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Published in: Journal of Nephrology 1/2015

01-02-2015 | Original Article

Effects of phosphorus-restricted diet and phosphate-binding therapy on outcomes in patients with chronic kidney disease

Authors: Domenico Russo, Antonio Bellasi, Andrea Pota, Luigi Russo, Biagio Di Iorio

Published in: Journal of Nephrology | Issue 1/2015

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Abstract

Background

Phosphorus is associated with mortality in patients with chronic kidney disease (CKD) not on dialysis, possibly through phosphorus-dependent vascular calcification. Although a phosphorus-restricted diet reduces serum phosphorus, it is unlikely that it reduces vascular calcification progression in CKD. This study evaluated whether a combined strategy of phosphorus-restricted diet and phosphate-binding therapy can reduce the risk of all-cause mortality and/or dialysis initiation by attenuating coronary artery calcification (CAC) progression in non-dialysis CKD patients.

Methods

This was a post hoc analysis of a subgroup of patients from a study that evaluated the impact of two phosphorus binder regimens on hard outcomes in CKD. Patients (n = 113) with stage 3–4 CKD and evidence of CAC on a phosphorus-restricted diet were randomized to receive either calcium carbonate or sevelamer added to their phosphorus-restricted diet. End-points were death for any cause and initiation of dialysis. Patients were monitored to the first event or to conclusion of the 36-month follow-up.

Results

Overall, treatment with calcium carbonate was associated with increased CAC progression and occurrence of all-cause mortality, dialysis initiation, and the composite end-point. After adjustment for confounders, sevelamer use was the only independent predictive factor of reduced risk of each endpoint but only if CAC progression was either absent or moderate. Accelerated progression (annual CAC increase >75th percentile of the study cohort) increased the risk of all-cause mortality and composite end-point (p = 0.01) independently of the use of sevelamer.

