Cystatin C, renal resistance index, and kidney injury molecule-1 are potential early predictors of diabetic kidney disease in children with type 1 diabetes

Ivana Trutin; Zarko Bajic; Daniel Turudic; Andrea Cvitkovic-Roic; Danko Milosevic

doi:10.3389/fped.2022.962048

Cystatin C, renal resistance index, and kidney injury molecule-1 are potential early predictors of diabetic kidney disease in children with type 1 diabetes

Front Pediatr. 2022 Jul 29:10:962048. doi: 10.3389/fped.2022.962048. eCollection 2022.

Authors

Ivana Trutin¹, Zarko Bajic², Daniel Turudic³, Andrea Cvitkovic-Roic^{4

5}, Danko Milosevic^{6

7}

Affiliations

¹ Department of Pediatrics, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia.
² Research Unit "Dr. Mirko Grmek", University Psychiatric Hospital "Sveti Ivan", Zagreb, Croatia.
³ Department of Pediatrics, University Hospital Centre Zagreb, Zagreb, Croatia.
⁴ Helena Clinic for Pediatric Medicine, Zagreb, Croatia.
⁵ Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
⁶ School of Medicine, University of Zagreb, Zagreb, Croatia.
⁷ Department of Pediatrics, General Hospital Zabok and Hospital of Croatian Veterans, Bracak, Croatia.

Abstract

Background: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease in patients with diabetes mellitus type I (DM-T1). Microalbuminuria and estimated glomerular filtration rate (eGFR) are standard predictors of DKD. However, these predictors have serious weaknesses. Our study aimed to analyze cystatin C, renal resistance index, and urinary kidney injury molecule-1 (KIM-1) as predictors of DKD.

Methods: We conducted a cross-sectional study in 2019 on a consecutive sample of children and adolescents (10-18 years) diagnosed with DM-T1. The outcome was a risk for DKD estimated using standard predictors: age, urinary albumin, eGFR, serum creatinine, DM-T1 duration, HbA1c, blood pressure, and body mass index (BMI). We conducted the analysis using structural equation modeling.

Results: We enrolled 75 children, 36 girls and 39 boys with the median interquartile range (IQR) age of 14 (11-16) years and a median (IQR) duration of DM-T1 of 6 (4-9) years. The three focal predictors (cystatin C, resistance index, and urinary KIM-1) were significantly associated with the estimated risk for DKD. Raw path coefficients for cystatin C were 3.16 [95% CI 0.78; 5.53; p = 0.009, false discovery rate (FDR) < 5%], for renal resistance index were -8.14 (95% CI -15.36; -0.92; p = 0.027; FDR < 5%), and for urinary KIM-1 were 0.47 (95% CI 0.02; 0.93; p = 0.040; FDR < 5%).

Conclusion: Cystatin C, renal resistance index, and KIM-1 may be associated with the risk for DKD in children and adolescents diagnosed with DM-T1. We encourage further prospective cohort studies to test our results.

Keywords: adolescent; biomarkers; children; cystatin C; diabetes mellitus type 1; diabetic nephropathy; renal resistance index; urinary kidney injury molecule kIM-1.