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

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.

FIGURE 1

Conceptual framework; variables in solid rectangles represent directly measured variables, in oval represent a latent, indirectly measured variable, and in a dotted rectangle represent unmeasured truly targeted distal outcome; Cys C, cystatin C; RI, renal resistance index; KIM-1, kidney injury molecule-1; eGFR, estimated glomerular filtration rate; Albumin, urinary albumin; Creatinine, serum creatinine; DM-T1, diabetes mellitus type 1; HbA1c, glycated hemoglobin A1c; BP, higher blood pressure; BMI, body mass index centile.

FIGURE 2

The MIMIC model with standardized estimates predicted using the maximum likelihood; latent factor variance fixed to 1; and numbers in parentheses are 95% confidence intervals. Cys C, cystatin C; RI, renal resistance index; KIM-1, kidney injury molecule-1; eGFR, estimated glomerular filtration rate; Albumin, urinary albumin; Creatinine, serum creatinine; Duration, duration of diabetes mellitus type 1; HbA1c, glycated hemoglobin A1c; BP, higher blood pressure; BMI, body mass index percentile (n = 75).