Serum Uromodulin in Children and Adolescents with Type 1 Diabetes Mellitus and Controls: Its Potential Role in Kidney Health.

INTRODUCTION: Uromodulin is a kidney-specific tubular protein, and its assessment in serum (sUMOD) reveals the potential as a novel marker for function and the integrity of renal parenchymal cells and does not directly depend on the glomerular filtration rate. Early diabetic nephropathy parallels glomerular hyperfiltration, often leading to diagnostic misinterpretation. Moreover, traditional kidney function markers are not able to diagnose structural lesions. Recent data show that sUMOD is linked to glucose intolerance in adults. Thus, we launched to assess the hypothesis that sUMOD is also associated with kidney function, biometric data, and quality of metabolic control in children/adolescents with type 1 diabetes. PATIENTS AND METHODS: Patients with type 1 diabetes (n=135) and healthy controls (n=69) were recruited to participate in the trial. Clinical, biometrical data, sUMOD, and other laboratory parameters were assessed. RESULTS: The mean concentrations of sUMOD in diabetic patients and controls were comparable (201.19±103.22 vs. 198.32±84.27 ng/mL, p=0.832). However, in contrast to healthy controls, sUMOD levels in patients with diabetes were associated with serum-creatinine (r=-0.368, p<0.0001), age (r=-0.350, p<0.0001), height (r=-0.379, p<0.0001), body weight (r=-0.394, p<0.0001), Body mass index (r=-0.292, p=0.001), daily insulin dosage (r=-0.300, p<0.0001), HbA1c (%) (r=-0.190, p=0.027), standardized HbA1c/IFCC (mmol/mol) (r=-0.189, p=0.028), and systolic (r=-0.299, p<0.0001) and diastolic (r=-0.235, p=0.006) arterial blood pressure. CONCLUSIONS: Our study shows that children/adolescents with type 1 diabetes disclose similar sUMOD concentrations as healthy controls. Serum UMOD appears to indicate higher risks for kidney tissue remodeling and possibly subsequent cardiovascular alterations. However, further studies are mandatory to settle these findings.

A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse.

Congenital heart diseases (CHDs) are major causes of infant death in the United States. In the 1980s and earlier, most patients with moderate or severe CHD died before adulthood, with the maximum mortality during the first week of life. Remarkable advances in surgical techniques, diagnostic approaches, and medical management have led to marked improvements in outcomes. To address the critical research needs of understanding congenital heart defects, murine models have provided an ideal research platform, as they have very similar heart anatomy to humans and short gestation rates. The combination of genetic engineering with high-throughput phenotyping tools has allowed for the replication and diagnosis of structural heart defects to further elucidate the molecular pathways behind CHDs. The use of noninvasive fetal echocardiography to screen the cardiac phenotypes in mouse models coupled with the high fidelity of Episcopic fluorescence image capture (EFIC) using Episcopic confocal microscopy (ECM) histopathology with three-dimensional (3D) reconstructions enables a detailed view into the anatomy of various congenital heart defects. This protocol outlines a complete workflow of these methods to obtain an accurate diagnosis of murine congenital heart defects. Applying this phenotyping protocol to model organisms will allow for accurate CHD diagnosis, yielding insights into the mechanisms of CHD. Identifying the underlying mechanisms of CHD provide opportunities for potential therapies and interventions.