Indicator Details — Emerging Topics: Risk of Composite Renal Outcome in Diabetic and Non-diabetic Patients of the CRIC Studya,b,c
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Footnotes:
a All black patients vs. all white patients (with diabetes) p-value<0.001*
All black patients vs. all white patients (without diabetes) p-value<0.001*

b Black patients with 2 copies of APOL1 risk variant vs. all white patients: with diabetes p-value<0.001*
Black patients with 2 copies of APOL1 risk variant vs. all white patients: without diabetes p-value<0.001*

c Black patients with 0 or 1 copy of APOL1 risk variant vs. all white patients: with diabetes p-value= 0.006*
Black patients with 0 or 1 copy of APOL1 risk variant vs. all white patients: without diabetes p-value= 0.01*

*Statistically significant




Studies have identified a gene on chromosome 22 encoding for apolipoprotein L1 (APOL1) that has been associated with a variety of nephropathies. Two variants of the gene, G1 and G2, are considered risk alleles and are associated with increased risk of CKD; these variants are common in people of African ancestry but have not been found in people with European ancestry. It is hypothesized that the gene follows the recessive model, meaning that two copies of the high-risk variant are needed for phenotypic expression. Genotyping of the APOL1 gene in multiple studies suggest about 11%-13% of African Americans have the high-risk 2 APOL1 risk alleles.

The rate of kidney function decline was examined in black and white patients with mild to moderate CKD from the Chronic Renal Insufficiency Cohort (CRIC) Study.  Patients were genotyped for ancestry markers (black or white) and APOL1 risk alleles; serum creatinine was measured annually over 5 years of follow-up. The primary outcomes are rate of kidney function declined as measured by eGFR slope over time and composite renal outcome of ESRD or decline of eGFR by at least 50%.  Using the recessive genetic model to compare patients with 0 or 1 copies of the risk variant (low-risk group) with patients with 2 copies of the risk variant (high-risk group), a multivariate model was used to assess the risk of composite renal outcome.  The model adjusted for demographics, socioeconomics, medical treatment, ACE/ARB use, blood pressure, body mass index (BMI), diabetes, and smoking. Black patients in the high-risk group had a significantly higher risk of ESRD or eGFR decline by at least 50% compared with white patients regardless of diabetes status.
Chart Explanation: Black patients are significantly more likely to develop ESRD or have an eGFR decline of at least 50% when compared with white patients, regardless of diabetes status (with diabetes: HR 1.49 p-value <0.001; without diabetes: HR 1.80 p-value <0.001). Black patients in the high-risk group are significantly more likely to experience a higher rate of the composite renal outcome compared with white patients (HR 1.95 p-value <0.001; HR 2.68 p-value <0.001). Black patients in the low-risk group also have a higher rate of composite renal outcome than white patients (HR 1.40 p-value 0.006; HR 1.57 p-value 0.01).
The Chronic Renal Insufficiency Cohort (CRIC) study is a cohort study of 3,612 individuals 21-74 years of age with CKD of varying severity, recruited from 13 sites in 7 urban centers across the United States in 2003-2007. CRIC was designed to study consequences of CKD with a particular focus on cardiovascular illness like myocardial infarction (heart attack) and stroke. As with all cohort studies, participants may not be representative of all those who live in the communities from which they are recruited.

Analyses for this measure were limited to the 2955 black and white patients with usable genotype data. The composite outcome of "eGFR decline over time or eGFR decline of at least 50% of baseline eGFR" was measured using the MDRD equation. The association between APOL1 and the aforementioned outcomes in blacks and whites was analyzed with mixed-effects models and adjusted Cox proportional-hazards models.
FieldData
Description of MeasureRisk of composite renal outcome in diabetic and non-diabetic CRIC patients
Data SourceCRIC prospective observational cohort study (ancillary)
Type of Data SourcePublic
Data SetCRIC summarized data
Health Care System DataNo
Regional or National?National
Demographic GroupAdults 21 to 74 years old who identify as white or black with an eGFR of 20 - 70 ml/min/1.73 m² (for entry into study)
NumeratorComposite outcome of ESRD or eGFR decline of at least 50% compared to baseline eGFR
DenominatorCRIC participants with genotyped APOL1 data
Definition of CKDEstimated GFR of GFR of 20 - 65 mL/min per 1.73 m2
Glomerular filtration rateEstimated, MDRD Study equation
Primary Data Source IndicatorSerum creatinine level or incident ESRD
Primary Indicator Method of MeasurementSerum creatinine via blood test; ESRD as indicated by dialysis or transplant
Secondary Data Source IndicatorAPOL1 risk variant
Secondary (1) Indicator Method of MeasurementAPOL1 genotype
Period Currently Available2011
Frequency of Measurement (Primary)Annually
Pending DataNone; future visits/ phases schedule
U.S. Region Covered by Primary VariableSeven urban centers throughout the United States (Baltimore, MD; Philadelphia, PA; Cleveland, OH; Detroit, MI; Chicago, IL; New Orleans, LA; Oakland, CA)
Additional Data Items of InterestAdjustment variables of interest (age, gender, clinical site, baseline GFR, education, nephrologist treatment, ACE/ ARB use, systolic blood pressure, BMI, glycated hemoglobin level, smoking status)
Limitations of IndicatorCKD cause unknown, possible “healthy cohort” effect
Analytical ConsiderationsAs with all cohort studies, selection bias and possible confounding
References and Sources:
Suggested Citation:
Centers for Disease Control and Prevention. Chronic Kidney Disease Surveillance System—United States.
website. http://www.cdc.gov/ckd