دور المؤشرات المناعية، الإنترلوكين-40 والإنترلوكين-41 في مصل مرضى السكّري المصابين بالمرحلة النهائية من مرض الكلى

Role of Immunological Biomarkers, interleukin-40 and Interleukin-41 in Serum of Diabetic Patients with End Stage Renal Disease

Abstract

Diabetic kidney disease (DKD) represents a one of severe chronic complications of diabetes mellitus and constitutes one of the primary causes of end-stage kidney disease globally. DKD also lead to changes in the hemodynamic of the immune cells components and pathophysiological inflammation which influence in the production, suppression, or downregulation of mediators.
this study aimed to evaluate IL-40 and IL-41 levels in diabetic patients generally and those with diabetic kidney disease specifically compared to healthy controls, determine the predictive value of these biomarkers, and investigate relationships between these novel indicators and traditional laboratory markers (HbA1c, creatinine, urea, ferritin). The study adopted a case-control design with 128 participants: 42 DKD patients, 43 diabetic patients without kidney disease (DM), and 43 healthy individuals. DKD and DM patients were recruited from Imam AL-Hussein Hospital in Karbala, while controls were collected from Al-Majar Al-Kabir Hospital in Maysan, during period between Non.2024 to Jan.2025. Blood samples were analyzed using ELISA technique )HUMAN German company kits( to measure IL-40 and IL-41 levels, alongside other laboratory indicators. Statistical analysis employed ANOVA, Kruskal-Wallis tests, correlation analysis, and ROC curves.
Key results revealed that IL-40 levels decreased by approximately 47.2% (15.8 ± 4.0 pg/mL) in DKD patients and 52.8% (14.1 ± 3.7 pg/mL) in DM patients, compared to healthy controls (29.9 ± 8.7 pg/mL). Similarly, IL-41 levels declined by about 82.4% (0.53 ± 0.18 pg/mL) in DKD patients and 78.7% (0.64 ± 0.11 pg/mL) in DM patients, relative to healthy individuals (3.01 ± 0.98 pg/mL), with all differences being statistically significant (p < 0.001). IL-41 demonstrated excellent predictive performance with an AUC of 98.4% and 95.3% accuracy in distinguishing DKD patients from controls, whereas IL-40 showed good predictive utility with an AUC of 89.6% and 90.6% accuracy. additional biochemical changes in DKD patients included elevated urea and creatinine, decreased hemoglobin, and disturbed calcium and phosphate levels. No significant correlations were found between IL-40/IL-41 levels and traditional clinical indicators, except for a positive correlation between IL-40 and IL-41 in the DKD group (r=0.335, p=0.030).
This study confirmed a significant decrease in the levels of IL-40 and IL-41 in previously diagnosed diabetic kidney disease and diabetic patients compared to healthy individuals, suggested a potential role for these markers as complementary or predictive biological indicators. Notably, IL-41 demonstrated very high sensitivity and specificity in distinguishing known diabetic kidney disease patients.
However, study limitations included small sample size, lack of assessment of other inflammatory factors, and absence of long-term follow-up. The study recommends larger longitudinal clinical research to verify integrating these indicators into early diagnosis programs. In conclusion, this study provided initial evidence supporting the predictive potential and role of IL-40 and especially IL-41 in diabetic kidney disease of previously diagnosed patients, and due to the lack of correlation with traditional markers, it is recommended to conduct large-scale and longitudinal studies to validate these findings and explore their clinical applicability especially in the early stages of the disease to confirm their capability for early diagnosis or prediction.