Elevated urinary IL-36α and IL-18 levels are associated with diabetic nephropathy in patients with type 2 diabetes mellitus

Chakraborty, Rajarshi; Parveen, Rizwana; Varshney, Prabhat; Kapur, Prem; Khatoon, Saima; Saha, Nilanjan; Agarwal, Nidhi

doi:10.23736/s2724-6507.20.03196-x

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…In DKD progression, some blood and urine biomarkers might directly reflect the disease condition and were proven to be good predictors. [26][27][28][29][30] In the present study, our results showed that urinary NAG/CR levels exhibited remarkable difference between early and advanced DKD, and patient with advanced DKD was more likely to have higher levels of NAG/CR than that with early DKD. Our findings indicated that NAG/CR is closely associated with the severity of DKD, and may probably be a powerful risk predictor for advanced DKD, which suggests that the measurement of urinary NAG/ CR level will be helpful to evaluate the condition and progression of DKD.…”

Section: Discussionsupporting

confidence: 55%

“…In the different stages of DKD, patients may demonstrate different clinical features consistent with the severity of the disease. In DKD progression, some blood and urine biomarkers might directly reflect the disease condition and were proven to be good predictors 26–30 . In the present study, our results showed that urinary NAG/CR levels exhibited remarkable difference between early and advanced DKD, and patient with advanced DKD was more likely to have higher levels of NAG/CR than that with early DKD.…”

Section: Discussionsupporting

confidence: 53%

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Urinary N‐acetyl‐β‐d‐glucosaminidase‐creatine ratio is a valuable predictor for advanced diabetic kidney disease

Huang

Fei

Zhan

et al. 2022

Clinical Laboratory Analysis

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Background: Many biomarkers show high diagnostic values for diabetic kidney disease (DKD), but fewer studies focus on the predictive assessment of DKD progression by blood and urinary biomarkers.Aim: This study aims to find powerful risk predictors and identifying biomarkers in blood and urine for DKD progression.Methods: A total of 117 patients with type 2 DKD including early and advanced stages and their laboratory parameters were statistically assessed. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the significance of discriminating between early and advanced DKD, and the predictive power for advanced DKD was analyzed by regression analysis and trisector grouping.Results: N-acetylβd-glucosaminidase-creatine (NAG/CR) level in advanced DKD was statistically higher than that in early DKD (p < 0.05), and there was a higher incidence of advanced DKD (72% vs. 56%) and high odds ratio (OR: 3.917, 95% CI: 1.579-10.011) of NAG/CR with ≥2.79 U/mmol compared with <2.79 U/mmol (p < 0.05).NAG/CR ratio also showed a higher area under the ROC curve of 0.727 (95% CI: 0.616-0.828, p = 0.010) with a high sensitivity (0.75) and a moderate specificity (0.66) when 1.93 U/mmol was set as the optimal cutoff value. The adjusted-multivariable analysis revealed that NAG/CR had an OR of 1.021 (95% CI: 1.024-1.038) and 2.223 (95% CI: 1.231-4.463) based on a continuous and categorical variable, respectively, for risk of advanced DKD. Moreover, the prevalence of advanced DKD exhibited an increasing tendency by an increment of the trisector of NAG/CR. How to cite this article: Huang Q, Fei X, Zhan H, et al. Urinary N-acetylβd-glucosaminidase-creatine ratio is a valuable predictor for advanced diabetic kidney disease.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionsupporting

confidence: 53%

Urinary N‐acetyl‐β‐d‐glucosaminidase‐creatine ratio is a valuable predictor for advanced diabetic kidney disease

Huang

Fei

Zhan

et al. 2022

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

“…In development and progression of T2D and DKD, some basic biomarkers in blood and urine may directly demonstrate the status of disease, and are sure to be good predictors [27][28][29][30]. In this study, when using plasma FIB and urinary α1-MG/CR as well as their combination as predictive factors, their optimal cut-off points would be needed to categorize patients with and without the risk.…”

Section: Discussionmentioning

confidence: 98%

Predictive significance of joint plasma fibrinogen and urinary alpha-1 microglobulin-creatinine ratio in patients with diabetic kidney disease

