The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease
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 o...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Online Access: | https://www.mdpi.com/2072-6643/15/16/3503 |
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| author | Valentin Faerber Katharina S. Kuhn Liliana Garneata Kamyar Kalantar-Zadeh Sahir Kalim Dominic S. Raj Martin Westphal |
| author_facet | Valentin Faerber Katharina S. Kuhn Liliana Garneata Kamyar Kalantar-Zadeh Sahir Kalim Dominic S. Raj Martin Westphal |
| author_sort | Valentin Faerber |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T23:40:35Z |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T23:40:35Z |
| publishDate | 2023-08-01 |
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| series | Nutrients |
| spelling | doaj.art-6cdc9de3017343eaa29c7a5d542eaf6a2023-11-19T02:28:43ZengMDPI AGNutrients2072-66432023-08-011516350310.3390/nu15163503The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney DiseaseValentin Faerber0Katharina S. Kuhn1Liliana Garneata2Kamyar Kalantar-Zadeh3Sahir Kalim4Dominic S. Raj5Martin Westphal6Department of Medical Scientific Affairs, Pharma and Nutrition, Fresenius Kabi Deutschland GmbH, 61352 Bad Homburg, GermanyDepartment of Medical Scientific Affairs, Pharma and Nutrition, Fresenius Kabi Deutschland GmbH, 61352 Bad Homburg, Germany“Dr. Carol Davila” Teaching Hospital of Nephrology, 4 Calea Grivitei, Sector 1, 010731 Bucharest, RomaniaDivision of Nephrology Hypertension and Kidney Transplantation, Department of Medicine, University of California Irvine (UCI), Orange, CA 90286, USADivision of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USADivision of Kidney Diseases and Hypertension, George Washington University School of Medicine, Washington, DC 20037, USADepartment of Medical Scientific Affairs, Pharma and Nutrition, Fresenius Kabi Deutschland GmbH, 61352 Bad Homburg, GermanyIn 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.https://www.mdpi.com/2072-6643/15/16/3503chronic kidney diseasedietprotein restrictedmicrobiomedysbiosisuremic toxin |
| spellingShingle | Valentin Faerber Katharina S. Kuhn Liliana Garneata Kamyar Kalantar-Zadeh Sahir Kalim Dominic S. Raj Martin Westphal The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease Nutrients chronic kidney disease diet protein restricted microbiome dysbiosis uremic toxin |
| title | The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease |
| title_full | The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease |
| title_fullStr | The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease |
| title_full_unstemmed | The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease |
| title_short | The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease |
| title_sort | microbiome and protein carbamylation potential targets for protein restricted diets supplemented with ketoanalogues in predialysis chronic kidney disease |
| topic | chronic kidney disease diet protein restricted microbiome dysbiosis uremic toxin |
| url | https://www.mdpi.com/2072-6643/15/16/3503 |
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