RM. Matter, DE. Sallam, SI. Taha, SM. Awadallah, R. Khamees and NY. Salah (2025). Transient renal tubular injury among children and adolescents during diabetic ketoacidosis: severity, renal perfusion, and urinary netrin- 1 interplay. European journal of pediatrics, 184(6), 329. https://doi.org/10.1007/s00431-025-06145-1

PubMed 40332546

[Abstract]
UNLABELLED: Acute kidney injury (AKI) has been reported during diabetic ketoacidosis (DKA). Evidence regarding tubulopathy is less established, with its pathophysiology, risk determinants, and short-term outcome to be unraveled. Hence, this study aimed to assess renal tubular functions during DKA, its short-term outcome, and its relation with urinary Netrin-1, DKA severity, and renal perfusion indices. Forty children and adolescents (20 with moderate and 20 with severe DKA) were assessed for urine output (UOP), blood pressure, blood glucose, HbA1c, and urinary Netrin-1, with calculation of serum osmolality and estimated glomerular filtration rate (eGFR). Renal pulsatility and resistivity indices were assessed by renal duplex. Reevaluation was done on days 3 and 14. Sixteen children and adolescents had tubular proteinuria during DKA (40%). Their mean urine output (UOP) during DKA was 14.03 cc/kg/h, and their mean urinary Netrin-1 was 836.9 ng/ml. A significant improvement was observed in the UOP, protein/creatinine ratio, urinary netrin, and serum osmolality after the resolution of DKA accompanied by a significant decrease in renal resistivity and pulsatility indices (p < 0.05). A significant positive correlation was found between tubular proteinuria during DKA and urinary Netrin-1, renal pulsatility, and resistivity indices (p < 0.05). Multivariate regression analysis revealed that serum PH and urinary Netrin-1 were the most significant independent variables associated with tubular proteinuria among children and adolescents during DKA.

CONCLUSION: Transient renal tubulopathy occurs during DKA manifested by tubular proteinuria, polyuria, and hypokalemia; that is correlated with DKA severity, renal perfusion indices, and urinary Netrin-1 and reversible by day 14 post-DKA. Netrin-1 could serve as a potential therapeutic target for DKA-associated tubulopathy.

WHAT IS KNOWN: • Diabetic ketoacidosis (DKA) is a severe acute complication of diabetes mellitus, with negative effect on multiple body organs. • Studies increasingly suggest acute kidney injury during DKA, however, data about renal tubular injury during DKA, it's pathophysiology, risk determinants and short term outcomes are still unclear.

WHAT IS NEW: • Transient renal tubulopathy was reported in 40 % the studied children and adolescents during DKA manifested by proteinuria, polyurea, and hypokalemia. • This tubulopathy that was correlated with DKA severity, renal perfusion indices and urinary Netrin-1 and totally reversible by day 14 post DKA.