Conclusions

A significant reduction in all-cause mortality, dialysis initiation, and composite end-point risk was achieved by combining phosphorus-restricted diet and sevelamer in non-dialysis CKD patients with absent or moderate but not accelerated CAC progression. Future studies should investigate the role of serum phosphorus, the usefulness of a phosphorus-restricted diet, and the appropriateness of current normal ranges of serum phosphorus concentration in relation to events in non-dialyzed CKD patients.
Literature
1.
go back to reference National Kidney Foundation (2003) K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:S1–S201 National Kidney Foundation (2003) K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:S1–S201
2.
go back to reference Block GA, Preston S, Klassen PS et al (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15:2208–2218CrossRefPubMed Block GA, Preston S, Klassen PS et al (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15:2208–2218CrossRefPubMed
3.
go back to reference Young EW, Albert JM, Satayathum S, Goodkin DA et al (2005) Predictors and consequences of altered mineral metabolism: The Dialysis Outcomes and Practice Patterns Study. Kidney Int 67:1179–1187CrossRefPubMed Young EW, Albert JM, Satayathum S, Goodkin DA et al (2005) Predictors and consequences of altered mineral metabolism: The Dialysis Outcomes and Practice Patterns Study. Kidney Int 67:1179–1187CrossRefPubMed
4.
go back to reference Lacson E, Wang W, Hakim RM, Teng M, Lazarus MJ (2008) Associates of mortality and hospitalization in hemodialysis: potentially actionable laboratory variables and vascular access. Am J Kidney Dis 53:79–90CrossRefPubMed Lacson E, Wang W, Hakim RM, Teng M, Lazarus MJ (2008) Associates of mortality and hospitalization in hemodialysis: potentially actionable laboratory variables and vascular access. Am J Kidney Dis 53:79–90CrossRefPubMed
6.
go back to reference KDIGO Clinical Practice Guideline for the Diagnosis (2009) Evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int 76(S113):S1–S130 KDIGO Clinical Practice Guideline for the Diagnosis (2009) Evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int 76(S113):S1–S130
7.
go back to reference Bhuriya R, Li S, Chen S, McCullough PA, Bakris GL (2009) Plasma parathyroid hormone level and prevalent cardiovascular disease in CKD Stages 3 and 4: an Analysis From the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 53(S4):S3–S10CrossRefPubMed Bhuriya R, Li S, Chen S, McCullough PA, Bakris GL (2009) Plasma parathyroid hormone level and prevalent cardiovascular disease in CKD Stages 3 and 4: an Analysis From the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 53(S4):S3–S10CrossRefPubMed
8.
go back to reference Covic A, Kothawala P, Bernal M, Robbins S, Chalian A, Goldsmith D (2009) Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease. Nephrol Dial Transpl 24:1506–1523CrossRef Covic A, Kothawala P, Bernal M, Robbins S, Chalian A, Goldsmith D (2009) Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease. Nephrol Dial Transpl 24:1506–1523CrossRef
9.
go back to reference Tonelli M, Sacks F, Pfeffer M, Gao Z, Curham G (2005) Relation between serum phosphorus level and cardiovascular event rate in people with coronary disease. Circulation 112:2627–2633CrossRefPubMed Tonelli M, Sacks F, Pfeffer M, Gao Z, Curham G (2005) Relation between serum phosphorus level and cardiovascular event rate in people with coronary disease. Circulation 112:2627–2633CrossRefPubMed
10.
go back to reference Kestenbaum B, Sampson JN, Rudser KD et al (2005) Serum phosphorus levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 16:520–528CrossRefPubMed Kestenbaum B, Sampson JN, Rudser KD et al (2005) Serum phosphorus levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 16:520–528CrossRefPubMed
11.
go back to reference Zoccali C, Ruggenenti P, Perna A et al (2011) REIN Study Group: phosphorus may promote CKD progression and attenuate renoprotective effect of ACE inhibition. Am Soc Nephrol 22:1923–1930CrossRef Zoccali C, Ruggenenti P, Perna A et al (2011) REIN Study Group: phosphorus may promote CKD progression and attenuate renoprotective effect of ACE inhibition. Am Soc Nephrol 22:1923–1930CrossRef
12.
go back to reference Mathew S, Tustison KS, Sugatani T, Chaudhary LR, Rifas L, Hruska KA (2008) The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol 19:1092–1105CrossRefPubMedCentralPubMed Mathew S, Tustison KS, Sugatani T, Chaudhary LR, Rifas L, Hruska KA (2008) The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol 19:1092–1105CrossRefPubMedCentralPubMed
13.
