Serum Phosphate Levels and Mortality Risk among People with Chronic Kidney Disease

Kestenbaum, Bryan; Sampson, Joshua N.; Rudser, Kyle; Patterson, Donald J.; Seliger, Stephen L.; Young, Bessie A.; Sherrard, Donald J.; Andress, Dennis L.

doi:10.1681/asn.2004070602

Cited by 1,075 publications

(826 citation statements)

References 28 publications

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“…Russo et al established in a cohort of predialysis patients that higher phosphorus levels were associated with CAC progression (55). Another study performed in CKD patients observed an association between higher phosphorus levels and mortality (56). Again, hypotheses generated by observational studies require testing in randomized trials, in order in this case to assess the impact of phosphate binders on survival or AoC progression (57).…”

Section: Discussionmentioning

confidence: 99%

Progression of Coronary Artery Calcification and Thoracic Aorta Calcification in Kidney Transplant Recipients

Maréchal

Coche

Goffin

et al. 2012

American Journal of Kidney Diseases

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BACKGROUND: Vascular calcification independently predicts cardiovascular disease, the major cause of death in kidney transplant recipients (KTRs). Longitudinal studies of vascular calcification in KTRs are few and small and have short follow-up. We assessed the evolution of coronary artery (CAC) and thoracic aorta calcification and their determinants in a cohort of prevalent KTRs. STUDY DESIGN: Longitudinal. SETTING PARTICIPANTS: The Agatston score of coronary arteries and thoracic aorta was measured by 16-slice spiral computed tomography in 281 KTRs. PREDICTORS: Demographic, clinical, and biochemical parameters were recorded simultaneously. OUTCOMES MEASUREMENTS: The Agatston score was measured again 3.5 or more years later. RESULTS: Repeated analyzable computed tomographic scans were available for 197 (70%) KTRs after 4.40 ± 0.28 years; they were not available for the rest of patients because of death (n = 40), atrial fibrillation (n = 1), other arrhythmias (n = 4), refusal (n = 35), or technical problems precluding confident calcium scoring (n = 4). CAC and aorta calcification scores increased significantly (by a median of 11% and 4% per year, respectively) during follow-up. By multivariable linear regression, higher baseline CAC score, history of cardiovascular event, use of a statin, and lower 25-hydroxyvitamin D(3) level were independent determinants of CAC progression. Independent determinants of aorta calcification progression were higher baseline aorta calcification score, higher pulse pressure, use of a statin, older age, higher serum phosphate level, use of aspirin, and male sex. Significant regression of CAC or aorta calcification was not observed in this cohort. LIMITATIONS: Cohort of prevalent KTRs with potential survival bias; few patients with diabetes and nonwhites, limiting the generalizability of results. CONCLUSION: In contrast to previous small short-term studies, we show that vascular calcification progression is substantial within 4 years in prevalent KTRs and is associated with several traditional and nontraditional cardiovascular risk factors, some of which are modifiable.

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Section: Discussionmentioning

confidence: 99%

Progression of Coronary Artery Calcification and Thoracic Aorta Calcification in Kidney Transplant Recipients

Maréchal

Coche

Goffin

et al. 2012

American Journal of Kidney Diseases

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“…Visceral myocardial calcification may enhance the risk of arrhythmic events and sudden death. Phosphate excess may increase circulating parathyroid hormone (PTH) and/or decrease 1,25-dihydroxyvitamin D levels (6). Hyperparathyroidism is associated with cardiovascular disease (6).…”

Section: Discussionmentioning

confidence: 99%

“…Phosphate excess may increase circulating parathyroid hormone (PTH) and/or decrease 1,25-dihydroxyvitamin D levels (6). Hyperparathyroidism is associated with cardiovascular disease (6). Animal studies of experimental renal failure have linked PTH excess to intracellular calcium overload, cardiac fibrosis, and impaired myocardial energy production (53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

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Association of Dietary Phosphorus Intake and Phosphorus to Protein Ratio with Mortality in Hemodialysis Patients

Noori¹,

Kalantar-Zadeh²,

Kövesdy³

et al. 2010

Clinical Journal of the American Society of Nephrology

196

127

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Background and objectives: Epidemiologic studies show an association between higher predialysis serum phosphorus and increased death risk in maintenance hemodialysis (MHD) patients. The hypothesis that higher dietary phosphorus intake and higher phosphorus content per gram of dietary protein intake are each associated with increased mortality in MHD patients was examined.Design, setting, participants, & measurements: Food frequency questionnaires were used to conduct a cohort study to examine the survival predictability of dietary phosphorus and the ratio of phosphorus to protein intake. At the start of the cohort, Cox proportional hazard regression was used in 224 MHD patients, who were followed for up to 5 years (2001 to 2006).Results: Both higher dietary phosphorus intake and a higher dietary phosphorus to protein ratio were associated with significantly increased death hazard ratios (HR) in the unadjusted models and after incremental adjustments for case-mix, diet, serum phosphorus, malnutrition-inflammation complex syndrome, and inflammatory markers. The HR of the highest (compared with lowest) dietary phosphorus intake tertile in the fully adjusted model was 2.37. Across categories of dietary phosphorus to protein ratios of <12, 12 to <14, 14 to <16, and >16 mg/g, death HRs were 1.13, 1.00 (reference value), 1.80, and 1.99, respectively. Cubic spline models of the survival analyses showed similar incremental associations.Conclusions: Higher dietary phosphorus intake and higher dietary phosphorus to protein ratios are each associated with increased death risk in MHD patients, even after adjustments for serum phosphorus, phosphate binders and their types, and dietary protein, energy, and potassium intakes.

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“…[97][98][99][100][101] Non-calcium-based phosphate binders may correct hyperphosphatemia and ameliorate abnormalities of the mineral metabolism associated with accelerated kidney disease progression and increased cardiovascular risk. [102][103][104] The finding that phosphate binders reduced proteinuria, an effect that appears to be associated with significant renoprotection in the long term according to recent animal studies (Fig 2), 105,106 along with results of the post hoc analysis of the REIN Study, 51 can be taken to suggest that strategies aimed at lowering phosphate levels might be used in the future to maximize the renoprotective effects of RAAS-blocking agents.…”

Section: Insights From Recent Experimental Studies and Novel Therapeumentioning

confidence: 97%

Blood Pressure, Proteinuria, and Phosphate as Risk Factors for Progressive Kidney Disease: A Hypothesis

Cozzolino

Gentile

Mazzaferro

et al. 2013

American Journal of Kidney Diseases

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Chronic kidney disease (CKD) affects approximately 500 million people worldwide and is increasingly common in both industrialized and emerging countries. Although the mechanisms underlying the inexorable progression of CKD are incompletely defined, recent discoveries may pave the way to a more comprehensive understanding of the pathophysiology of CKD progression and the development of new therapeutic strategies. In particular, there is accumulating evidence indicating a key role for the complex and yet incompletely understood system of divalent cation regulation, which includes phosphate metabolism and the recently discovered fibroblast growth factor 23 (FGF-23)/klotho system, which seems inextricably associated with vitamin D deficiency. The aim of this review is to discuss the links between high blood pressure, proteinuria, phosphate levels, and CKD progression and explore new therapeutic strategies to win the fight against CKD. Am J Kidney Dis. xx(x):xxx. © 2013 by the National Kidney Foundation, Inc. INDEX WORDS:Chronic kidney disease; vitamin D deficiency; blood pressure; proteinuria; phosphate.C hronic kidney disease (CKD) is a silent killer.Four of 5 people with advanced CKD are not aware of the disease until death is imminent and kidney replacement therapy (dialysis or kidney transplantation) is unavoidable. Unfortunately, Ͻ10% of people requiring replacement therapy have access to it, and more than 1 million people worldwide die of untreated kidney failure each year because dialysis or kidney transplantation is unaffordable in most countries. This represents a huge economic burden, with global costs from 2000-2010 surpassing $1 trillion. 1,2 Worsening kidney function is associated with a marked increase in cardiovascular morbidity and mortality 1,3 independent of other risk factors. Coexistent hypertension is present in ϳ80% of patients with CKD and worsens cardiovascular outcomes because only 64% of patients with CKD achieve adequate blood pressure control. 4 As a consequence, only a minority of the hundreds of thousands of patients with stages 3 and 4 CKD reach kidney failure. 5 Proteinuria also is an important prognostic factor in patients with CKD. Although patients with nonproteinuric CKD are at greater risk of cardiovascular mortality than progression to kidney failure, the opposite may be true for the presence of proteinuria. Patients from the REIN (Ramipril Efficacy in Nephropathy) Study who were in the highest tertile of baseline proteinuria (protein excretion Ն3.8 g/d) also experienced the highest rate of glomerular filtration rate (GFR) loss during followup. 6 In addition, although post hoc analysis of RENAAL (Reduction of Endpoints in NIDDM [Non-InsulinDependent Diabetes Mellitus] With the Angiotensin II Antagonist Losartan) showed that 85% of patients with proteinuria with protein excretion Ն3 g/d reached the composite end point of doubling of serum creatinine level or end-stage renal disease (ESRD), only 44% of these patients reached the composite cardiovascular outcome. 7 Besides the we...

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Serum Phosphate Levels and Mortality Risk among People with Chronic Kidney Disease

Cited by 1,075 publications

References 28 publications

Progression of Coronary Artery Calcification and Thoracic Aorta Calcification in Kidney Transplant Recipients

Progression of Coronary Artery Calcification and Thoracic Aorta Calcification in Kidney Transplant Recipients

Association of Dietary Phosphorus Intake and Phosphorus to Protein Ratio with Mortality in Hemodialysis Patients

Blood Pressure, Proteinuria, and Phosphate as Risk Factors for Progressive Kidney Disease: A Hypothesis

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