Tirelli Paola, Guarino Stefano, Braile Mariantonia, Maisto Francesca, Iafusco Dario, Zanfardino Angela, Di Sessa Anna, Miraglia Del Giudice Emanuele, Cirillo Grazia, Marzuillo Pierluigi
Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
Horm Res Paediatr. 2025 Jun 21:1-6. doi: 10.1159/000547090.
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.
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.
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.
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.
尿调节蛋白反映肾单位数量,而尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)提示肾损伤。我们推测,1型糖尿病(T1DM)发病时尿调节蛋白水平低可能与急性肾损伤(AKI)有关,且尿调节蛋白与NGAL的比值更高,反映了肾单位数量与肾应激之间的平衡,可能会降低AKI的风险。我们的目的是验证这些假设。
在这项前瞻性研究中,纳入了75名因新发T1DM住院的儿童(平均年龄:8.6±4.3岁)。AKI定义为最高血清肌酐与基础血清肌酐之比≥1.5。在入院时和肾损伤缓解时测量尿NGAL和尿调节蛋白水平。
75例患者中,33例(44%)患有糖尿病酮症酸中毒(11例重度、10例中度、12例轻度),33例(44%)发生AKI。在T1DM发病时,与未发生AKI的患者相比,发生AKI的患者尿调节蛋白水平相似,但尿NGAL水平更高、尿调节蛋白与肌酐比值更高、尿调节蛋白与NGAL比值更低。尿调节蛋白与NGAL的比值与最高血清肌酐与基础血清肌酐之比呈负相关(r = -0.42;p < 0.001),而NGAL呈正相关(r = 0.36;p = 0.001)。T1DM发病时的尿NGAL和尿调节蛋白与NGAL的比值均预测未发生AKI,受试者工作特征曲线下面积分别为0.66(95%置信区间[CI]:0.54 - 0.79;p = 0.01)和0.75(95%CI:0.63 - 0.86;p < 0.001)。
我们的研究结果提示,在T1DM发病时AKI的发生过程中,肾单位数量与肾应激之间可能存在相互作用。虽然单独的尿调节蛋白水平与AKI无关,但尿调节蛋白与NGAL的比值更高——可能反映了在应激状态下肾单位数量保存得更好——可能与AKI风险降低有关。需要进一步证实。