's a pilot study with an open label randomized-controlled design. Estimated number of patients should have been 38, taking in account of a maximal drop out up to 20% of the sample. We enrolled 35 patients, 27 of whom terminated the study as per protocol (14 in the Low protein (LP) group and 13 in the Normo Protein (NP) group). Patients were treated for six months with two different dietary prescriptions: LP group (n=17) was prescribed high calories/low proteins diet (30 Kcal/kg and 0.6-0.7gr/kg respectively). In order to assure prescribed calorie intake, this group was supplemented with commercial protein free products (protein content <2%). NP group (n=18) was prescribed high calories/normal proteins diet (30 kcal/kg and 0.8 gr/kg respectively). The primary hypothesis of the study was that in CKD patients at risk of malnutrition (4 ≤ MIS ≥7) with a persistent spontaneous low protein and calories intake, the prescription of a LP diet was not inferior to NP diet regarding the development of malnutrition (i.e.MIS ≥ 8). We also wanted to test whether in these patients, the prescription of a LP diet was superior to the NP comparator regarding the control of the metabolic complication of chronic kidney diseases (i.e hyperphosphatemia, inflammation and metabolic acidosis), the progression on dyna/sarcopenia, inflammation and possibly on the progression of renal disease itself.

Detailed Description
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Nutritional status will be evaluated through: Malnutrition Inflammation Score (MIS), Anthropometric measurements, albumin, prealbumin, transferrin, 24h urinary nitrogen, bioimpedance analysis (BIA), periodic 24h dietary diaries, International Society of Renal Nutrition and Metabolism (ISRNM), Physical performance will be evaluated through: Short Physical Performance Battery (SPPB) Handgrip strength Inflammation assessment: c-reactive protein (CRP) Interleukine-6 (IL6) whole blood Neutrophil/lymphocyte ratio Renal function assessment: eGFR based on serum creatinine and cystatin C average creatinine and urea clearance Uremic metabolic alteration: serum urea serum phosphate serum FGF23 parathormone (PTH), plasma pH and bicarbonate Time points of evaluation Dietary compliance has been assessed by a trained nutritionist at months 1, 2, 3 and 6. Dietary consumption was estimated by using dietary diaries and normalized catabolic protein rate (nPCR) measurement at baseline, 3 and at 6 months. Nutritional status and physical performance have been evaluated monthly for the first three months and then at 6 months.

Official Title
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Is There Any Indication for Protein Free Products in Patients With Advanced CKD at Risk of Malnutrition?A Pilot Randomized Controlled Trial

Conditions
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Chronic Kidney Diseases, Malnutrition

Intervention / Treatment
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* Dietary Supplement: LP group
* Other: NP group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: advanced CKD not yet on renal replacement therapy (10< - eGFRcreat <30 ml/min) age >65 years at risk of malnutrition at Malnutrition Inflammation Score (4≤MIS≤7) spontaneous low protein-energy intake (proteins < 0.8g/kg and energy < 25 kcal/kg). Exclusion Criteria: Active chronic infectious diseases Heart failure of severity > NYHA2 Active neoplastic diseases Inability to cooperate Presumed overall life expectancy < 6 month Decompensated liver diseases Malabsorption Decompensated thyroid o surrenal diseases Refusal to participate Immunosuppressive and/or steroid therapy

