Indicator Details — Emerging Topics: Risk of ESRD or Doubling of Serum Creatinine Among Patients in the AASK Studya,b,c
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  • AASK

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Footnotes:
a ESRD p-value < 0.001*

b ESRD or Doubling of Serum Creatinine p-value < 0.001*

c Death before ESRD p-value = 0.43

*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 effect of APOL1 on CKD progression was examined in self-identified black participants with chronic kidney disease attributed to hypertension from the African American Study of Kidney Disease and Hypertension (AASK) Study. Patients were genotyped for the APOL1 risk alleles and over a median follow-up of 9 years, measured for serum creatinine levels every 6 months. The primary outcome is a composite renal outcome of doubling of serum creatinine or end-stage renal disease (ESRD). A recessive genetic model is used 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). The composite outcome occurred in 37% of the low-risk group and was significantly higher (p-value <0.001) in the high-risk group, occurring in 58% of the high-risk patients.
Chart Explanation: The high risk group (patients with 2 copies of APOL1 risk variant) was significantly more likely to progress to ESRD (HR 2.16 p-value <0.001) and to reach the composite of ESRD progression or doubling of serum creatinine (HR 1.88 p-value <0.001). However, APOL1 risk status was not associated with death before ESRD (HR 1.25 p-value 0.43).
The African American Study of Kidney Disease and Hypertension (AASK) is a randomized, double-blind, controlled study in nondiabetic African Americans with hypertensive renal disease. Participants assigned to two levels of target blood pressure and also randomized to receive one of three antihypertensive drugs. The study aim was to determine the effects of blood pressure control level and specific antihypertensive drugs with the primary outcome of progression of hypertensive kidney disease as measured by change in GFR. The trial phase of the study was from 1995-2001 with a cohort follow-up phase from 2002-2007. Participants who provided written consent for DNA collection during the trial were genotyped for data including apolipoprotein L1 (APOL1) markers.

Analyses for this measure were performed in 693 AASK Study patients with usable genotype data. The three measured outcomes included incident end-stage renal disease, a doubling of serum-creatinine levels, and a composite of either of these outcomes. Death before ESRD was also analyzed to identify the possibility of death as a competing risk event in outcome progression. The genetic model presented on this website is a recessive genetic model. The association between APOL1 and the aforementioned outcomes was analyzed with adjusted Cox proportional-hazards models. 
FieldData
Description of MeasureRisk of ESRD or Doubling of Serum Creatinine Among Patients in the AASK Study
Data SourceAASK Multi-center prospective longitudinal cohort study
Type of Data SourcePublic
Data SetAASK summarized data
Health Care System DataNo
Regional or National?National
Demographic GroupSelf-identified African Americans with hypertension, no diabetes, and aged between 18 to 70 years with a GFR of 20 -65 mL/min per 1.73 m2  enrolled in the AASK study
NumeratorComposite outcome of ESRD or doubling of serum creatinine
DenominatorAASK participants with genotyped APOL1 data
Definition of CKDGFR of 20 - 65 mL/min per 1.73 m2 (for entry into study)
Glomerular filtration rateEstimated, MDRD Study equation
Primary Data Source IndicatorSerum creatinine level, incident ESRD, or death
Primary Indicator Method of MeasurementSerum creatinine via blood test; ESRD as indicated by dialysis or transplant, medical record review
Secondary (1) VariableAPOL1 risk variant
Secondary (1) Indicator Method of MeasurementAPOL1 genotype
Frequency of Measurement (Primary)Baseline and every 6 months of the study
U.S. Region Covered by Primary Variable11 clinical centers throughout the United States (Cleveland, Ohio; Nashville, Tennessee; Dallas, Texas; Baltimore, Maryland; Washington, D.C.; Atlanta, Georgia; Los Angeles, California)
Period Currently Available2007
Pending DataNone
Additional Data Items of InterestAdjusted variables (age, gender, European ancestry percentage, baseline GFR)
Limitations of IndicatorCKD-cause not identified
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