TY - JOUR
T1 - Sodium restriction on top of renin-angiotensin-aldosterone system blockade increases circulating levels of N-acetyl-seryl-aspartyl-lysyl-proline in chronic kidney disease patients
AU - Kwakernaak, Arjan J.
AU - Waanders, Femke
AU - Slagman, Maartje C.J.
AU - Dokter, Martin M.
AU - Laverman, Gozewijn D.
AU - De Boer, Rudolf A.
AU - Navis, Gerjan
PY - 2013/12
Y1 - 2013/12
N2 - OBJECTIVE: Sodium restriction potentiates the efficacy of the rennin-angiotensin-aldosterone system (RAAS)-blockade and improves long-term cardiovascular and renal protection, even independent of the better blood pressure control. The mechanisms underlying the potentiation of cardiorenal protection by sodium restriction are incompletely understood. RAAS-blockade with angiotensin-converting enzyme (ACE) inhibitors increases circulating levels of the anti-inflammatory and antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl- proline (AcSDKP), which is assumed to contribute to its therapeutic effects. We hypothesized that sodium restriction on top of RAAS-blockade further increases AcSDKP, as a possible explanation for the enhanced effects of RAAS-blockade during sodium restriction.METHODS: To test this hypothesis, we performed a secondary analysis of a randomized clinical trial investigating 46 nondiabetic chronic kidney disease (CKD) patients (age 50 ± 13 years, 80% men) with overt proteinuria and mild to moderate renal insufficiency. Patients were subjected, in a crossover design, to four double-blind 6-week study periods with either regular sodium diet (194 ± 49 mmol Naday) or low sodium diet (102 ± 52 mmol Na/day) on top of either lisinopril (40 mg/day; single RAAS-blockade) or lisinopril plus valsartan (320 mg/day; dual RAAS-blockade).RESULTS:: Sodium restriction significantly increased circulating levels of AcSDKP during single and dual RAAS-blockade (P = 0.032 and 0.042, respectively). Linear mixed-model analysis confirmed that AcSDKP levels were increased in response to sodium restriction, irrespective of sex, age, creatinine clearance, blood pressure, BMI, single or dual RAAS-blockade, treatment sequence and other dietary factors, that is calcium and protein (P = 0.020).CONCLUSION: In patients with nondiabetic CKD, we demonstrated that sodium restriction, on top of single and dual RAAS-blockade, increases circulating levels of the anti-inflammatory and antifibrotic peptide AcSDKP. The rise in AcSDKP may contribute to the increased protection of RAAS-blockade during sodium restriction.
AB - OBJECTIVE: Sodium restriction potentiates the efficacy of the rennin-angiotensin-aldosterone system (RAAS)-blockade and improves long-term cardiovascular and renal protection, even independent of the better blood pressure control. The mechanisms underlying the potentiation of cardiorenal protection by sodium restriction are incompletely understood. RAAS-blockade with angiotensin-converting enzyme (ACE) inhibitors increases circulating levels of the anti-inflammatory and antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl- proline (AcSDKP), which is assumed to contribute to its therapeutic effects. We hypothesized that sodium restriction on top of RAAS-blockade further increases AcSDKP, as a possible explanation for the enhanced effects of RAAS-blockade during sodium restriction.METHODS: To test this hypothesis, we performed a secondary analysis of a randomized clinical trial investigating 46 nondiabetic chronic kidney disease (CKD) patients (age 50 ± 13 years, 80% men) with overt proteinuria and mild to moderate renal insufficiency. Patients were subjected, in a crossover design, to four double-blind 6-week study periods with either regular sodium diet (194 ± 49 mmol Naday) or low sodium diet (102 ± 52 mmol Na/day) on top of either lisinopril (40 mg/day; single RAAS-blockade) or lisinopril plus valsartan (320 mg/day; dual RAAS-blockade).RESULTS:: Sodium restriction significantly increased circulating levels of AcSDKP during single and dual RAAS-blockade (P = 0.032 and 0.042, respectively). Linear mixed-model analysis confirmed that AcSDKP levels were increased in response to sodium restriction, irrespective of sex, age, creatinine clearance, blood pressure, BMI, single or dual RAAS-blockade, treatment sequence and other dietary factors, that is calcium and protein (P = 0.020).CONCLUSION: In patients with nondiabetic CKD, we demonstrated that sodium restriction, on top of single and dual RAAS-blockade, increases circulating levels of the anti-inflammatory and antifibrotic peptide AcSDKP. The rise in AcSDKP may contribute to the increased protection of RAAS-blockade during sodium restriction.
KW - n/a OA procedure
KW - Fibrosis
KW - Inflammation
KW - N-acetyl-seryl-aspartyl-lysyl- proline
KW - Renoprotection
KW - Sodium restriction
KW - Chronic kidney disease (CKD)
UR - http://www.scopus.com/inward/record.url?scp=84888138002&partnerID=8YFLogxK
U2 - 10.1097/HJH.0b013e328364f5de
DO - 10.1097/HJH.0b013e328364f5de
M3 - Article
C2 - 24029871
SN - 0263-6352
VL - 31
SP - 2425
EP - 2432
JO - Journal of hypertension
JF - Journal of hypertension
IS - 12
ER -
