SEARCHNARRATIVE_REVIEWnephrology, nutrition

narrative_review·nephrology, nutrition, preclinical research, biomedical research·PMC10459041

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

Nutrients · 7 authors, 5 centres

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TL;DR

This narrative review summarizes evidence that protein-restricted diets supplemented with ketoanalogues and essential amino acids may modulate the gut microbiome and reduce uremic toxin production in predialysis CKD patients. It also highlights protein carbamylation as an emerging biomarker and mechanistic target linked to CKD progression and cardiovascular risk.

Full summary

352 CHARS

The review describes how gut dysbiosis contributes to the accumulation of uremic toxins and CKD progression, and summarizes evidence from clinical studies—including one randomized controlled trial—indicating that protein-restricted diets can modulate gut microbiota composition, restore intestinal barrier integrity, and reduce uremic toxin generation.

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narrative_review

SPECIALTY

nephrology

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AI pipeline

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ORIGINAL PAPER

PMC10459041

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

Nutrients

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ABSTRACT

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. Keywords: chronic kidney disease, diet, protein restricted, microbiome, dysbiosis, uremic toxin, urea, carbamylation, posttranslational protein modification

CITATION EXPORT

Valentin Faerber, Katharina S Kuhn, Liliana Garneata et al.. The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease. Nutrients. (2023). https://doi.org/10.3390/nu15163503

AUTHORS

7 · 5 CENTRES

Valentin Faerber, Katharina S Kuhn, Liliana Garneata, Kamyar Kalantar-Zadeh, Sahir Kalim, Dominic S Raj, Martin Westphal

1Department of Medical Scientific Affairs, Pharma and Nutrition, Fresenius Kabi Deutschland GmbH, 61352 Bad Homburg, Germany; [email protected] (K.S.K.); [email protected] (M.W.)
2“Dr. Carol Davila” Teaching Hospital of Nephrology, 4 Calea Grivitei, Sector 1, 010731 Bucharest, Romania; [email protected]
3Division of Nephrology Hypertension and Kidney Transplantation, Department of Medicine, University of California Irvine (UCI), Orange, CA 90286, USA; [email protected]
4Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; [email protected]
5Division of Kidney Diseases and Hypertension, George Washington University School of Medicine, Washington, DC 20037, USA; [email protected]