EAL

CKD: Potassium (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to evaluate the impact of the initial laboratory data (prior to initiation of dialysis) on survival in chronic dialysis patients. The data was intended to provide potential reversible predictors of survival for dialysis patients.

Inclusion Criteria:

Patients residing and receiving dialysis in one geographic area of Japan from one of 27 dialysis centers.
Chronic hemodialysis was initiated between 1971 and the end of 1990 in Okinawa, Japan.
Laboratory and clinical data available at the initiation of dialysis.

Exclusion Criteria:

None mentioned.

Description of Study Protocol:

Recruitment: Subjects were from a regional dialysis registry in the Southern islands of Japan. Patients with available laboratory and clinical data at initiation of dialysis from a total of 1982 registered patients between 1971 and 1990.

Design: Retrospective Cohort Study.

Blinding Used (if applicable): Not applicable.

Intervention (if applicable):

Initial laboratory and clinical variables related to survival.
Patients were followed until death, renal transplant, transfer to another location, or end of 1993, whichever came first.

Statistical Analysis: (SAS package)

Base analysis: characteristics of patients who had died were compared with those who survived. Cox proportional hazard analysis was done by adjusting for sex, age, year of dialysis, and presence of diabetes mellitus for each variable.

Similar analysis repeated for each variable by adding remaining laboratory variables.

Kaplan-Meier method for survival curves.

Student's t-test (paired and nonpaired) and chi-squared to compare discrete variables between groups.

Data Collection Summary:

Timing of Measurements: Laboratory and clinical data at initiation of dialysis, reviewed by primarily one of the investigators.

Dependent Variables:

Survival versus death.

Independent Variables:

Biochemical data: BUN, serum creatinine, total protein, serum albumin, total cholesterol, triglycerides, hematocrit, and serum electrolytes (sodium, potassium, calcium and phosphorus).
Clinical data: height, weight, blood pressure.

Control Variables:

age
sex
year of dialysis
presence of diabetes mellitus.

Description of Actual Data Sample:

Initial N: 1491 (75.2% of total registered dialysis patients)

Attrition (Final N): 644 deaths by end of study (43.2% of initial n)

Age: 50.9 + 0.4 years (range: 1.9 to 90.5 years)

Ethnicity: assumed to be Japanese

Other Relevant Demographics: none

Anthropometrics: reported below

Location: Okinawa, Japan

Summary of Results:

Overall cumulative probability of survival of study group versus total group	n=1491	N=1982
1 year	0.884	0.884
5 years	0.668	0.683
10 years	0.515	0.545
15 years	0.421	0.438

Causes of kidney disease	n=1491	%
Glomerulonephritis	n=886	59.4
Diabetic nephropathy	n=345	23.1
Hypertensive nephropathy	n=89	6.0
Polycystic kidney disease	n=31	2.1
Lupus nehpritis	n=29	2.0
Other	n=111	7.4

Causes of death (n=644)	%
Infection	16.0
Withdrawal	18.0
Cardiac	32.0
Sudden death	5.0
Vascular	13.0
Other	16.0

Comparison of significant clinical baseline variables between survivors and patients who died during observation period:

Variables	n	Surviving patients (n=847)	Patients who died (n=644)	p value
BUN (mg/dL)	1491	122.4 + 1.5	111.0 + 1.4	0.0001
Serum creatinine (mg/dL)	1485	14.2 + 0.2	11.7 + 0.2	0.0001
Total protein (g/dL)	1172	6.2 + 0.04	6.0 + 0.03	0.0003
Serum albumin (g/dL)	1030	3.5 + 0.02	3.2 + 0.02	0.0001
Serum potassium (mEq/L)	1406	4.5 + 0.03	4.7 + 0.04	0.0021
Serum sodium (mEq/L)	1255	136.8 + 0.2	134.9 + 0.3	0.0001
Serum phosphate (mg/dL)	1052	7.5 + 0.1	7.0 + 0.1	0.0003
Body height (m)	822	1.56 + 0.004	1.54 + 0.005	0.0001
Body weight (kg)	966	53.9 + 0.5	52.1 + 0.5	0.0015
Diastolic blood pressure (mm Hg)	940	85.6 + 0.8	81.5 + 0.9	0.0001

No significant differences were found between baseline values for serum calcium, total cholesterol, triglycerides, hematocrit, or systolic blood pressure between groups.

Significant independent predictors (covariates) of survival, after adjustment for age, sex, year of dialysis, and diabetes mellitus (control variables) and each variable adjusted for all the rest:

Risk Ratio

P value

Serum albumin (g/dL)

0.577

0.0025

Serum potassium (mEq/L)

1.291

0.0138

Serum sodium (mEq/L)

0.966

0.0202

Serum albumin (g/dL)	Relative Risk (95% CI)
<3.5	1.00
3.5-3.9	0.58 (0.40 – 0.82)
4.0-4.4	0.33 (0.16 - 0.68)
>4.5	0.19 (0.07 – 0.56)

Serum potassium (mEq/L)	Relative Risk (95% CI)
<3.5	1.00
3.5 – 4.4	1.29 (1.05 – 0.58)
4.5 – 5.4	1.67 (1.11 - 2.50)
>5.5	2.15 (1.17 – 3.96)

Serum sodium (mEq/L)	Relative Risk (95% CI)
<132	1.00
132 – 135	0.83 (0.71 – 0.98)
136 – 139	0.70 (0.51 - 0.96)
>140	0.58 (0.36 – 0.93)

Calculated survival curves show that prognosis was poor for those with baseline values of albumin < 3.5 g/dL, higher serum potassium, and lower serum sodium. Those with low serum albumin had death occurring at significantly shorter duration of dialysis than other subgroups.

Author Conclusion:

Results from this study demonstrate that hypoalbuminemia, hyperkalemia, and hyponatremia at the initiation of dialysis are significant, independent predictors of death. These variables are potentially treatable if underlying mechanisms are investigated.

Funding Source:

Government:

Ministry of Health and Welfare (Japan)

Industry:

Baxter Company (Japan)

Pharmaceutical/Dietary Supplement Company:

University/Hospital:

University of The Ryukyus (Okinawa), Okinawa Chubu Hospital, Okinawa Kyodo Hospital, Urasoe Sogo Hospital, Okinawa Dai-ichi Hospital, Okinawa Prefectural Hokubu Hospital (Japan)

Reviewer Comments:

The strongest predictor of death in this retrospective study at the initiation of dialysis was serum albumin. A low serum albumin is a marker for protein calorie malnutrition. Since this study was retrospective in design, the results do not show cause and effect.

Data was collected on patients beginning dialysis from 1971 to 1990, with 1993 designated as end of study. Since baseline data was compared to survival outcome, there is no consideration for improvements in treatment methods over the course of 22 years, nor for patient compliance.

Impressive collection of data in large sample with strong statistical analyses.

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)	N/A
	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)	N/A

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?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	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?	???
	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?		???
	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?	Yes
	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?		???
	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)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	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