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

Abstract

Uromodulin is a kidney specific tubular protein and, since recently assessed in serum (sUMOD), reveals potential as a novel marker for both function and the integrity of renal parenchymal cells, and not directly depending on the glomerular filtration rate. Early diabetic nephropathy parallels glomerular hyperfiltration, often leading to diagnostic misinterpretation. Moreover, traditional kidney function markers are unsuitable 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, biometrical data and quality of metabolic control in children/adolescents with type 1 diabetes. Patients and methods 135 patients with type 1 diabetes and 69 healthy controls were recruited to participate in the trial. Clinical, biometrical data and sUMOD together with various 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), BMI (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), 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 maybe consecutively cardiovascular alterations. However, further studies are mandatory to settle these findings.

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

“…PLG (plasminogen) [73], AFM (afamin) [54], AGTR1 [74] and UMOD (uromodulin) [75] might be a potential therapeutic target for sepsis. Abnormal regulation of PLG (plasminogen) [76], AFM (afamin) [77], GSTA1 [78], AGTR1 [79] and UMOD (uromodulin) [80] are associated with diabetes mellitus. PLG (plasminogen) [81] plays an indispensable role in glomerulonephritis.…”

Selected Serum Markers Associated with Pathogenesis and Clinical Course of Type 1 Diabetes in Pediatric Patients—The Effect of Disease Duration

“…In a number of studies, selected biologically active substances were indicated as contributing to the etiology (IAPP [ 16 , 31 , 32 , 33 , 34 , 35 , 36 ], proIAPP [ 17 , 18 , 37 ], I-FABP [ 24 ]), course (CST [ 38 , 39 ], ChgA [ 40 , 41 , 42 ]) or the development of various complications (neuropathy—NGF [ 43 , 44 , 45 ], cardiovascular complications—PAF [ 26 , 46 , 47 ], and cardiovascular complications and nephropatia—UMOD [ 28 , 48 , 49 ]). In the current study, we assessed the diagnostic usefulness of these indicators present in T1D patients’ sera and confirmed statistically significant differences between their concentrations in the group of children with T1D and healthy children, but only some of them (NGF, ChgA, CST and PAF) were affected by disease duration.…”

“…We also included in our analysis substances potentially evaluable as indicators of late complications, neurological—nerve growth factor (NGF) [ 25 ], and vascular—platelet-activating factor (PAF) [ 26 , 27 ]. Finally, we assessed uromodulin, a protein secreted by the cells of the distal nephron tubules, strongly correlated with eGFR, which could be related to diabetic nephropathy in T1D patients [ 28 ].…”

Unveiling the Hidden Power of Uromodulin: A Promising Potential Biomarker for Kidney Diseases

“…Children/adolescents with type 1 diabetes exhibit serum uromodulin concentrations comparable to those of healthy controls [168]. Conversely, Wiromrat et al reported reduced serum uromodulin concentrations in adolescents with type 1 diabetes compared with their non-diabetic counterparts.…”

“…Serum uromodulin levels seem to be associated with an increased risk of kidney tissue remodeling and potentially subsequent cardiovascular changes [168]. In type 1 diabetes, there is a pressing need for novel biomarkers that can more accurately predict coronary artery calcification (CAC), an indicator of subclinical atherosclerosis and DKD.…”