Effect of Protein Restriction Plus EAA/KA Supplementation on GFR Decline in CKD

Does Protein Restriction Plus Essential Amino Acids and Keto-analogues Supplementation Have a Beneficial Effect on GFR Decline in CKD Patients?

This study aims to investigate the effect of protein restriction plus KA/EAA supplementation on GFR decline in CKD patients.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Other: low protein diet; Drug: essential amino acids and keto-analogues supplementation

Detailed Description

In chronic kidney disease (CKD) patients, ketoacid analogues of essential amino acids (KA/EAA) are administered to reduce the production of harmful metabolic products and enhance nutritional status. Protein restriction combined with AA supplement may have beneficial effects on CKD in several ways, by reducing nitrogen waste, oxidative stress, and inflammation, and by protecting against hemodynamic changes in glomerular hyperfiltration.

several clinical trials have documented that very low protein diets (VLPD) supplemented with KA/EAA preserve the rate of progression of advanced CKD. However, in long-term follow-up of the MDRD study, VLPD plus KA/EAA treatment did not delay progression to dialysis or transplantation.

As a result, no firm conclusions have been drawn on the effectiveness of protein-restricted diets combined with KA/EAA supplements in retarding CKD progression.

• Study Type: Observational
• Enrollment (Actual): 400

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21526
    • Faculty of Medicine, Aexandria University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

medical records of Patients with CKD stages (G2 to G4), will be retrospectively screened from December 2021 till December 2023.

Patients will be divided into two groups:

Control group who was on low protein diet only, while the other group (interventional) consumed KA/EAA plus very low protein diet.

Description

Inclusion Criteria:

• Patients with CKD stages (G2 to G4), aged ≥ 18 years old

Exclusion Criteria:

1. Active malignancy
2. Protein energy wasting
3. Advanced organ disease
4. pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control group; include patients who were on low protein diet only	Other: low protein diet; patients were on low protein diet only
interventional group; include patients who consumed KA/EAA plus very low protein diet	Drug: essential amino acids and keto-analogues supplementation; very low protein diet plus essential amino acids and keto-analogues supplementation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GFR decline	effect on GFR change at one year from baseline in CKD patients	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect on albumin	measurement of albumin change at one year from baseline	24 months
effect on calcium	measurement of calcium change at one year from baseline	24 months

Collaborators and Investigators

• Sponsor: Alexandria University
• Investigators: Principal Investigator: Mohamed Mamdouh Elsayed, MD, lecturer; Study Chair: Bassant Sabry, Pharmacist; Study Chair: Alaa Soliman, Pharmacist; Study Chair: Mohamed A. Mekawy, Pharmacist; Study Chair: Engy Emam, Clinical Pharmacist

Publications and helpful links

General Publications

• Feiten SF, Draibe SA, Watanabe R, Duenhas MR, Baxmann AC, Nerbass FB, Cuppari L. Short-term effects of a very-low-protein diet supplemented with ketoacids in nondialyzed chronic kidney disease patients. Eur J Clin Nutr. 2005 Jan;59(1):129-36. doi: 10.1038/sj.ejcn.1602050.
• Gao X, Huang L, Grosjean F, Esposito V, Wu J, Fu L, Hu H, Tan J, He C, Gray S, Jain MK, Zheng F, Mei C. Low-protein diet supplemented with ketoacids reduces the severity of renal disease in 5/6 nephrectomized rats: a role for KLF15. Kidney Int. 2011 May;79(9):987-96. doi: 10.1038/ki.2010.539. Epub 2011 Jan 19.
• Jiang Z, Zhang X, Yang L, Li Z, Qin W. Effect of restricted protein diet supplemented with keto analogues in chronic kidney disease: a systematic review and meta-analysis. Int Urol Nephrol. 2016 Mar;48(3):409-18. doi: 10.1007/s11255-015-1170-2. Epub 2015 Nov 30.
• Menon V, Kopple JD, Wang X, Beck GJ, Collins AJ, Kusek JW, Greene T, Levey AS, Sarnak MJ. Effect of a very low-protein diet on outcomes: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am J Kidney Dis. 2009 Feb;53(2):208-17. doi: 10.1053/j.ajkd.2008.08.009. Epub 2008 Oct 31.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Actual): March 30, 2024
• Study Completion (Actual): May 15, 2024

Study Registration Dates

• First Submitted: July 1, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 19, 2023

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 16, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: CKD; ketoanalogues; GFR; essential amino acids; protein restriction
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: effect of EAA/KA on GFR in CKD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No