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CKD: Hyperphosphatemia (2001)


Martin KJ, Gonzales EA. Vitamin D analogues for the management of secondary hyperparathyroidism.  Am J Kidney Diseases 2001;38 (suppl 5):S34-S40.

Worksheet created prior to Spring 2004 using earlier ADA research analysis template.
PubMed ID: 11689385
Study Design:
Narrative Review
R - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
This paper reviews newer vitamin D analogues used to treat secondary hyperparathyroidism in patients with chronic renal failure.


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:  33 references

Attrition (final N):  33

Age:  not mentioned

Ethnicity:  not mentioned

Other relevant demographics:


Location:  worldwide studies


Summary of Results:

19-Nor-1,25 (OH)2 D2 (paricalcitol)

1. Animal studies

a. suppresses PTH secretion in both normal and uremic animals while at the same time a considerably lesser ability to increase serum calcium or phosphorus.

b. Biological effect potency vs. Calcitriol

Suppresses PTH 1/3

Increases serum calcium 1/10

Increases serum phosphorus 1/10

2. Clinical trials

a. under the conditions of the study, a 60% decrease in PTH levels was observed, with serum calcium values remaining in the normal range.

b. episodes of hypercalcemia occurred when intact PTH values were suppressed to near 100 pg/mL, levels considered undesirably low.

c. fewer episodes of hyperphosphatemia occurred in studies compared with calcitriol.

1-a- (OH) D2 (doxercalciferol)

1. Animal studies

a. 1-a- (OH) D2 was less toxic than 1-a- (OH) D3 , however, there appeared to be similar potency in terms of suppressing PTH, increased calcium absorption from the intestine and increased serum phosphate.

2. Clinical studies:

a. this analog has been successfully used to treat patients with secondary hyperparathyroidism on dialysis therapy and in oral form, effective in decreasing PTH with minimal effects on serum calcium and phosphorus.

b. substantial number of episodes of hypercalcemia and hyperphosphatemia.

Author Conclusion:

Vitamin D analogues are now well established for the control & therapy of hyperparathyroidism in chronic kidney disease.

We have begun to understand some of the mechanisms involved in the lower toxicity of vitamin D analogues; for example,

19-nor-1,25-dihydroxyvitamin D2 does not appear to increase vitamin D receptor in the intestine, whereas the native compound, 1,25(OH)2 D clearly upregulates its receptor.

This might explain the differences between these sterols in the intestinal absorption of calcium. It is possible that in the future, more potent or more selective analogues may be developed as we gain increasing understanding of the mechanisms of action of these agents and how these can be exploited to achieve improved clinical utility.

Funding Source:
University/Hospital: SLU School of Medicine
Reviewer Comments:
Paricalcitol appears to be a better choice for treating secondary hyperparathyroidism than either calcitriol or doxercalciferol. However, serum calcium and phosphorus as well as PTH must be monitored whatever form of vitamin D is used.
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? Yes
  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