CKD: Anemia (2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To study the effects of r-HuEPO in the treatment of anemia of progressive renal failure, and to develop treatment strategies which take into account the particular need of outpatients for not too frequent controls and the necessity for most treating institutions to limit the number of regular visits, as cost and personal limitations have to be respected.

Inclusion Criteria:
  • Diagnosis or anemia from kidney disease.
  • Hg <10 g/dl
  • Patient’s physician recommended treating low hemoglobin
Exclusion Criteria:
  • 7 subjects excluded that required renal replacement therapy during the study
Description of Study Protocol:

Recruitment

130 patients from 20 medical centers with experience in the treatment of renal failure.

Design:  Nonrandomized Longitudinal Clinical Study

  • Study period of 3 months.
  • Target goal for Hg: 11 to 12 g/dL.
  • Hg determinations q 2 wk and monthly complete blood chemistries.
  • Blood samples collected and analyzed at the outpatient bases.

Blinding used (if applicable):  not applicable

Intervention (if applicable):

  • Subcutaneous dose of 10,000 U EPOETIN/wk.
  • Doses of EPOETIN adjusted based on q 4 wk hemoglobin differences of – 1 or +1 g/dL; doses were changed by 4,000 U.
  • Iron substitutuin (Fe-sulfate or Fe-gluconate equivalent to ~ 300 mg Fe/day given whenever feritin levels were below 100 ng/ml.

Statistical Analysis:

  • mean +/- standard error of the mean (SEM)
  • student's t test followed by a Bonferroni procedure

 

Data Collection Summary:

Timing of Measurements:

  • Hb checked every 2nd week and monthly
  • CBC checked monthly 

    Dependent Variables:

    • Blood samples measured at the outpatient bases and analyzed for Hg, serum creatinine, serum ferritin, serum calcium, phosphorus, potassium and sodium, platelets.
    • Monitoring of blood pressure and thromboembolic complications
    • Changes in serum creatinine, hemoglobin, hematocrit, platelets, leukocytes, ferritin, sodium, potassium, calcium, phosphate

    Independent Variables:

    • Subcutaneous dose of 10,000 U EPOETIN/wk

    Control Variables:

    None noted

     

  • Description of Actual Data Sample:

    Initial N: 130, 48% male, 52% female

    Attrition (final N): 123 (95%) 7 subjects required renal replacement therapy during the study; the data from these subjects was not included

    Age:  mean age, 56.6 years (range 18-84)

    Ethnicity: not reported

    Other relevant demographics:  mean Weight, kg 68.4+1.25 (+ 1.25 SEM), mean Creatinine, mg/dL 6.2+0.2 (+ SEM)

    Anthropometrics:

    Location:  Austria

    Summary of Results:

    Variables

    Treatment Group

    Measures and confidence intervals*

    Statistical Significance of Group Difference

    Hemoglobin increase

       ~8.4 to 10.8 g/dl

    P < 0.05

    Platelet increase at one month

    9.0 to ~9.5

    P < 0.05

    Serum ferritin decrease 180 ng/ml to ~115 ng/ml P < 0.05

    *The article did not report the actual SEM.

    Other Findings

    • Creatinine increased to 6.6 g/dL but the slope of the line for the reciprocal serum creatinine curve did not change. Treatment did not alter the progressive deterioration in renal function.
    • Hypertension: No significant alterations of blood pressure observed.  Preexisting antihypertensive therapy adjusted occasionally. 
    • Platelets: significantly increased at 1 month (P<0.05), but values remained within normal range.  Platelets after the 2nd month were not significant greater than baseline values.
    • Serum electrolytes: No significant changes in serum calcium, phosphorus, potassium, sodium.
    • Serum ferritin: Significant decrease from ~180 ng/ml to ~115 ng/ml (P<0.05) despite iron substitution in 40% of patients.
    • Leukocytes:  no significant change
    • No signs of thromboembolic complications.
    • No side effects reported.

     

    Author Conclusion:

    The results of this multicenter trial demonstrated that using a simple once/wk subcutaneous treatment regime of 9,000 +/- 4000 U of r-HuEPO can be administered safely and effectively in predialysis patients.   This therapy resulted in an hemoglobin increase from ~8.4 g/dl to 10.8 g/dl (p< 0.05).

    Although the follow-up period was limited to 3 months, there were not the usual side effects (development of more severe hypertension or thrombi). The most likely explanation was the slow and constant rise of hemoglobin that appears to avoid hypertensive episodes. Even though there was a transient rise in platelets, no thrombi developed, perhaps because of the short study period.

    The lack of side effects must be looked at with caution as long-term results may be different.

    Funding Source:
    Industry:
    Cilag GmbH
    Pharmaceutical/Dietary Supplement Company:
    Reviewer Comments:

    It would have been interesting to ask the subjects questions regarding energy levels, overall sense of well-being, etc after 3 months of EPO treatment.

    Possibility of differences in lab analyses not reported- 20 labs participating.

    Abstract reports baseline value for hemoglobin of 9.0 g/dl, but the figure indicates value of ~8.4 g/dl.

    Quality Criteria Checklist: Primary Research
    Relevance Questions
      1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
      2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
      3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
      4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
     
    Validity Questions
    1. Was the research question clearly stated? Yes
      1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
      1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
      1.3. Were the target population and setting specified? Yes
    2. Was the selection of study subjects/patients free from bias? Yes
      2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
      2.2. Were criteria applied equally to all study groups? Yes
      2.3. Were health, demographics, and other characteristics of subjects described? Yes
      2.4. Were the subjects/patients a representative sample of the relevant population? Yes
    3. Were study groups comparable? N/A
      3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
      3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
      3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
      3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
      3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
      3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
    4. Was method of handling withdrawals described? Yes
      4.1. Were follow-up methods described and the same for all groups? Yes
      4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
      4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
      4.4. Were reasons for withdrawals similar across groups? Yes
      4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? Yes
    5. Was blinding used to prevent introduction of bias? No
      5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
      5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) No
      5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
      5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
      5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
    6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
      6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
      6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
      6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
      6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
      6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
      6.6. Were extra or unplanned treatments described? Yes
      6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
      6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
    7. Were outcomes clearly defined and the measurements valid and reliable? Yes
      7.1. Were primary and secondary endpoints described and relevant to the question? Yes
      7.2. Were nutrition measures appropriate to question and outcomes of concern? N/A
      7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
      7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
      7.5. Was the measurement of effect at an appropriate level of precision? Yes
      7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
      7.7. Were the measurements conducted consistently across groups? Yes
    8. Was the statistical analysis appropriate for the study design and type of outcome indicators? No
      8.1. Were statistical analyses adequately described and the results reported appropriately? No
      8.2. Were correct statistical tests used and assumptions of test not violated? ???
      8.3. Were statistics reported with levels of significance and/or confidence intervals? No
      8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? No
      8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
      8.6. Was clinical significance as well as statistical significance reported? Yes
      8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
    9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
      9.1. Is there a discussion of findings? Yes
      9.2. Are biases and study limitations identified and discussed? Yes
    10. Is bias due to study's funding or sponsorship unlikely? ???
      10.1. Were sources of funding and investigators' affiliations described? Yes
      10.2. Was the study free from apparent conflict of interest? No