Evaluation of kidney injury and metabolomic analysis in adulthood in a non-obese hyperglycemic mouse model after birth with low birthweight

Background Low birthweight infants have high risk of developing chronic kidney disease (CKD) in later in life, however, the pathogenesis of this disease remains unclear. This study aimed to investigate the underlying mechanism using a low birthweight-non-obese hyperglycemic adulthood mouse model. Methods Pregnant ICR-strain mice underwent uterine artery ligation at day 16.5 of gestation to induce fetal hypoxia (ischemic group, I). Female newborns were weaned at 4 weeks of age and fed a normal diet until 8 weeks of age (n = 10). The group I was compared to the control group (C) regarding the body weight, tubular injury markers, renal function, pathology, and metabolome analysis. Results Group I were born with a low birth weight (group I: C = 1.4:1.9 g, p < 0.01), which persisted after birth. By 8 weeks of age, there were minimal changes in kidney histopathology between the two groups. However, group I showed an increase in markers for detection of CKD, such as urinary β2-microglobulin levels (group I༚C = 116:26 µg/L), albumin levels (group I༚C=0.14:0.07 mg/gCr) (both p < 0.01) and serum creatinine levels (group I༚C༝0.18:0.12 mg/dL, p < 0.05). Furthermore, kidney metabolomic analysis revealed notable differences between the two groups, particularly in succinic acid, S-adenosylmethionine, and N1-methyl-4-pyridone-5-carboxamide (4PY), which are closely linked to kidney injury. Conclusion The low birthweight-non-obese hyperglycemic mouse model may develop CKD in adulthood, potentially caused by increased renin activity related to succinic acid and tissue injury related to S-adenosylmethionine and 4PY.