CKD: Hyperphosphatemia (2001)
This review examines causes for increased Phosphorus (P) and increased Calcium x Phosphorus (CaxP), summarizes the association of phosphorus with secondary hyperparathyroidism (SHPT), and data that implicate these factors in CVD in dialysis patients.
Recruitment
Searching methods not described.
Design: Narrative Review
Blinding Used (if applicable): Not applicable
Intervention (if applicable): Not applicable
Statistical Analysis: statistical analysis not completed.
Timing of Measurements: not applicable
Dependent Variables: not applicable
Independent Variables: not applicable
Control Variables: not applicable
Initial N: 87 references
Attrition (final N): 87
Age: not described
Ethnicity:
Other relevant demographics:
Anthropometrics:
Location: worldwide studies
Causes of Increased
• Recommended protein intake of 1.2 g/kg/d
• Limited clearance of conventional HD or CAPD
• Limitations of phosphate binders Hypercalcemia, GI side effects, cost, impaired dissolution Inadequate or improper dosing
• Vitamin D administration
• Use of calcium containing dialysate
• Tertiary hyperparathyroidism
• Patient noncompliance High intake of dairy products and other P-rich foods
• Immobilization
Phosphorus & 2
1. Phosphorus is unique because it exerts a negative impact on vascular calcification directly through CaxP and indirectly through its role in the pathogenesis and progression of 2° hyperparathyroidism.
2. Parathyroid hyperplasia is induced by increased serum P independent of changes in calcium or vitamin D levels and this process occurs rapidly.
3. The effects of increased P persist despite subsequently achieving control of serum PTH levels. Therefore, early and continuous effective control of P is necessary to prevent or inhibit parathyroid hyperplasia and progressive 2° hyperparathyroidism.
Calcification: An overview
1. Abnormal tissue calcification classified as “metastatic” occurring in previously undamaged tissues with increased CaxP or “dystrophic” occurring in injured tissue when serum calcium/phosphorus is normal; the process in renal disease is a combination of these.
2. The calcification process in ESRD is very rapid; with a high prevalence of underlying vascular disease and structural heart disease in patients with severe chronic renal failure.
3. “Uremic” calcification best describes the process of calcification with chronic renal insufficiency with abnormal tissue and abnormal calcium, phosphorus, CaxP, and PTH.
PTH and CVD
Direct or indirect consequences of increased serum P
• Increased CaxP product
• Parathyroid gland hyperplasia
• Increased intact PTH
• Coronary artery calcification
• Death from CAD and sudden death
• Conduction defects, arrhythmias
• Mitral and aortic valve calcification
• Peripheral vascular calcification
• Other calcification: eg. Pulmonary, periarticular
• Calcific uremic arteriolopathy, calciphylaxis
• Increased TG, LDL-chol
Coronary artery calcification in dialysis patients
1. Electron beam computed tomography calcium scoring has been useful in identifying the degree of plaque and the risk for significant CAD; the scores can be used to make recommendations for appropriate risk reduction through lifestyle changes and /or medications, depending on the score.
2. Using data from 2 historical prospective studies of the USRDS, we have reported an increased RR (1.27) of death for patients with a serum phosphorus >6.5 mg/dL relative to those with a phosphorus of 2.4 to 6.5 mg/dL.
3. CaxP >72 was associated with a significantly increased risk of mortality (RR=1.34) relative to those in the reference range of 42 to 52. Also, each 10-mg2/dL2 increase in CaxP was associated with an increased RR (1.11) for sudden death.
Noncardiac vascular calcification
1. Calcification of the abdominal aorta has been associated with increased CaxP.
2. Phosphorus has been associated with atherosclerosis of the carotid artery.
3. Increased PTH is associated with femoral atherosclerosis.
Non-calcium containing phosphorus binders
1. The “ideal” binder would have an increased affinity for binding P, rapid P binding independent of pH, decreased solubility, decreased systemic absorption, lack of toxicity, and a solid oral dose form that is palatable and affordable.
a. polyallylamine HCL marketed as sevelamer HCL has been approved by FDA and is tasteless, odorless and binds P in the GI tract via ion exchange and hydrogen binding and results in less hypercalcemia compared to calcium acetate.
b. vitamin D analogs paricalcitol or Zemplar and doxecalciferol or Hectorol decreased PTH by 30% to 60% with no increase in hypercalcemia or hyperphosphatemia compared to placebo.
° hyperparathyroidism P and Ca x P
We believe it is necessary to change the current management of P, CaxP, and PTH. Traditionally the nephrology community has focused on the impact of these factors on renal osteodystrophy. We believe it is also important to consider the impact on uremic calcification, cardiac death and vascular disease.
Revised Treatment Goals in Dialysis Patients
• Decrease CaxP to < 55 mg2dL2
• Decrease serum P: 2.5-5.5 mg/dL
• Decrease serum Ca to normal range or 9.2-9.6 mg/mL
• Decrease PTH to 100-200 pg/mL
Our recommendations represent a major paradigm shift for dialysis practice, with the goal of substantially decreasing the increased morbidity and mortality rate of patients with ESRD.
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| University/Hospital: | University of Michigan |
The recommendations for serum P and calcium seem appropriate for Pre ESRD patients as well which could be achieved with lower dietary phosphorus which would require limiting protein intake as well.
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Quality Criteria Checklist: Review Articles
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| Relevance Questions | |||
| 1. | Will the answer if true, have a direct bearing on the health of patients? | Yes | |
| 2. | Is the outcome or topic something that patients/clients/population groups would care about? | Yes | |
| 3. | Is the problem addressed in the review one that is relevant to dietetics practice? | Yes | |
| 4. | Will the information, if true, require a change in practice? | Yes | |
| Validity Questions | |||
| 1. | Was the question for the review clearly focused and appropriate? | Yes | |
| 2. | Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? | No | |
| 3. | Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? | No | |
| 4. | Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? | No | |
| 5. | Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? | Yes | |
| 6. | Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? | Yes | |
| 7. | Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? | No | |
| 8. | Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? | Yes | |
| 9. | Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? | Yes | |
| 10. | Was bias due to the review's funding or sponsorship unlikely? | Yes | |