Adiposity markers predict decline in kidney function

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Three different measures of adiposity are independent risk factors for decline in glomerular filtration rate (GFR) and death, concludes a meta-analysis in the British Medical Journal.

The analysis included individual-level data on nearly 5.5 million adults enrolled in 39 international general population cohorts, drawn from the Chronic Kidney Disease Prognosis Consortium. Eighteen cohorts included nearly 92,000 participants with CKD, while six cohorts included approximately 84,000 individuals at high cardiovascular risk. The study analyzed three indicators of adiposity: body mass index (BMI), waist circumference, and waist-to-height ratio. These measures were examined for association with decline in GFR—defined as eGFR decline of 40% or greater, need for renal replacement therapy, or eGFR less than 10 mL/min/1.73 m2—and with all-cause mortality.

In the general population cohorts, average follow-up was 8 years. During this time, 5.6% of individuals met criteria for GFR decline and 14.7% died. After adjustment for age, sex, race, and smoking, hazard ratios for GFR decline were 1.18 at a BMI of 30, 1.69 at a BMI of 35, and 2.02 at a BMI of 40 (compared to a BMI of 25). The association with BMI was significant for all three criteria for GFR decline. At higher levels of BMI, the associations remained significant after adjustment for other comorbid conditions: HR 1.28 at a BMI of 35 and 1.46 at a BMI of 40. There was a J-shaped relationship between BMI and death, with the lowest risk at a BMI of 25.

Mean follow-up was 4 years in the CKD cohorts and 6 years in the cardiovascular risk cohorts. The associations between BMI and GFR decline were weaker in these risk groups than in the general population cohorts. The J-shaped association with mortality remained, being lowest at BMI between 25 and 30. In the general population, CKD, and cardiovascular risk cohorts, larger waist circumference and higher waist-to-height ratio showed associations with GFR decline similar to that of BMI. The anthropometric measures were not associated with increased mortality, however.

The association between obesity and CKD remains unclear: some studies find no association, while others show a paradoxically lower risk of death. This meta-analysis of individual-level data includes information not only on BMI, but also on measures of central adiposity.

The results show that BMI, waist circumference, and waist-to-height ratio are all independently associated with the risk of GFR decline and death. The associations are significant, although differing in strength, for general population, CKD, and high cardiovascular risk cohorts. The investigators conclude, “These findings suggest that worldwide increases in obesity prevalence could lead to future increases in CKD and ESKD prevalence” [Chang AR, et al. Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium. BMJ 2019; 364: k5301].