Ages Eligible for Study
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Minimum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants were treated for six months with two different dietary prescriptions: LP group (n=17) was prescribed high calories/low proteins diet (30 Kcal/kg and 0.6-0.7gr/kg respectively). In order to assure prescribed calorie intake, this group was supplemented with commercial protein free products (protein content <2%). NP group (n=18) was prescribed high calories/normal proteins diet (30 kcal/kg and 0.8 gr/kg respectively).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LP group<br>LP group (n=17) was prescribed high calories/low proteins diet (30 Kcal/kg and 0.6-0.7gr/kg respectively) supplemented with commercial protein free products (protein content <2%). | Dietary Supplement: LP group<br>* LP group patients replaced pasta, bread, biscuits etc. with low protein substitutes. We allowed them to consume more animal products than NP, preferring white meat to red meat and trying to limit cold cuts as much as possible. Furthermore, they were advised to prefer fresh or frozen fish, instead of dried or smoked one as well as to prefer fresh cheeses to seasoned ones. As for legumes, we advised to combine them with bread or normal cereals, for protein complementarity.<br>|
| Active Comparator: NP group<br>NP group (n=18) was prescribed high calories/normal proteins diet (30 kcal/kg and 0.8 gr/kg respectively) | Other: NP group<br>* NP group was given the indication to try to eat the second dish only once a day or to split the portion of the second plate between lunch and dinner, if they wanted to keep the habit of making the meal complete. It was also given the indication to prefer, among protein sources, those of plant origin. We also indicated to alternate or replace cow's milk with plant substitutes such as: rice, almonds' or oats' drinks. Furthermore, we suggested to prefer white meat and to avoid offal and processed meat. Moreover, we indicated to substitute dried or smoked fish with fresh or frozen one.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline MIS at 6th month | Malnutrition-inflammation score is a validated scoring system for the assessment of malnutrition and inflammation syndrome in patients with CKD. MIS involves the evaluation of ten different domains, each of which is categorized with 4 severity levels (score scale 0-3). A total score of 4-7 was considered indicative of mild malnutrition and a score ≥8 of severe malnourishment | measured at baseline and 6 months. | 
| Change from baseline serum albumin at 6th month | in g/dL | measured at baseline and at 6 months. | 
| intergroup MIS comparison at 6 months | Malnutrition-inflammation score is a validated scoring system for the assessment of malnutrition and inflammation syndrome in patients with CKD. MIS involves the evaluation of ten different domains, each of which is categorized with 4 severity levels (score scale 0-3). A total score of 4-7 was considered indicative of mild malnutrition and a score ≥8 of severe malnourishment | 6th month | 
| Intergroup comparison of the number of patients that reached a MIS ≥8 at 6 months | Malnutrition-inflammation score is a validated scoring system for the assessment of malnutrition and inflammation syndrome in patients with CKD. MIS involves the evaluation of ten different domains, each of which is categorized with 4 severity levels (score scale 0-3). A total score of 4-7 was considered indicative of mild malnutrition and a score ≥8 of severe malnourishment | 6th month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences of GFR estimated with creatinine | In ml/min/1,73m^2 | measured at baseline and at 6 months. | 
| Differences of GFR estimated with cystatin C | in ml/min/1,73m^2 | measured at baseline and at 6 months. | 
| Differences in serum urea | in mg/dl | measured at baseline and at 6 months. | 
| Differences in creatinine clarance | in ml/min | measured at baseline and at 6 months. | 
| Differences in phosphorous | in mg/dl | measured at baseline and at 6 months. | 
| Differences in FGF23 intact | in pg/mL | measured at baseline and at 6 months. | 
| Differences in FGF23 c-terminal | in RU/mL | measured at baseline and at 6 months. | 
| Differences in urinary phosphorous | in mg/24h | measured at baseline and at 6 months. | 
| Differences in PTH | in ng/L | measured at baseline and at 6 months. | 
| Differences in bicarbonate | in mEq/L | measured at baseline and at 6 months. | 
| Differences in pH | pH | measured at baseline and at 6 months. | 
| Differences in CRP | in mg/dl | measured at baseline and at 6 months. | 
| Differences in IL6 | in pg/mL | measured at baseline and at 6 months. | 
| Differences in the short physical performance battery scores | SPPB includes: test of standing balance, 4-meter walk and time to rise from a chair five times. Each SPPB component test is scored from 0 to 4. Higher scores indicate better physical performance | at months 1 and 6 | 
| Differences of the handgrip strength | in Kg. Handgrip strength was measured with Jamar dynamometer and was considered to be impaired for values <16kg in females and <27kg in males | measured at baseline and at 6 months. | 
| Differences in the body composition (lean body mass, fat body mass, water) in the two study groups (bio impedance) | water in L, Lean body mass in Kg/m2 and fat body mass in Kg/m2. Body composition was measured by using a multifrequency bioelectrical impedance analysis device (BCM- Body Composition Monitor, Fresenius Medical Care, Bad Homburg, Germany). | measured at baseline and at 6 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic kidney disease, Malnutrition