go back to reference Kestenbaum B (2007) Phosphorus metabolism in the setting of chronic kidney disease: significance and recommendations for treatment. Semin Dial 20:286–294CrossRefPubMed Kestenbaum B (2007) Phosphorus metabolism in the setting of chronic kidney disease: significance and recommendations for treatment. Semin Dial 20:286–294CrossRefPubMed
15.
go back to reference Ix JH, De Boer IH, Peralta CA et al (2009) Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA. Clin J Am Soc Nephrol 4:609–615CrossRefPubMedCentralPubMed Ix JH, De Boer IH, Peralta CA et al (2009) Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA. Clin J Am Soc Nephrol 4:609–615CrossRefPubMedCentralPubMed
16.
go back to reference Foley RN, Collins AJ, Herzog CA, Ishani A, Kalra PA (2009) Serum phosphorus levels associate with coronary atherosclerosis in young adults. J Am Soc Nephrol 20:397–404CrossRefPubMedCentralPubMed Foley RN, Collins AJ, Herzog CA, Ishani A, Kalra PA (2009) Serum phosphorus levels associate with coronary atherosclerosis in young adults. J Am Soc Nephrol 20:397–404CrossRefPubMedCentralPubMed
17.
go back to reference Russo D, Corrao S, Miranda I et al (2007) Progression of coronary artery calcification in predialysis patients. Am J Nephrol 27:152–158CrossRefPubMed Russo D, Corrao S, Miranda I et al (2007) Progression of coronary artery calcification in predialysis patients. Am J Nephrol 27:152–158CrossRefPubMed
18.
go back to reference Russo D, Miranda I, Ruocco C et al (2007) The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int 72:1255–1261CrossRefPubMed Russo D, Miranda I, Ruocco C et al (2007) The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int 72:1255–1261CrossRefPubMed
19.
go back to reference Russo D, Corrao S, Battaglia Y et al (2011) Progression of coronary artery calcification and cardiac events in patients with chronic renal disease not receiving dialysis. Kidney Int 80:112–118CrossRefPubMedCentralPubMed Russo D, Corrao S, Battaglia Y et al (2011) Progression of coronary artery calcification and cardiac events in patients with chronic renal disease not receiving dialysis. Kidney Int 80:112–118CrossRefPubMedCentralPubMed
20.
go back to reference Di Lullo L, Floccari F, Santoboni A et al (2013) Progression of cardiac valve calcification and decline of renal function in Non-dialysis CKD patients. J Nephrol 26:739–744CrossRefPubMed Di Lullo L, Floccari F, Santoboni A et al (2013) Progression of cardiac valve calcification and decline of renal function in Non-dialysis CKD patients. J Nephrol 26:739–744CrossRefPubMed
21.
go back to reference Di Iorio B, Bellasi A, Russo D (2012) Mortality in kidney disease patients treated with phosphorus binders: a randomized study. Clin J Am Soc Nephrol 7:487–493CrossRefPubMed Di Iorio B, Bellasi A, Russo D (2012) Mortality in kidney disease patients treated with phosphorus binders: a randomized study. Clin J Am Soc Nephrol 7:487–493CrossRefPubMed
22.
go back to reference Achenbach S, Ropers D, Pohle K et al (2002) Influence of lipid-lowering therapy on the progression of coronary artery calcification: a prospective evaluation. Circulation 106:1077–1082CrossRefPubMed Achenbach S, Ropers D, Pohle K et al (2002) Influence of lipid-lowering therapy on the progression of coronary artery calcification: a prospective evaluation. Circulation 106:1077–1082CrossRefPubMed
23.
go back to reference Di Iorio B, Di Micco L, Torraca S et al (2012) Acute effects of very-low-protein diet on FGF23 Levels: a randomized study. Clin J Am Soc Nephrol 7:581–587CrossRefPubMed Di Iorio B, Di Micco L, Torraca S et al (2012) Acute effects of very-low-protein diet on FGF23 Levels: a randomized study. Clin J Am Soc Nephrol 7:581–587CrossRefPubMed
25.
go back to reference Bellasi A, Cozzolino M, Adragao T, Di Iorio B, Russo D (2013) Phosphate binders in moderate chronic kidney disease: where do we stand? J Nephrol 26:993–1000. doi:10.5301/jn.5000258 Bellasi A, Cozzolino M, Adragao T, Di Iorio B, Russo D (2013) Phosphate binders in moderate chronic kidney disease: where do we stand? J Nephrol 26:993–1000. doi:10.​5301/​jn.​5000258
26.
go back to reference Bellasi A, Mandreoli M, Baldrati L et al (2011) Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction. Clin J Am Soc Nephrol 6(4):883–891CrossRefPubMedCentralPubMed Bellasi A, Mandreoli M, Baldrati L et al (2011) Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction. Clin J Am Soc Nephrol 6(4):883–891CrossRefPubMedCentralPubMed
Metadata
Title
Effects of phosphorus-restricted diet and phosphate-binding therapy on outcomes in patients with chronic kidney disease
Authors
Domenico Russo
Antonio Bellasi
Andrea Pota
Luigi Russo
Biagio Di Iorio
Publication date
01-02-2015
Publisher
Springer International Publishing
Published in
Journal of Nephrology / Issue 1/2015
Print ISSN: 1121-8428
Electronic ISSN: 1724-6059
DOI
https://doi.org/10.1007/s40620-014-0071-2

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