Abstract
Omega-3 poly-unsaturated fatty acids and mineral metabolism: novel therapy for cardiovascular disease in renal patients?
Deregulations in mineral metabolism, particularly related to phosphate and its regulating hormone fibroblast growth factor 23 (FGF23), are common in patients with chronic kidney disease (CKD) and renal transplant recipients. We demonstrated that in patients after kidney transplantation, a higher circulating level of FGF23 predisposes to an increased risk of cardiovascular mortality, independent of renal function and classical cardiovascular risk factors. This is in line with previous results from non-transplanted CKD patients, and underlines the potential role of this phosphate-regulating hormone in the development of cardiovascular disease.
We subsequently aimed to identify modifiable risk factors determining FGF23 levels. Using detailed information from dietary questionnaires and 24-hour urine collections, our studies revealed that the intake of fish and N-3 poly-unsaturated fatty acids (PUFAs) are inversely associated with circulating FGF23 levels. A lowering effect on FGF23 levels could at least partly explain the previously reported protection against cardiovascular disease by PUFAs. In a mouse model of renal inflammation we found that PUFA supplementation restored mineral metabolism and reduced inflammatory kidney damage and renal scarring. Finally, we studied FGF23 in participants of the Alpha Omega trial, a large randomized controlled trial testing the effects of PUFA supplementation in patients after myocardial infarction. We found small effects on FGF23 which did not reach statistical significance, possibly due to a relatively low PUFA dose in this trial. Yet, our findings identify PUFA supplementation as a potentially relevant strategy to improve cardiovascular outcomes in CKD patients, by an effect on phosphate metabolism.
Deregulations in mineral metabolism, particularly related to phosphate and its regulating hormone fibroblast growth factor 23 (FGF23), are common in patients with chronic kidney disease (CKD) and renal transplant recipients. We demonstrated that in patients after kidney transplantation, a higher circulating level of FGF23 predisposes to an increased risk of cardiovascular mortality, independent of renal function and classical cardiovascular risk factors. This is in line with previous results from non-transplanted CKD patients, and underlines the potential role of this phosphate-regulating hormone in the development of cardiovascular disease.
We subsequently aimed to identify modifiable risk factors determining FGF23 levels. Using detailed information from dietary questionnaires and 24-hour urine collections, our studies revealed that the intake of fish and N-3 poly-unsaturated fatty acids (PUFAs) are inversely associated with circulating FGF23 levels. A lowering effect on FGF23 levels could at least partly explain the previously reported protection against cardiovascular disease by PUFAs. In a mouse model of renal inflammation we found that PUFA supplementation restored mineral metabolism and reduced inflammatory kidney damage and renal scarring. Finally, we studied FGF23 in participants of the Alpha Omega trial, a large randomized controlled trial testing the effects of PUFA supplementation in patients after myocardial infarction. We found small effects on FGF23 which did not reach statistical significance, possibly due to a relatively low PUFA dose in this trial. Yet, our findings identify PUFA supplementation as a potentially relevant strategy to improve cardiovascular outcomes in CKD patients, by an effect on phosphate metabolism.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 14-Oct-2015 |
| Place of Publication | [Groningen] |
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| Print ISBNs | 978-90-367-7970-8 |
| Electronic ISBNs | 978-90-367-7969-2 |
| Publication status | Published - 2015 |