Pan¹,

et al. 2022

PLoS ONE

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Background Although many biomarkers have high diagnostic and predictive power for diabetic kidney disease (DKD), less studies were performed for the predictive assessment in DKD and its progression with combined blood and urinary biomarkers. This study aims to explore the predictive significance of joint plasma fibrinogen (FIB) concentration and urinary alpha-1 microglobulin-creatinine (α1-MG/CR) ratio in DKD. Methods A total of 234 patients with type 2 diabetes were enrolled, and their clinical and laboratory data were retrospectively assessed. A ROC curve analysis was performed to evaluate the power of plasma FIB and urinary α1-MG/CR ratio for identifying DKD and advanced DKD, respectively. The predictive power for DKD and advanced DKD was analyzed by regression analysis. Results Plasma FIB and urinary α1-MG/CR levels were higher in patients with DKD than with pure T2D (p<0.001). The multivariate-adjusted odds ratios (ORs) were 5.047 (95%CI: 2.276–10.720) and 2.192 (95%CI: 1.539–3.122) (p<0.001) for FIB and α1-MG/CR as continuous variables for DKD prediction, respectively. The optimal cut-off values were 3.21 g/L and 2.11mg/mmol for identifying DKD, and 5.58 g/L and 11.07 mg/mmol for advanced DKD from ROC curves. At these cut-off values, the sensitivity and specificity of joint FIB and α1-MG/CR were 0.95 and 0.92 for identifying DKD, and 0.62 and 0.67 for identifying advanced DKD, respectively. The area under curve was 0.972 (95%CI: 0.948–0.995) (p<0.001) and 0.611, 95%CI: 0.488–0.734) (p>0.05). The multivariate-adjusted ORs for joint FIB and α1-MG/CR at the cut-off values were 214.500 (95%CI: 58.054–792.536) and 3.252 (95%CI: 1.040–10.175) (p<0.05), respectively. Conclusion The present study suggests that joint plasma FIB concentration and urinary α1-MG/CR ratio can be used as a powerful predictor for general DKD, but it is less predictive for advanced DKD.

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Association of interleukin-36α and interleukin-38 with type 2 diabetes mellitus and diabetic neuropathy

Nassurat,

Salman,

Ad’hiah

2024

Egypt J Intern Med

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Background Interleukin (IL)-36α and IL-38, two novel cytokines of the IL-1 family, have recently been proposed to have a pathophysiological significance in type 2 diabetes mellitus (T2DM). However, there is a paucity of information regarding their association with diabetic neuropathy (DNP). Therefore, this study aimed to explore these interleukins in T2DM without and with DNP, referred to as T2D and DNP, respectively. The predicted interaction of IL-36α and IL-38 with other proteins was also analyzed bioinformatically. In this study, 85 T2D patients, 21 DNP patients, and 109 controls were recruited. Serum IL-36α and IL-38 concentrations were measured with ELISA kits. Results Median (interquartile range) of IL-36α concentrations was significantly greater in T2D and DNP patients compared with controls (62 [54-84] and 52 [45-56] vs. 44 [36-47] pg/mL, respectively; p < 0.001). T2D patients also exhibited significantly greater concentrations of IL-36α than DNP patients (p = 0.004). IL-38 concentrations were significantly greater in T2D and DNP patients compared with controls (208 [149-249] and 200 [130-253] vs. 64 [47-92] pg/mL, respectively; p < 0.001), while T2D and DNP patients showed no significant differences in IL-38 concentrations (p = 0.509). Both cytokines were reliable biomarkers in differentiating diabetic patients from controls, but differentiation performance was better in T2D (area under the curve [AUC] = 0.921 and 0.951, respectively) than in DNP (AUC = 0.881 and 0.844, respectively). Up-regulated IL-36α and IL-38 concentrations were significantly associated with a higher risk of T2D (37.92- and 29.97-fold, respectively) and DNP (10.11- and 32.47-fold, respectively). IL-36α was positively correlated with IL-38 in T2D (correlation coefficient [rs] = 0.487; p < 0.001), but a stronger correlation was found in DNP (rs = 0.683; p < 0.001). IL-36α and IL-38 showed predicted interactions with several cytokines and cytokine receptors of the IL-1 family. Conclusions IL-36α and IL-38 concentrations were upregulated in the serum of T2D and DNP patients. Both cytokines were indicated to be potential discriminating biomarkers associated with higher risk of T2D and DNP. Targeting the axis of their interaction with other cytokines of the IL-1 family may be important for understanding the pathophysiology of T2D and DNP.

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Elevated urinary IL-36α and IL-18 levels are associated with diabetic nephropathy in patients with type 2 diabetes mellitus

Cited by 4 publications

References 33 publications

Urinary N‐acetyl‐β‐d‐glucosaminidase‐creatine ratio is a valuable predictor for advanced diabetic kidney disease

Urinary N‐acetyl‐β‐d‐glucosaminidase‐creatine ratio is a valuable predictor for advanced diabetic kidney disease

Predictive significance of joint plasma fibrinogen and urinary alpha-1 microglobulin-creatinine ratio in patients with diabetic kidney disease

Association of interleukin-36α and interleukin-38 with type 2 diabetes mellitus and diabetic neuropathy

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