EAL

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To describe the clinical profiles and outcomes of renal failure patients with late initiation of renal replacement therapies (RR) based on uremic symptoms under intensive treatment prior to the start of RRT (IT).

Inclusion Criteria:

Patients with end-stage renal disease.

Exclusion Criteria:

Severe complications such as ischemic heart disease, cerebrovascular disease, malignancy, infectious disease, liver cirrhosis, malnutrition, more than 70 years of age, could not follow LPD, preferred to be initiated with RRT in spite of less uremic symptoms and families did not understand policies.

Description of Study Protocol:

Recruitment

Referred to a university-based kidney center in Japan.

Design

Before-after study: Patients were treated with the renoprotective therapies and intensive management against uremic states and outcomes were compared before and after treatment.

Intervention

Patients received medical checks one to four times per month over the period of the study (duration not explicitly stated but inferred 60 months from the figures).

Diet: More than 35kcal per kg per day, 0.5g per kg per day of protein, 5.0g per day of sodium chloride, less than 1,600mg to 2,000mg per day potassium and 400mg to 600mg per day of phosphate
"Dietitian advised patients almost every time they visited the hospital"
Erythropoietin (EPO): 6,000 units once a week with occasional iron supplements
Saccharated ferric acid or ferrous sulfate administered if serum iron and ferritin were low
When EPO did not achieve target blood hemoglobin, vitamin B₆, B₁₂, C and folic acid were added
Sodium bicarbonate was used if bicarbonate levels were less than 20mEq per L
Vitamin D₃ administered when serum calcium decreased and intact parathyroid hormone increased
Calcium carbonate (0.5g to 3.0g per day) was given when inorganic phosphate increased
Polystyrene sulfonic acid was given if serum potassium was greater than 5.5mEq per L
Enalapril (5mg per day) was given until initiation of RRT to prevent progression of renal dysfunction
Anti-hypertensives and diuretics were used as indicated to treat symptoms.

Statistical Analysis

Wilcoxon's signed rank test
Spearman correlations between number of uremic symptoms and serum creatinine.

Data Collection Summary:

Timing of Measurements

Patients monitored one to four times per month
24-hour urine collected monthly to measure urea and sodium; when s-Cr levels reached 8.0mg to 9.0mg per dL, patients were advised to create A-V fistula.

Dependent Variables

Body weight
BMI
Mean arterial pressure
Cardiac thoracic ratio
Urinary protein
Serum albumin
24-hour creatinine clearance
Potassium
BUN
S-cr
BUN/Cr
Hb (g per dL)
HCO3 (mEq per Ll)
UCr (g per day)
IP

Independent Variables

Renal replacement therapy.

Description of Actual Data Sample:

Initial N: 13
Attrition (final N): Authors did not explicitly report, but the range of follow-up time was 11 to 69 months
Age: 26 to 62 years (45±12)
Ethnicity: Japanese.

Other Relevant Demographics

10 men, 3 women, with the following renal diseases:

Nine with chronic glomerulonephritis
One with polycystic kidney disease
Two with diabetic nephropathy
One with IgA nephropathy.

Location

Nakama City Hospital, Japan.

Summary of Results:

Variables	Before Mean±SD	After* Mean±SD	P-value
Cardiac thoracic ratio, %	46.6±3.1	52.5±5.2	0.002
24-hour creatinine clearance, ml per minute	15.2±8.4	3.4±0.7	0.003
BUN, mg per dL	48.0±23.5	93.2±20.2	0.0018
S-Cr, mg per dL	5.6±3.2	17.4±3.8	<0.0001
BUN/Cr	9.4±4.1	5.6±1.8	0.0056
Hb, g per dL	10.3±1.8	8.7±1.6	0.018
IP	3.9±0.8	6.5±1.5	<0.001

*After denotes time of initiation of renal replacement therapy, occurring 23.6±16.9 (mean±SD) months after the start of intensive treatment.

** Other outcomes (body weight, BMI, mean arterial pressure, urinary protein, serum albumin, potassium, bicarbonate, urinary creatinine) had no significant pre- or post-differences.

Author Conclusion:

Intensive reno-protective therapies and intensive management to improve uremic states and prevent complications made it possible not only to ameliorate the uremic symptoms and probably delay the progression of chronic renal disease, but also to initiate RRT later under the condition of lower 24-hour CcR and markedly higher s-Cr levels with fewer uremic symptoms and good outcomes after chronic RRT.

Funding Source:

Reviewer Comments:

Patients not a representative sample, refusers of RRT treatment based on creatinine labs
Without comparison group, can not distinguish between effects of treatment vs. effects of time.

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?		No
	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?	N/A
	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?	No
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?	N/A
5.	Was blinding used to prevent introduction of bias?		N/A
	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.)	N/A
	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?		N/A
	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?	N/A
	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?		N/A
	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?	No
	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)?	???
	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