Objective: Diabetic nephropathy constitutes a devastating complication in
patients with type 1 diabetes mellitus (T1D) and its diagnosis is traditionally
based on microalbuminuria. The aim of this prospective cross-sectional
follow-up study was to explore the role of serum and urine
neutrophil-gelatinase-associated lipocalin (NGAL) cystatin C (Cys C), YKL-40,
Uric acid (UA) and GDF-15 in unravelling early diabetic nephropathy even in
patients with normoalbuminuria.
Design: Fifty-six euthyroid patients with T1D, with mean age 13.1 (SD: 3.2)
years, and 49 healthy controls with mean age 12.8 (SD: 6.6) were recruited.
Besides standard blood chemistry and urinary albumin excretion, serum and
Urinary NGAL (ELISA) cystatin C (nephelometry), YKL-40(ELISA) and GDF-15(ELISA)
were measured at enrollment and after 12-15 months. GFR was calculated with the
bedside Schwartz formula (S-GFR), Cystatin C Schwartz formula (CysC-eGFR) and
the Lund strategy formula (L-eGFR).
Results: At baseline, mean sNGAL levels, uNGAL, sYKL-40, sGDF-15 and UA were
not significantly different between children with diabetes and controls. At
re-evaluation, mean NGAL value and mean eGFR value in patients with diabetes
were increased (p=0.032 and p=0.003 respectively). sNGAL was positively
correlated with cystatin C (r=0.41, p<0.001), systolic blood pressure z -score
(r=0.3, p=0.031) and creatinine (r=0.32, p=0.010). sNGAL and uric acid
correlated negatively with S-eGFR (r=-0.26, p=0.049 and r=-0.26, p=0.049
respectively) and CysC-eGFR (r=-0.31, p=0.019 and r=-0.27, p=0.041
respectively). sNGAL was negatively correlated with L-eGFR (r=-0.33, p=0.002)
and GDF-15 had a negative correlation with CysC-eGFR (r=-0.27, p=0.039).
Cystatin C had a negative correlation with S-eGFR (r=-0.29, p=0.025), and a
positive correlation with creatinine (r=0.35, p=0.009). No statistically
significant correlation between NGAL, cystatin C, YKL - 40, GDF- 15 and
microalbuminuria was found.
Conclusions: NGAL, GDF-15, uric acid and cystatin C, known markers of renal
injury, correlate with renal function decline in T1D, suggesting that they may
used as supplementary tests to urine albumin excretion in order to unmask early
Diabetic nephropathy, NGAL, Type 1 Diabetes Mellitus, Microvascular complications, Cystatin C