The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease

Authors

Valentin Faerber, Department of Medical Scientific Affairs, Pharma and Nutrition, Fresenius Kabi Deutschland GmbH, 61352 Bad Homburg, Germany.
Katharina S. Kuhn, Department of Medical Scientific Affairs, Pharma and Nutrition, Fresenius Kabi Deutschland GmbH, 61352 Bad Homburg, Germany.
Liliana Garneata, "Dr. Carol Davila" Teaching Hospital of Nephrology, 4 Calea Grivitei, Sector 1, 010731 Bucharest, Romania.
Kamyar Kalantar-Zadeh, Division of Nephrology Hypertension and Kidney Transplantation, Department of Medicine, University of California Irvine (UCI), Orange, CA 90286, USA.
Sahir Kalim, Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Dominic S. Raj, Division of Kidney Diseases and Hypertension, George Washington University School of Medicine, Washington, DC 20037, USA.
Martin Westphal, Department of Medical Scientific Affairs, Pharma and Nutrition, Fresenius Kabi Deutschland GmbH, 61352 Bad Homburg, Germany.

Document Type

Journal Article

Publication Date

8-8-2023

Journal

Nutrients

Volume

15

Issue

16

DOI

10.3390/nu15163503

Keywords

carbamylation; chronic kidney disease; diet; dysbiosis; microbiome; posttranslational protein modification; protein restricted; urea; uremic toxin

Abstract

In chronic kidney disease (CKD), metabolic derangements resulting from the interplay between decreasing renal excretory capacity and impaired gut function contribute to accelerating disease progression and enhancing the risk of complications. To protect residual kidney function and improve quality of life in conservatively managed predialysis CKD patients, current guidelines recommend protein-restricted diets supplemented with essential amino acids (EAAs) and their ketoanalogues (KAs). In clinical studies, such an approach improved nitrogen balance and other secondary metabolic disturbances, translating to clinical benefits, mainly the delayed initiation of dialysis. There is also increasing evidence that a protein-restricted diet supplemented with KAs slows down disease progression. In the present review article, recent insights into the role of KA/EAA-supplemented protein-restricted diets in delaying CKD progression are summarized, and possible mechanistic underpinnings, such as protein carbamylation and gut dysbiosis, are elucidated. Emerging evidence suggests that lowering urea levels may reduce protein carbamylation, which might contribute to decreased morbidity and mortality. Protein restriction, alone or in combination with KA/EAA supplementation, modulates gut dysbiosis and decreases the generation of gut-derived uremic toxins associated, e.g., with cardiovascular disease, inflammation, protein energy wasting, and disease progression. Future studies are warranted to assess the effects on the gut microbiome, the generation of uremic toxins, as well as markers of carbamylation.

APA Citation

Faerber, Valentin; Kuhn, Katharina S.; Garneata, Liliana; Kalantar-Zadeh, Kamyar; Kalim, Sahir; Raj, Dominic S.; and Westphal, Martin, "The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease" (2023). GW Authored Works. Paper 3271.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3271

Department

Medicine