Metabolic Syndrome Predicts Worsening CKD in Hypertensive African Americans

Marlene Busko

November 23, 2006

November 23, 2006 (San Diego) — Having metabolic syndrome conferred a 38% increased risk for chronic kidney disease (CKD) progression to a 50% decline in glomerular filtration rate (GFR), end-stage renal disease (ESRD), or death in a study of hypertensive African Americans. These findings, from the African-American Study of Hypertension and Kidney Disease (AASK) trial, were presented in an oral session at the American Society of Nephrology (ASN) Renal Week 2006.

Janice P. Lea, MD, from Emory University School of Medicine, in Atlanta, Georgia, and the principal investigator for the AASK trial, told the audience: "This is the first prospective study reporting that metabolic syndrome predicts the rate of CKD progression. . . . Our findings may explain some of the variability observed in the progression of ESRD and may provide new targets to treat in CKD." She also noted that studies with more specific measures of insulin resistance are needed.

High-Risk Cohort

Dr. Lea explained that metabolic syndrome, a cluster of characteristics associated with obesity and high risk for cardiovascular disease, is very prevalent among African Americans. She added that the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III definition of metabolic syndrome is 3 or more of the following risk factors: elevated triglycerides (> 150 mg/dL), low HDL cholesterol (< 50 mg/dL in women or < 40 mg/dL in men), elevated BP (> 130/85 mm Hg), elevated fasting glucose (> 110 mg/dL), or abdominal obesity measured by waist circumference (which was not examined in the current analysis). Two major studies have provided evidence that metabolic syndrome is associated with incident CKD (Kurella M et al. J Am Soc Nephrol. 2005;16:2134-40; and Chen J et al. Ann Intern Med 2004;140:167-74).

To date, no study has looked at how metabolic syndrome affects CKD progression, which was the objective of the current post hoc analysis.

The AASK study enrolled African Americans who had hypertension and a glomerular filtration rate (GFR) of 20 to 65 mL/min. It excluded subjects who had known diabetes or fasting blood-glucose levels higher than 140 mg/dL. The trial, which had a 4.1-year follow-up, randomized subjects to 1 of 2 blood-pressure goals and to 1 of 3 antihypertensive regimens.

A total of 1094 patients were enrolled in AASK; this study examined 842 of these who did not have missing triglyceride data. At baseline, the subjects had a mean age of 54.6 years and a GFR of 45.6 ± 13 mL/min per 1.73 m2. A total of 24.7% of them had metabolic syndrome, defined according to NCEP criteria other than obesity. Obesity was not included in this study because of a lack of waist-circumference data, but 40.6% of the study subjects had a body-mass index (BMI) greater than 30 (ie, were obese).

Worse Outcomes With 3 or More Risk Factors

The study outcome was the time to the clinical composite of a 50% or 25-mL/min decrease in GFR (measured by 125-I-iothalamate clearance), the development of ESRD, or death. Having 3 or more of the risk factors that define metabolic syndrome predicted an increased risk of renal-disease progression, but this association was not found when only 1 component of metabolic syndrome was present. This result was independent of blood-pressure goal or assigned antihypertensive therapy.

Risk of CKD Progression

Risk Factors
HR (95% CI)
Blood glucose > 110 mg/dL
1.2 (0.9 – 1.6)
Triglycerides > 150 mg/dL
1.22 (0.9 – 1.6)
HDL cholesterol < 40 mg/dL
1.1 (0.8 – 1.3)
BMI > 30
.95 (0.7 – 1.2)
Systolic BP > 150 mm Hg
1.1 (0.9 – 1.4)
Metabolic syndrome
1.38 (1.1 – 1.8)
Adjusted for age, sex, BMI, GFR, urine protein/creatinine

"Metabolic syndrome can contribute to worsening kidney disease," Dr. Lea summarized in a statement to the press. "That's important, because if we can reduce the severity of metabolic syndrome through diet and medication, it may help to reduce the rate of progressive kidney disease — and thus delay ESRD and the need for dialysis therapy, which is very costly and debilitating."

Renal Week 2006: ASN Annual Meeting: Abstract F-FC086.


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