CKD: Progression and Diabetes (2001)

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

This is a sub study of the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study to evaluate the clinical and biochemical correlates of regression of proteinuria in subjects with type 1 diabetes mellitus.

Inclusion Criteria:

Type 1 diabetes mellitus diagnosed at <16 yr of age, between 1950 and 1980 at Children’s Hospital of Pittsburgh.

Exclusion Criteria:

Of 146 patients with Diabetic Neuropathy (DN) at baseline, exclusions were:

  • 13 had incomplete follow-up data.
  • 9 died without developing renal failure
  • 32 who developed renal failure were excluded so that change in risk factors could be appopriately analyzed.
Description of Study Protocol:

Recruitment:  Type 1 diabetes mellitus diagnosed at <16 yr of age, between 1950 and 1980 at Children’s Hospital of Pittsburgh. Pateints were assigned into a normal AER range or DN range, based on a minimum of two or three AER values in the same range at each evaluation cycle.

Design: Cohort Study.

Blinding Used (if applicable): not applicable

Intervention (if applicable):  not applicable

Statistical Analysis: Statistical analysis focused on the 78 individuals without subsequent renal failure or death who provided complete quantitative studies at the four-year follow-up.  Included a multiple logistic analysis that also controlled for length of follow-up, multiple linear regression for LDL-C and systolic blood pressure as independent predictors of change in log AER.

 

Data Collection Summary:

Timing of Measurements: Subjects were underwent a battery of tests at biennial exams:  baseline, 2-year, and 4-year examinations.

Dependent Variables: Albumin excretion rate (AER)

Urine albumin: 3 collections (24-hr, one overnight, one 4-hr) over the 2 wk before each biennial exam; baseline: cycle 1, 2-yr: cycle 2 and 4-yr: cycle 3.

Validation of urine albumin with urine creatinine:

a. men: mg creatinine/24 hr = 28 – 0.2 x (age in yr) x (wt in kg)

b. women: mg creatinine/24 hr = 28 - 0.2 x (age in yr) x (wt in kg) x 0.85.

Subjects were assigned to a group based on albumin excretion rate:

a. 20 to <200 µg/min

b. diabetic nephropathy range: >200 µg/min e.g. >288 mg/24 hr or >500 mg/d

c. regression of nephropathy defined as: decrease in median (middle) albumin excretion rate value derived from all 3 samples at each cycle 2 or cycle 3.

Independent Variables: not specified

Control Variables: not specified

Description of Actual Data Sample:

Initial N: Among 658 subjects with type 1 diabetes mellitus, 148 had diabetic nephropathy at baseline, 9 subsequently died without renal failure and 13 were lost to follow-up.

Attrition (Final N): Of the 124 subjects with at least survey followup data, 32 (24%) developed renal failure, and 78 of the remaining 92 provided follow-up data; 45 of the 78 reported an improvement in albumin excretion rates and 7 of the 45 had a 10-fold improvement.

Age: Mean age of original 658 patients in Pittsburgh EDC Study was 28 years.

Ethnicity: 98% white

Other Relevant Demographics: mean duration of diabetes, 20 years

Anthropometrics: not specified

Location: Pittsburgh, PA area.

 

Summary of Results:

Changes in biochemical risk factors over cycles in which albumin excretion rates decreased 10-fold
 

Nonregressors

regressors
 

n=71

n=7

HbA1c,%

0.9±2.1 1.0±1.2

LDL-C, mg/dL

1.5±30.1 30.9±16.6*

TG, mg/dL

-3.0±11.5 -9.4±15.0

Serum creatinine (mg/dL)

0.3±0.6 0.3±0.4

urinary albumin rate (µg/min)

131±1,456

-715±663.0**

GFR (ml/min)

-20.9±30.5  -21.3±19.7

* P<0.01 **P<0.001

Changes in blood pressure and biochemical risk factors over 4 years.
 

Increased AER

Decreased AER
 

n=33

n=45

Blood pressure, (mm Hg) Systolic 

12.3+18.4 -0.02+15.0*

Diastolic 

3.8+10.3 -3.2+12.0*

HbA1c, % 

1.0+1.8 0.7+2.2

LDL-C (mg/dL) 

8.8+26.6 -9.5+31.2**

TG, mg/dL 

-1.7+77.3  -9.7+85.8

GFR (ml/min)

-16.2+31.5 -24.6+28.7

*P>0.05, **P<0.01.

Author Conclusion:

Our data indicate that diabetic nephropathy as manifested by an albumin excretion rate >200 µg/min regressed to some degree in 34% of subjects with type 1 diabetes mellitus without systematic application of corrective measures.

Significant clinical and biochemical correlates predictive of such reversal or amelioration of diabetic nephropathy are stabilization or improvement in blood pressure by any means, and a decrease in plasma LDL-cholesterol.

The decrease in the albumin excretion rate was not accompanied by an improvement in GFR. Thus, long-term follow-up of these individuals will be needed to help determine if the improvement in the albumin excretion rate is permanent and the loss of renal function is halted.

Funding Source:
Government: NIH
University/Hospital: Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, University of Pittsburgh
Reviewer Comments:

Extensive discussion of the limits and findings of this epidemiological incident cohort of IDDM subjects, and implications for further studies.

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? ???
  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? ???
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  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? Yes
  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? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  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.) Yes
  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? ???
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments described? No
  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? Yes
  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? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  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? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes