Latent Intrarenal Renin-Angiotensin-Aldosterone System Activation Could Persist Until Early School-Aged in Children with a History of Low Birth Weight.

BACKGROUND

The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in kidney development and the progression of chronic kidney disease (CKD).

OBJECTIVES

To identify children with low birth weight (LBW) at risk of CKD who have RAAS activation.

DESIGN

We conducted a prospective cohort study to evaluate whether a history of LBW contributes to the development of latent RAAS activation using urine samples from patients with short stature with no clinical kidney symptoms. Additionally, among children who had idiopathic nephrotic syndrome (INS), we examined how a history of LBW contributes to the development of latent RAAS activation using residual kidney biopsy samples.

METHODS

We prospectively evaluated angiotensinogen (AGT) using spot urine in children with and without a history of LBW, who required evaluation for short stature without kidney symptoms at registration. We also performed immunohistochemical staining of AGT using kidney biopsy specimens of subjects with and without a history of LBW who had INS. Urinary AGT was assessed as a marker of intrarenal RAAS.

RESULTS

In 45 children (median age 5 years), urinary AGT/creatinine (Cr) levels were significantly higher in children with a history of LBW (n = 24) than in those without (n = 21, median: 12.6 vs 6.7 µg/g･Cr, mean: 15.4 vs 9.1 µg/g･Cr, P < .01). The unadjusted mean difference between the 2 groups and the 95% confidence interval were 6.3 and (1.6, 11.1), respectively. In the immunohistochemical kidney pathological study, the positive area of AGT staining in the kidney tubules of 3 subjects with a history of LBW was more extensive than that of 3 additional subjects without a history of LBW.

CONCLUSION

Our results indicated that latent intrarenal RAAS activation in children with a history of LBW persists until early school age and may contribute to the progression of CKD.