Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease

Background: Ubiquitin-52 amino acid fusion protein (UbA52) is an important factor in the pathogenesis of diabetic kidney disease (DKD) and has been suggested a potential marker in the disease. However, whether upregulation of UbA52 marks early kidney injury in T2DM mellitus (T2DM) patients remains u...

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Main Authors: Xiaochang Xu, Yejing Dong, Maodong Liu, Ying Li, Yimin Zhang
Format: Article
Language:English
Published: Elsevier 2021-09-01
Series:Nefrología (English Edition)
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2013251421001164
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author Xiaochang Xu
Yejing Dong
Maodong Liu
Ying Li
Yimin Zhang
author_facet Xiaochang Xu
Yejing Dong
Maodong Liu
Ying Li
Yimin Zhang
author_sort Xiaochang Xu
collection DOAJ
description Background: Ubiquitin-52 amino acid fusion protein (UbA52) is an important factor in the pathogenesis of diabetic kidney disease (DKD) and has been suggested a potential marker in the disease. However, whether upregulation of UbA52 marks early kidney injury in T2DM mellitus (T2DM) patients remains unclear. In this study, we examine the diagnostic value of UbA52 as a biomarker in predicting early diabetic kidney disease (DKD) in T2DM patients. Methods: We used two-step ELISA to test UbA52 level in urine of 3 defined patient groups. Samples from T2DM patients without albuminuria or diabetic retinopathy (DM-WNP; n = 30), T2DM patients with albuminuria and diabetic retinopathy, excluding other renal diseases clinically (DM-NP; n = 30) and healthy controls (n = 30) were analyzed. Spearman's correlation analysis and multiple linear regression model were used to analyze the correlation of urinary UbA52 level with laboratory results regarding kidney function. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of UbA52 in predicting T2DM and early DKD. Results: Urinary UbA52 level in DM-NP group was 1.75 times and 2.71 times higher than in DN-WNP (p = 0.004) and normal control group (p < 0.001), respectively. The level of urinary UbA52 correlated significantly with serum creatinine (r = 0.468, p < 0.001), GFR (r = −0.300, p = 0.004) and proteinuria (r = 0.484, p < 0.001). Multiple linear regression analysis showed that proteinuria level was independently associated with urinary UbA52 level (β = 0.833, p < 0.001). The area under the ROC of urinary UbA52 in diagnosing T2DM and DKD was 0.751 and 0.755, respectively. Conclusion: The level of urinary UbA52 increased significantly in T2DM patients with DKD. The level of proteinuria is independently associated with urinary UbA52 level. Urinary UbA52 could serve as an early marker in the diagnosis of DKD.ClinicalTrials.gov Identifier: NCT02204280. Resumen: Antecedentes: La proteína de fusión de aminoácidos ubiquitina-52 (UbA52) es un factor importante en la patogénesis de la enfermedad renal diabética (ERD), y se ha sugerido como marcador potencial en la enfermedad. Sin embargo, aún no está claro si la regulación al alza de UbA52 indica una lesión renal temprana en pacientes con diabetes mellitus de tipo 2 (DMT2). En este estudio, analizamos el valor diagnóstico de UbA52 como biomarcador para predecir la ERD temprana en pacientes con DMT2. Métodos: Utilizamos un ELISA de 2 pasos para analizar el nivel de UbA52 en la orina de 3 grupos de pacientes definidos. Se analizaron muestras de pacientes con DMT2 sin albuminuria o retinopatía diabética (DM-WNP; n = 30), pacientes con DMT2 y con albuminuria y retinopatía diabética, excluyendo clínicamente otras enfermedades renales (DM-NP; n = 30) y controles sanos (n = 30). Se utilizó el análisis de correlación de Spearman y el modelo de regresión lineal múltiple para analizar la correlación del nivel de UbA52 en orina con los resultados de laboratorio relativos a la función renal. Se utilizó la curva de características operativas del receptor (ROC) para evaluar el valor diagnóstico de UbA52 en la predicción de la DMT2 y de la ERD temprana. Resultados: El nivel de UbA52 en orina en el grupo DM-NP fue 1,75 y 2,71 veces mayor que en el grupo DN-WNP (p = 0,004), y en el grupo de control normal (p < 0,001), respectivamente. El nivel de UbA52 en orina se correlacionó significativamente con la creatinina sérica (r = 0,468; p < 0,001), la TFG (r = −0,300; p = 0,004) y la proteinuria (r = 0,484; p < 0,001). El análisis de regresión lineal múltiple mostró que el nivel de proteinuria se asociaba de forma independiente al nivel de UbA52 en orina (β = 0,833; p < 0,001). El área bajo las ROC de UbA52 en orina en el diagnóstico de la DMT2 y de la ERD fue de 0,751 y 0,755, respectivamente. Conclusión: El nivel de UbA52 en orina aumentó significativamente en pacientes con DMT2 y ERD. El nivel de proteinuria se asocia independientemente al nivel de UbA52 en orina. UbA52 en orina podría servir como marcador temprano en el diagnóstico de la ERD.
