Birth Weight Is Associated With Kidney Size in Middle-Aged Women

Abstract

Introduction: Low birth weight (LBW) is associated with increased risk of kidney disease due to lower nephron endowment leading to hyperfiltration and subsequent nephron loss. Kidney size is commonly used as a proxy for nephron number. We compared kidney volume measured by magnetic resonance imaging (MRI) with measured glomerular filtration rate (mGFR) in adults with either normal birth weight (NBW) or low birth weight (LBW).

Methods: Healthy individuals aged 42 to 52 years with LBW (1100-2300 g) and NBW (3500 -4000 g) were invited to participate. The GFR was measured using plasma clearance of iohexol. Kidney volume was measured on magnetic resonance images using axial T2 images and coronal T1 images with fat saturation without contrast enhancement; calculations were performed according to the ellipsoid formula π/6 × length × width × depth.

Results: We included 102 individuals (54 LBW and 48 NBW). Total kidney volume was 302 ± 51 ml for female NBW vs 258 ± 48 ml for female LBW individuals (P = 0.002). For male individuals, total kidney volume was 347 ± 51 ml vs. 340 ± 65 ml (P = 0.7). The mGFR was significantly associated with kidney volume, with r = 0.52 (P < 0.001) for women and r = 0.39 (P = 0.007) for men. A mediation analysis showed that the association between birth weight and mGFR (significant in total sample and women) was mediated by kidney volume.

Conclusion: Healthy female individuals born with LBW have smaller kidneys than healthy females born with NBW. The previously shown associations between LBW and lower mGFR in adult women might be explained by smaller kidney volume.

Keywords: kidney size; low birth weight; magnetic resonance imaging; ultrasonography.

Graphical abstract

Figure 1

Distribution of kidney volume comparing low birth weight (LBW) and normal birth weight (NBW). Boxplot showing distribution of kidney volume stratified for sex and birth weight group. Sex-stratified comparison between birth weight groups was done using the Student t test, and P value is shown.

Figure 2

Relationship between kidney volume and measured glomerular filtration rate (GFR). Sex-stratified regression lines between kidney volume and measured GFR shown in pink (female) and blue (male). Sex-stratified correlation coefficient (Pearson r) and P value are shown.

Figure 3

Kidney volume mediates effect of birth weight on measured glomerular filtration rate (GFR). (a) Example model, (b) total sample, (c) female individuals only, and (d) male individuals only. Each figure represents 3 regression equations: (i) independent variable → dependent variable, β1 is the effect estimate (with 95% confidence interval); (ii) independent variable → mediator, with β2 as the effect estimate; and iii) independent variable and mediator → dependent variable, with β3 as the effect estimate of the mediator and β4 as the effect estimate of the independent variable. The direct effect of the independent variable is the same as β4, whereas the indirect (mediated) effect, is β2 ∗ β3 or also β4 – β1. As shown in the figure, the effect of birth weight on measured GFR (significant β1 in women and total sample) was in fact mediated by the kidney volume (indirect effect).