Birth Weight: A Predictive Medicine Consideration for the Disparities in CKD

Chronic kidney disease (CKD) represents a major public health concern throughout the world.1 In addition to the health burden, the costs of treatment continue to increase in nearly all populations around the world, such that the economic burden is nearing a critical point for global health care.2 Moreover, significant racial and ethnic disparities are evident along with the increasing disease burden from CKD for the entire population.2 For example, African Americans and Native Americans have significantly greater rates of kidney failure, as well as earlier onset and progression of disease, than whites.2 These trends are consistent with the prevalence of traditional kidney disease risk factors, as well as variations in control of glycemia, high blood pressure, and dyslipidemia. However, although a substantial proportion of CKD risk, in addition to the racial disparities in disease rates, is associated with increased blood pressure and diabetes, these parameters do not fully explain the excess of kidney disease in ethnic minorities or accurately identify individuals at greatest risk.3, 4, 5 Identification of predictive factors before the development of macrovascular and microvascular disease is a critical issue for the assessment of kidney disease risk. In other diseases of adulthood, such as stroke, birth place has been associated with increased population risk, and early-life factors have been proposed as contributing to these risk levels.6, 7

More than 2 decades ago, Barker and Osmond8 introduced the fetal origins of adult disease hypothesis, which identified fetal and early-life events associated with increased chronic disease risks later in life. Low birth weight, as an indicator of uterine restriction, and malnutrition and organ underdevelopment are a common parameter and measure for the Barker hypothesis.8 The fetal origins of adult disease area of study has identified excess risks for numerous conditions and disorders that manifest later in life. The contribution of intrauterine risk factors to CKD is logical and reasonable given the extensive evidence in the literature regarding the effects of fetal malnutrition on the early development of the kidney. Bagby9 has described the pathways of the developmental origins of adult kidney disease from multiple components, including maternal nutrition, low nephron number, and blood pressure level.

In this issue of the American Journal of Kidney Diseases, White et al10 present results of a systematic review of observational studies regarding size at birth and CKD, identifying lower birth weight as associated with increased risk of decreased kidney function and kidney failure. These investigators assessed 31 cohort and case-control studies that included birth weight and markers of kidney disease. Significant associations were identified between birth weight and albuminuria, low estimated glomerular filtration rate, and treatment of kidney failure by means of dialysis and transplantation. This assessment included a diverse set of study populations with different racial and ethnic groups.

Figure 1 shows low-birth-weight rates, defined as birth weight less than 2,500 g, for 1974 to 2006 for whites and African Americans. These rates were based on live births from South Carolina vital records. African Americans have a 2-fold greater risk of smaller babies weighing less than 2,500 g compared with white babies. In 2006, a total of 14.8% of African American births were low birth weight compared with 7.6% of white births. Rates of low birth weight increased from 1974 to 2006, with a 12.1% increase for African Americans and a 16.9% increase for whites. The racial disparities and greater low-birth-weight rates for African Americans are consistent with their greater risk of CKD. With the increasing rates and numbers of low-birth-weight individuals, risks of CKD might be expected to continue to increase in future generations.

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Figure 1. Trends in low-birth-weight (<2,500 g) rates per 100 births by race (white and African American) from 1974 to 2006 in South Carolina. During the study period, African Americans maintained rates nearly 2-times greater than whites. Rates of low birth weights are increasing in all births regardless of race.

Although the studies included in the systematic review by White et al10 identify a consistent association between CKD and low birth weight, considerable work remains to be done in this area. First, the potential increase in kidney disease risk suggested by this analysis warrants continued assessment of the mechanisms associated with fetal and early-life events.11, 12 The different stages of kidney disease (albuminuria, low glomerular filtration rate, and treated kidney failure) were each associated with low birth weight; however, the mechanisms could be different.13, 14 For example, in a study of the relation between birth weight and medication used to treat hypertension, low birth weight was associated with different classes of therapy in both white and African American patients with hypertension, suggesting different mechanisms of action in the fetal origins of high blood pressure.13 Assessment of birth weight and CKD is complicated further by the different pathways of risks. Because low birth weight was associated with different stages of kidney disease in this report, significant associations were reported with both hypertension and diabetic kidney disease, as well as with other and unknown causes.14, 15, 16 However, hypertension and diabetes also are associated with low birth weight and progression of CKD. This complicates assessment of biological pathways.17, 18, 19

CKD represents a major public health challenge for the future. The increasing trend and racial disparities in prevalence indicate the need for predictive models that can identify factors most likely to be amenable to intervention. Fetal and early-life events have been associated with increased kidney disease risks. This provides a basis for the design and development of targeted interventional strategies.