Table 1.
Biomarkers of diabetic nephropathy in children and adolescents with T1DM.
| Study Design | Study Population | Biomarkers Classification | Biomarkers and Outcomes | Ref. |
|---|---|---|---|---|
| Case–control study | Total sample = 99 T1DM cases = 59 (MAU = 11; NAU = 48) Healthy controls = 40 Age = 9–19 years |
Tubular injury | Higher urinary loss of RBP and β-NAG in diabetic children with MAU (406 µg/dL and 11.16 Ug/Cr) than those with NAU (386.13 µg/dL and 6.88 Ug/Cr) and healthy controls (151.8 µg/dL and 3.8 Ug/Cr). Children with high baseline urinary RBP/β-NAG were assessed every 6 months |
[33] |
| Case–control study | Total sample = 90 T1DM cases = 60 (MAU = 30; NAU = 30) Healthy controls = 30 Age = ~10 years |
Tubular injury | Children with MAU had higher urinary β-NAG levels than NAU and healthy children | [34] |
| Case–control study | Total sample = 37 T1DM cases with DNE = 22Healthy controls = 15 Age = ~13 years |
Tubular injury | Higher serum NGAL (sNGAL) and urinary NGAL (uNGAL) levels were detected in children with T1DM compared to healthy controls (sNGAL = 867 ng/mL vs. 655 ng/mL; uNGAL = 420 ng/mL vs. 156 ng/mL) | [35] |
| Case–control study | Total sample = 111 T1DM cases (MAU and NAU) = 76 Healthy controls = 35 Age = ~12 years |
Tubular injury | Higher uNGAL and uNGAL/Cr levels were reported in children with MAU (145 ng/mL and 104 ng/mg) and NAU (92 ng/mL and 121 ng/mg) compared to healthy controls (21 ng/mL and 32 ng/mg) | [36] |
| Case–control study | Total sample = 90 T1DM cases = 60 (MAU = 31; NAU = 29) Healthy controls = 30 Age = ~13 years |
Tubular injury | Higher serum CysC (0.84 mg/dL) and urinary CypA (26.9 ng/mL) and CypA/Cr ratio (0.38 ug/gm) were reported in children with MAU than those with NAU (CysC = 0.69 mg/dL; CypA = 17.85 ng/mL; CypA/Cr ratio = 0.22 ug/gm) and healthy controls (CysC = 0.53 mg/dL; CypA = 15.65 ng/mL; CypA/Cr ratio = 0.19 ug/gm) | [37] |
| Case–control study | Total sample = 61 T1DM cases = 29 (MAU = 3; NAU = 20) Healthy controls = 32 Age = ~16 years |
Tubular injury | Urinary L-FABP/Cr levels were higher in children with MAU (9.8 ng/mg) than those with NAU (6.3 ng/mg) and healthy controls (2.9 ng/mg) | [38] |
| Cross-sectional study | Total sample = 68 T1DM children = 50 (MAU = 12; NAU = 38) Healthy children = 18 Age = ~14 years |
Tubular injury | Children with MAU demonstrated increased uNGAL (39.1 ng/mL) compared to those with NAU (15.6 ng/mL) and healthy controls (5.6 ng/mL) | [39] |
| Cross-sectional study | Total sample = 49 T1DM children = 34 Healthy children = 15 Age = ~14 years |
Tubular injury | Higher uNGAL levels both in S and E fractions were detected in T1DM children than in healthy counterparts | [40] |
| Cross-sectional study | Total sample = 75 children with T1DM Age = 10–18 years |
Tubular injury | Increased serum/urinary sCysC, KIM-1, and RI levels in T1DM children | [41] |
| Cross-sectional study | Total sample = 779 children with T1DM Age = ~16 years |
Tubular injury | Increased serum sCysC and Cr, and decreased eGFR levels in T1DM children | [42] |
| Cross-sectional study | Total sample = 31 T1DM children = 21 Healthy children = 10 Age = ~16 years |
Tubular injury and OS | Higher uNGAL/Cr and pentosidine/Cr were associated with urine microalbumin/Cr | [43] |
| Prospective cohort study | Total sample = 105 T1DM children = 56 Healthy children = 49 12–15-month follow-up period Age = ~13 years |
Tubular injury | Increased serum NGAL and sCysC in T1DM children compared to healthy counterparts over time | [44] |
| Cross-sectional study | Total sample = 100 T1DM children with DNE = 50 Healthy children = 50 Age = ~10 years |
Inflammation | Higher uTGF-β1 levels were reported in T1DM children than in healthy counterparts | [45] |
| Cross-sectional study | Total sample = 98 T1DM children = 49 Normoglycemic children = 49 Age = ≤19 years |
Inflammation | Higher mRNA levels of inflammatory genes were observed in T1DM compared to healthy controls. These genes may lead to DNE progression in children with T1DM | [46] |
| Retrospective cohort study | Total sample = 100 T1DM with DNE = 34 T1DM without DNE = 66 Age = ~12 years |
Inflammation | Increased inflammatory markers, including PLR, NLR, SIRI, and SII acting as early predictors of DNE in T1DM children | [47] |
| Case–control study | Total sample = 198 T1DM cases = 158 Healthy controls = 40 Age = ~13 years |
Endothelial dysfunction | Children with T1DM had lower uEGF levels than healthy controls (46.5 vs. 86.3 ng/mL). Thus, uEGF is considered a potential biomarker of DNE in children with T1DM. | [48] |
| Cross-sectional study | Total sample = 72 children with T1DM Age = ≤19 years |
Endothelial dysfunction | Higher plasma levels LRG1 were detected in T1DM children and associated with sCysC-based eGFR decline. LRG1 is therefore considered as an early biomarker of DNE progression | [49] |
| Cross-sectional study | Total sample = 90 T1DM children = 60 (MAU = 30; non-albuminuric = 30) Healthy children = 30 Age = ~13 years |
Endothelial dysfunction | Higher serum Angpt-2 levels were reported in MAU group than other groups (MAU = 148 ng/L; non-albuminuric = 125.3 ng/L; healthy controls = 90.5 ng/L). Therefore, Angpt-2 acts as a useful diagnostic biomarker for DNE in children with T1DM | [50] |
| Cross-sectional study | Total sample = 100 T1DM cases = (MAU = 24 with DNE; NAU without DNE = 26) Healthy controls = 50 Age = ~14 years |
MicroRNAs | Children with MAU demonstrated higher umiR-377 and lower umiR-216a expression compared to other groups | [51] |
| Cross-sectional study | Total sample = 70 T1DM children (with DNE = 45; without DNE = 25) Age = ≤18 years |
MicroRNAs | Children with DNE compared to those without demonstrated higher expression of miRNA-377 and miRNA-93, and lower expression of miRNA-25 | [52] |
| Cross-sectional study | Total sample = 79 children with T1DM Age = ~16 years |
MicroRNAs and others | KL has been considered as a potential biomarker of early DNE in children with T1DM. T1DM children demonstrated increased serum levels of miR-192 and decreased serum levels of KL | [53] |
| Case–control study | Total sample = 180 T1DM cases = (MAU = 60; NAU = 60) Healthy controls = 60 Age = ~16 years |
Others | Higher MK levels have been detected in children with MAU and NAU than in healthy controls (MAU = 1847.2 pg/mL; NAU = 1158.4 pg/mL; 658.3 pg/mL). This suggests that MK is a useful biomarker for the detection of DNE in children with T1DM | [54] |