Tags

Type your tag names separated by a space and hit enter

Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade.
Am J Kidney Dis. 2015 Feb; 65(2):259-66.AJ

Abstract

BACKGROUND

Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patients. Previous studies linked high fibroblast growth factor 23 (FGF-23) levels with volume overload; others linked higher serum phosphate levels with impaired RAAS-blockade efficacy. We hypothesized that FGF-23 reduces the capacity of dietary sodium restriction to potentiate RAAS blockade, impairing the antiproteinuric effect.

STUDY DESIGN

Post hoc analysis of cohort data from a randomized crossover trial with two 6-week study periods comparing proteinuria after a regular-sodium diet with proteinuria after a low-sodium diet, both during background angiotensin-converting enzyme inhibition.

SETTING & PARTICIPANTS

47 nondiabetic patients with CKD with residual proteinuria (median protein excretion, 1.9 [IQR, 0.8-3.1] g/d; mean age, 50±13 [SD] years; creatinine clearance, 69 [IQR, 50-110] mL/min).

PREDICTOR

Plasma carboxy-terminal FGF-23 levels.

OUTCOMES

Difference in residual proteinuria at the end of the regular-sodium versus low-sodium study period. Residual proteinuria during the low-sodium diet period adjusted for proteinuria during the regular-sodium diet period.

RESULTS

Higher baseline FGF-23 level was associated with reduced antiproteinuric response to dietary sodium restriction (standardized β=-0.46; P=0.001; model R(2)=0.71). For every 100-RU/mL increase in FGF-23 level, the antiproteinuric response to dietary sodium restriction was reduced by 10.6%. Higher baseline FGF-23 level was a determinant of more residual proteinuria during the low-sodium diet (standardized β=0.27; P=0.003) in linear regression analysis adjusted for baseline proteinuria (model R(2)=0.71). There was no interaction with creatinine clearance (P interaction=0.5). Baseline FGF-23 level did not predict changes in systolic or diastolic blood pressure upon intensified antiproteinuric treatment.

LIMITATIONS

Observational study, limited sample size.

CONCLUSIONS

FGF-23 levels are associated independently with impaired antiproteinuric response to sodium restriction in addition to RAAS blockade. Future studies should address whether FGF-23-lowering strategies may further optimize proteinuria reduction by RAAS blockade combined with dietary sodium restriction.

Authors+Show Affiliations

Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.Department of Nephrology, VU Medical Center Amsterdam, Amsterdam, the Netherlands.Department of Nephrology, VU Medical Center Amsterdam, Amsterdam, the Netherlands.Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: m.h.de.borst@umcg.nl.No affiliation info available

Pub Type(s)

Journal Article
Observational Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25278093

Citation

Humalda, Jelmer K., et al. "Fibroblast Growth Factor 23 and the Antiproteinuric Response to Dietary Sodium Restriction During Renin-angiotensin-aldosterone System Blockade." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 65, no. 2, 2015, pp. 259-66.
Humalda JK, Lambers Heerspink HJ, Kwakernaak AJ, et al. Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade. Am J Kidney Dis. 2015;65(2):259-66.
Humalda, J. K., Lambers Heerspink, H. J., Kwakernaak, A. J., Slagman, M. C., Waanders, F., Vervloet, M. G., Ter Wee, P. M., Navis, G., & de Borst, M. H. (2015). Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 65(2), 259-66. https://doi.org/10.1053/j.ajkd.2014.07.022
Humalda JK, et al. Fibroblast Growth Factor 23 and the Antiproteinuric Response to Dietary Sodium Restriction During Renin-angiotensin-aldosterone System Blockade. Am J Kidney Dis. 2015;65(2):259-66. PubMed PMID: 25278093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade. AU - Humalda,Jelmer K, AU - Lambers Heerspink,Hiddo J, AU - Kwakernaak,Arjan J, AU - Slagman,Maartje C J, AU - Waanders,Femke, AU - Vervloet,Marc G, AU - Ter Wee,Pieter M, AU - Navis,Gerjan, AU - de Borst,Martin H, AU - ,, Y1 - 2014/09/30/ PY - 2014/01/11/received PY - 2014/07/28/accepted PY - 2014/10/4/entrez PY - 2014/10/4/pubmed PY - 2015/3/21/medline KW - Fibroblast growth factor 23 (FGF-23) KW - angiotensin receptor blocker (ARB) KW - angiotensin-converting enzyme (ACE) inhibitor KW - antiproteinuric KW - chronic kidney disease (CKD) KW - phosphaturic hormone KW - proteinuria KW - renin-angiotensin-aldosterone system (RAAS) blockade KW - sodium restriction KW - volume overload SP - 259 EP - 66 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 65 IS - 2 N2 - BACKGROUND: Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patients. Previous studies linked high fibroblast growth factor 23 (FGF-23) levels with volume overload; others linked higher serum phosphate levels with impaired RAAS-blockade efficacy. We hypothesized that FGF-23 reduces the capacity of dietary sodium restriction to potentiate RAAS blockade, impairing the antiproteinuric effect. STUDY DESIGN: Post hoc analysis of cohort data from a randomized crossover trial with two 6-week study periods comparing proteinuria after a regular-sodium diet with proteinuria after a low-sodium diet, both during background angiotensin-converting enzyme inhibition. SETTING & PARTICIPANTS: 47 nondiabetic patients with CKD with residual proteinuria (median protein excretion, 1.9 [IQR, 0.8-3.1] g/d; mean age, 50±13 [SD] years; creatinine clearance, 69 [IQR, 50-110] mL/min). PREDICTOR: Plasma carboxy-terminal FGF-23 levels. OUTCOMES: Difference in residual proteinuria at the end of the regular-sodium versus low-sodium study period. Residual proteinuria during the low-sodium diet period adjusted for proteinuria during the regular-sodium diet period. RESULTS: Higher baseline FGF-23 level was associated with reduced antiproteinuric response to dietary sodium restriction (standardized β=-0.46; P=0.001; model R(2)=0.71). For every 100-RU/mL increase in FGF-23 level, the antiproteinuric response to dietary sodium restriction was reduced by 10.6%. Higher baseline FGF-23 level was a determinant of more residual proteinuria during the low-sodium diet (standardized β=0.27; P=0.003) in linear regression analysis adjusted for baseline proteinuria (model R(2)=0.71). There was no interaction with creatinine clearance (P interaction=0.5). Baseline FGF-23 level did not predict changes in systolic or diastolic blood pressure upon intensified antiproteinuric treatment. LIMITATIONS: Observational study, limited sample size. CONCLUSIONS: FGF-23 levels are associated independently with impaired antiproteinuric response to sodium restriction in addition to RAAS blockade. Future studies should address whether FGF-23-lowering strategies may further optimize proteinuria reduction by RAAS blockade combined with dietary sodium restriction. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/25278093/Fibroblast_growth_factor_23_and_the_antiproteinuric_response_to_dietary_sodium_restriction_during_renin_angiotensin_aldosterone_system_blockade_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(14)01155-X DB - PRIME DP - Unbound Medicine ER -