CKD: Hyperphosphatemia (2001)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:
To investigate the management of disturbed calcium metabolism in uraemic patients.
Inclusion Criteria:
Article inclusion criteria not specifically mentioned.
Exclusion Criteria:
Article exclusion criteria not specifically mentioned.
Description of Study Protocol:

Recruitment:  Article selection methods not described

Design:  Narrative Review

Blinding Used (if applicable):  not applicable

Intervention (if applicable):  not applicable

Statistical Analysis:  statistical analysis not completed

 

Data Collection Summary:

Timing of Measurements:  not applicable

Dependent Variables:  not applicable

Independent Variables:  not applicable

Control Variables:  not applicable

Description of Actual Data Sample:

Initial N:  73 references

Attrition (final N):  73

Age:  not mentioned

Ethnicity:  not mentioned

Other relevant demographics:

Anthropometrics:

Location:  worldwide studies

Summary of Results:

Background

1. Chronic renal failure is characterized by diminished synthesis of, and resistance to, the active vitamin D metabolite [1,25(OH)2D3] or calcitriol.

a. 1a-hydroxylase, the rate-limiting enzyme for its biotransformation into 1,25(OH)2D3 is located in the kidney, primarily in the distal tubule.

b. the main stimulatory signal is PTH and the main inhibitory signal is hyperphosphatemia (both of these signals are altered in renal failure).

c. 1a-hydroxylase becomes substrate dependent in patients with renal failure, e.g. increased 25(OH)2D3 will result in a increased rate of transformation into 1,25(OH)2D3.

d. calcitriol is less effective in uremia, probably due to decreased expression of vitamin D receptors particularly in parathyroid glands.

Indications for administration of vitamin D

1. Two different situations in which administration of active vitamin D (calcitriol) is indicated in renal patients:

a. prevention of 2° hyperparathyroidism by hormonal substitution [administering active vitamin D (calcitriol or related compounds)].

1) indicated with increased iPTH and treated with relatively small doses of calcitriol.

b. treatment of 2° hyperparathyroidism by suppressing parathyroid gland overactivity.

1) requires larger doses of calcitriol which may be ineffective because the parathyroid gland may be hyporesponsive; also, because of abnormal calcium sensing and hyperphosphatemia.

Prevalence of hyperparathyroidism

1. iPTH levels, 2-3 times above the normal range are found in ~39% of patients on dialysis.

2. extreme hyperparathyroidism necessitates parathyroidectomy and is related to the level of PTH upon initiation of dialysis, thus the importance of early treatment of hyperphosphatemia and iPTH.

Deficiency of the parent compound (cholecalciferol) vs. deficiency of active vitamin D [1,25(OH)2D3]

1. Administration of cholecalciferol when plasma 25(OH)D3 >20 nmol/L and <50 nmol/L decreases PTH and stimulates active calcium transport in the GI tract, suggesting that this range of vitamin D constitutes a state of latent vitamin D deficiency.

a. 60% of patients admitted for chronic dialysis in Heidelberg, Germany had 25(OH)D3 <60 nmol/L; the causes for this are insufficient exposure to sunlight, resistance of the skin to sunlight, low dietary intake of vitamin D and loss of protein bound vitamin D with proteinuria.

2. Recommend 1000 U of vitamin D3 (cholecalciferol)/d to increase plasma 25(OH)D3 >50 nmol/L.

Mode of administration of active vitamin D

1. Intravenous administration of calcitriol caused acute decrease of iPTH before there were any changes in ionized calcium, however the cost is greater than oral.

2. Oral calcitriol increases serum levels of vitamin D for 36 hours and suppresses iPTH between 48 and 96 hours of dosing.

Calcitriol analogues

1. Calcitriol is difficult and costly to synthesize, therefore an analogue, 1a-hydroxycalcidol has been developed. This analogue is transformed to 1,25(OH)2D3 by the liver.

Non-hypercalcemic analogues of vitamin D

1. Oxacalcitriol causes less hypercalcemia than calcitriol and decreases synthesis of PTH.

2. 19-nor-a-25dihydroxyvitamin D2 (paracalcitol) is given by IV; one study showed that 68% of patients receiving paracalcitol had >30% decrease in PTH compared to placebo.

Practical recommendations

Algorithms for prophylaxis of 2° hyperparathyroidism

1. Monitoring plasma chemistry

a. monitor plasma calcium, albumin, phosphate, 25(OH)D3, aluminum and iPTH

2. Prophylactic measures:

a. if 25(OH)D3 is <50 nmol/L give 100 U cholecalciferol/d

b. if plasma calcium is decreased or plasma phosphate increased, give calcium carbonate (0.5 – 1.5 g) with each meal.

c. if iPTH is consistently >12-18 pmol/L (2 to 3 times normal) and plasma calcium and phosphate are normal, give calcitriol 0.125-0.25 mg/d or equivalent doses of 1a –calcidiol

d. if iPTH is consistently >20 pmol/L, normalize plasma calcium and phosphate.

e. if plasma phosphate is increased , give calcium carbonate with meals and decrease dietary phosphate.

f. if plasma calcium and phosphate have been normalized, increased doses of calcitriol (0.5 – 3 µg) or alternative active vitamin D preparations daily or 1-3 times/wk, depending on iPTH.

g. if iPTH decreases <20 pmol/L, interrupt administration of calcitriol, remeasure iPTH and determine change in vitamin D dosing.

Author Conclusion:
Funding Source:
University/Hospital: University of Heidelberg
Reviewer Comments:

Good review of vitamin D metabolism in chronic kidney disease, the causes of deficiency of active vitamin D in kidney disease, and the prevention and treatment of secondary hyperparathyroidism.

Suggestions for monitoring serum calcium, phosphorus, iPTH and vitamin D dosing are also included.

The important take home point from this review is that vitamin D deficiency is unique for each patient with chronic kidney disease and thus treatment needs to be individualized.
Quality Criteria Checklist: Review Articles
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