Introduction: Uromodulin reflects nephron mass, while urinary neutrophil gelatinase-associated lipocalin (NGAL) indicates kidney injury. We hypothesized that low urinary uromodulin at type 1 diabetes mellitus (T1DM) onset may be linked to acute kidney injury (AKI) and that a higher urinary uromodulin-to-NGAL ratio, reflecting the balance between nephron mass and kidney stress, may reduce the risk of AKI. Our aim was to test these hypotheses. Method: In this prospective study, 75 children (mean age: 8.6 ± 4.3 years) hospitalized for new-onset T1DM were enrolled. AKI was defined as a highest-to-basal serum creatinine ratio ≥1.5. Urinary NGAL and uromodulin levels were measured at admission and upon kidney injury resolution. Results: Of 75 patients, 33 (44%) had diabetic ketoacidosis (11 severe, 10 moderate, 12 mild) and 33 (44%) developed AKI. At T1DM onset, patients with AKI had similar urinary uromodulin levels but higher urinary NGAL levels, higher uromodulin-to-creatinine ratio, and lower urinary uromodulin-to-NGAL ratio than those without AKI. The uromodulin-to-NGAL ratio correlated inversely with the highest-to-basal creatinine ratio (r = −0.42; p < 0.001), while NGAL correlated positively (r = 0.36; p = 0.001). Both urinary NGAL and the uromodulin-to-NGAL ratio at T1DM onset predicted the absence of AKI, with an areas under the receiver-operating characteristic curve of 0.66 (95% confidence interval [CI]: 0.54–0.79; p = 0.01) and 0.75 (95% CI: 0.63–0.86; p < 0.001), respectively. Conclusion: Our findings suggest a potential interplay between nephron mass and kidney stress in AKI development at T1DM onset. While uromodulin levels alone were not associated with AKI, a higher urinary uromodulin-to-NGAL ratio – possibly reflecting better-preserved nephron mass under stress – may be linked to a reduced risk of AKI. Further confirmation is needed.
Acute Kidney Injury at the Onset of Type 1 Diabetes Mellitus: A Balance between Kidney Stress and Nephron Mass
Tirelli P.;Guarino S.;Braile M.;Maisto F.;Iafusco D.;Miraglia del Giudice E.;Cirillo G.;Marzuillo P.
2025
Abstract
Introduction: Uromodulin reflects nephron mass, while urinary neutrophil gelatinase-associated lipocalin (NGAL) indicates kidney injury. We hypothesized that low urinary uromodulin at type 1 diabetes mellitus (T1DM) onset may be linked to acute kidney injury (AKI) and that a higher urinary uromodulin-to-NGAL ratio, reflecting the balance between nephron mass and kidney stress, may reduce the risk of AKI. Our aim was to test these hypotheses. Method: In this prospective study, 75 children (mean age: 8.6 ± 4.3 years) hospitalized for new-onset T1DM were enrolled. AKI was defined as a highest-to-basal serum creatinine ratio ≥1.5. Urinary NGAL and uromodulin levels were measured at admission and upon kidney injury resolution. Results: Of 75 patients, 33 (44%) had diabetic ketoacidosis (11 severe, 10 moderate, 12 mild) and 33 (44%) developed AKI. At T1DM onset, patients with AKI had similar urinary uromodulin levels but higher urinary NGAL levels, higher uromodulin-to-creatinine ratio, and lower urinary uromodulin-to-NGAL ratio than those without AKI. The uromodulin-to-NGAL ratio correlated inversely with the highest-to-basal creatinine ratio (r = −0.42; p < 0.001), while NGAL correlated positively (r = 0.36; p = 0.001). Both urinary NGAL and the uromodulin-to-NGAL ratio at T1DM onset predicted the absence of AKI, with an areas under the receiver-operating characteristic curve of 0.66 (95% confidence interval [CI]: 0.54–0.79; p = 0.01) and 0.75 (95% CI: 0.63–0.86; p < 0.001), respectively. Conclusion: Our findings suggest a potential interplay between nephron mass and kidney stress in AKI development at T1DM onset. While uromodulin levels alone were not associated with AKI, a higher urinary uromodulin-to-NGAL ratio – possibly reflecting better-preserved nephron mass under stress – may be linked to a reduced risk of AKI. Further confirmation is needed.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
