Latent intrarenal renin-angiotensin-aldosterone system activation could persist until toddlerhood in children with a history of low birth weight

Purpose The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in kidney development and the progression of chronic kidney disease (CKD). However, no studies have examined the association between RAAS and CKD in children with a history of preterm birth and low birth weight (LBW). Methods In first urine biomarker study, we prospectively evaluated intrarenal RAAS markers using spot urine in children, both with and without a history of LBW, who required evaluation for short stature and had no clinical kidney symptoms at registration. In second, we conducted a retrospective immunohistochemical pathological study using kidney biopsy specimens in subjects, both with and without a history of LBW, with reduced kidney function and pathological glomerular hypertrophy. Urinary angiotensinogen (AGT) was assessed as a marker of intrarenal RAAS. Results A total of 45 children with a median age of 5.0 years were evaluated in the prospective biomarker study. Urinary AGT/creatinine (Cr) levels were significantly higher in children with a history of LBW (n = 24) than in those without (n = 21; 12.6 vs. 6.7 µg/ng Cr, p  < 0.01). In the immunohistochemical kidney pathological study, the positive area of AGT staining in the renal tubules of the subject with a history of LBW was more extensive than that of the subject without a history of LBW. Conclusions Our biomarker and pathological studies indicated that latent intrarenal RAAS activation in children with a history of LBW persists until toddlerhood and may contribute to the progression of CKD.