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spelling doaj.art-a7ec06f1a3234f77be10f05f0a2510ad2022-12-21T19:38:38ZengElsevierNefrología (English Edition)2013-25142021-09-01415548555Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney diseaseXiaochang Xu0Yejing Dong1Maodong Liu2Ying Li3Yimin Zhang4Division of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDivision of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDivision of Nephrology, The Third Affiliated Hospital, Hebei Medical University, Shijiazhuang, ChinaDivision of Nephrology, The Third Affiliated Hospital, Hebei Medical University, Shijiazhuang, ChinaDivision of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Corresponding author.Background: Ubiquitin-52 amino acid fusion protein (UbA52) is an important factor in the pathogenesis of diabetic kidney disease (DKD) and has been suggested a potential marker in the disease. However, whether upregulation of UbA52 marks early kidney injury in T2DM mellitus (T2DM) patients remains unclear. In this study, we examine the diagnostic value of UbA52 as a biomarker in predicting early diabetic kidney disease (DKD) in T2DM patients. Methods: We used two-step ELISA to test UbA52 level in urine of 3 defined patient groups. Samples from T2DM patients without albuminuria or diabetic retinopathy (DM-WNP; n = 30), T2DM patients with albuminuria and diabetic retinopathy, excluding other renal diseases clinically (DM-NP; n = 30) and healthy controls (n = 30) were analyzed. Spearman's correlation analysis and multiple linear regression model were used to analyze the correlation of urinary UbA52 level with laboratory results regarding kidney function. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of UbA52 in predicting T2DM and early DKD. Results: Urinary UbA52 level in DM-NP group was 1.75 times and 2.71 times higher than in DN-WNP (p = 0.004) and normal control group (p < 0.001), respectively. The level of urinary UbA52 correlated significantly with serum creatinine (r = 0.468, p < 0.001), GFR (r = −0.300, p = 0.004) and proteinuria (r = 0.484, p < 0.001). Multiple linear regression analysis showed that proteinuria level was independently associated with urinary UbA52 level (β = 0.833, p < 0.001). The area under the ROC of urinary UbA52 in diagnosing T2DM and DKD was 0.751 and 0.755, respectively. Conclusion: The level of urinary UbA52 increased significantly in T2DM patients with DKD. The level of proteinuria is independently associated with urinary UbA52 level. Urinary UbA52 could serve as an early marker in the diagnosis of DKD.ClinicalTrials.gov Identifier: NCT02204280. Resumen: Antecedentes: La proteína de fusión de aminoácidos ubiquitina-52 (UbA52) es un factor importante en la patogénesis de la enfermedad renal diabética (ERD), y se ha sugerido como marcador potencial en la enfermedad. Sin embargo, aún no está claro si la regulación al alza de UbA52 indica una lesión renal temprana en pacientes con diabetes mellitus de tipo 2 (DMT2). En este estudio, analizamos el valor diagnóstico de UbA52 como biomarcador para predecir la ERD temprana en pacientes con DMT2. Métodos: Utilizamos un ELISA de 2 pasos para analizar el nivel de UbA52 en la orina de 3 grupos de pacientes definidos. Se analizaron muestras de pacientes con DMT2 sin albuminuria o retinopatía diabética (DM-WNP; n = 30), pacientes con DMT2 y con albuminuria y retinopatía diabética, excluyendo clínicamente otras enfermedades renales (DM-NP; n = 30) y controles sanos (n = 30). Se utilizó el análisis de correlación de Spearman y el modelo de regresión lineal múltiple para analizar la correlación del nivel de UbA52 en orina con los resultados de laboratorio relativos a la función renal. Se utilizó la curva de características operativas del receptor (ROC) para evaluar el valor diagnóstico de UbA52 en la predicción de la DMT2 y de la ERD temprana. Resultados: El nivel de UbA52 en orina en el grupo DM-NP fue 1,75 y 2,71 veces mayor que en el grupo DN-WNP (p = 0,004), y en el grupo de control normal (p < 0,001), respectivamente. El nivel de UbA52 en orina se correlacionó significativamente con la creatinina sérica (r = 0,468; p < 0,001), la TFG (r = −0,300; p = 0,004) y la proteinuria (r = 0,484; p < 0,001). El análisis de regresión lineal múltiple mostró que el nivel de proteinuria se asociaba de forma independiente al nivel de UbA52 en orina (β = 0,833; p < 0,001). El área bajo las ROC de UbA52 en orina en el diagnóstico de la DMT2 y de la ERD fue de 0,751 y 0,755, respectivamente. Conclusión: El nivel de UbA52 en orina aumentó significativamente en pacientes con DMT2 y ERD. El nivel de proteinuria se asocia independientemente al nivel de UbA52 en orina. UbA52 en orina podría servir como marcador temprano en el diagnóstico de la ERD.http://www.sciencedirect.com/science/article/pii/S2013251421001164Enfermedad renal diabéticaUbA52OrinaBiomarcadoresDiagnóstico
spellingShingle Xiaochang Xu
Yejing Dong
Maodong Liu
Ying Li
Yimin Zhang
Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease
Nefrología (English Edition)
Enfermedad renal diabética
UbA52
Orina
Biomarcadores
Diagnóstico
title Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease
title_full Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease
title_fullStr Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease
title_full_unstemmed Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease
title_short Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease
title_sort clinical significance of uba52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease
topic Enfermedad renal diabética
UbA52
Orina
Biomarcadores
Diagnóstico
url http://www.sciencedirect.com/science/article/pii/S2013251421001164
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