The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease
Several factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats we...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/13/7/503 |
| _version_ | 1797526003531120640 |
|---|---|
| author | Irene Faria Duayer Eduardo Jorge Duque Clarice Kazue Fujihara Ivone Braga de Oliveira Luciene Machado dos Reis Flavia Gomes Machado Fabiana Giorgetti Graciolli Vanda Jorgetti Roberto Zatz Rosilene Motta Elias Rosa Maria Affonso Moysés |
| author_facet | Irene Faria Duayer Eduardo Jorge Duque Clarice Kazue Fujihara Ivone Braga de Oliveira Luciene Machado dos Reis Flavia Gomes Machado Fabiana Giorgetti Graciolli Vanda Jorgetti Roberto Zatz Rosilene Motta Elias Rosa Maria Affonso Moysés |
| author_sort | Irene Faria Duayer |
| collection | DOAJ |
| description | Several factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%; high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of α-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to the HiP group. Our findings highlight the action of phosphate in the induction of kidney interstitial inflammation and fibrosis, contributing to the progression of renal disease. A possible effect of phosphate on the dysregulation of the renal cell autophagy mechanism needs further investigation with clinical studies. |
| first_indexed | 2024-03-10T09:21:05Z |
| format | Article |
| id | doaj.art-bbca046eb6a5476cafd5092e821e53c3 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T09:21:05Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-bbca046eb6a5476cafd5092e821e53c32023-11-22T05:11:16ZengMDPI AGToxins2072-66512021-07-0113750310.3390/toxins13070503The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney DiseaseIrene Faria Duayer0Eduardo Jorge Duque1Clarice Kazue Fujihara2Ivone Braga de Oliveira3Luciene Machado dos Reis4Flavia Gomes Machado5Fabiana Giorgetti Graciolli6Vanda Jorgetti7Roberto Zatz8Rosilene Motta Elias9Rosa Maria Affonso Moysés10LIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilLIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, BrazilSeveral factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%; high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of α-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to the HiP group. Our findings highlight the action of phosphate in the induction of kidney interstitial inflammation and fibrosis, contributing to the progression of renal disease. A possible effect of phosphate on the dysregulation of the renal cell autophagy mechanism needs further investigation with clinical studies.https://www.mdpi.com/2072-6651/13/7/503phosphatedietCKD progressionrenal fibrosisautophagyapoptosis |
| spellingShingle | Irene Faria Duayer Eduardo Jorge Duque Clarice Kazue Fujihara Ivone Braga de Oliveira Luciene Machado dos Reis Flavia Gomes Machado Fabiana Giorgetti Graciolli Vanda Jorgetti Roberto Zatz Rosilene Motta Elias Rosa Maria Affonso Moysés The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease Toxins phosphate diet CKD progression renal fibrosis autophagy apoptosis |
| title | The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease |
| title_full | The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease |
| title_fullStr | The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease |
| title_full_unstemmed | The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease |
| title_short | The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease |
| title_sort | protein independent role of phosphate in the progression of chronic kidney disease |
| topic | phosphate diet CKD progression renal fibrosis autophagy apoptosis |
| url | https://www.mdpi.com/2072-6651/13/7/503 |
| work_keys_str_mv | AT irenefariaduayer theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT eduardojorgeduque theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT claricekazuefujihara theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT ivonebragadeoliveira theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT lucienemachadodosreis theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT flaviagomesmachado theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT fabianagiorgettigraciolli theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT vandajorgetti theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT robertozatz theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT rosilenemottaelias theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT rosamariaaffonsomoyses theproteinindependentroleofphosphateintheprogressionofchronickidneydisease AT irenefariaduayer proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT eduardojorgeduque proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT claricekazuefujihara proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT ivonebragadeoliveira proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT lucienemachadodosreis proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT flaviagomesmachado proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT fabianagiorgettigraciolli proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT vandajorgetti proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT robertozatz proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT rosilenemottaelias proteinindependentroleofphosphateintheprogressionofchronickidneydisease AT rosamariaaffonsomoyses proteinindependentroleofphosphateintheprogressionofchronickidneydisease |