NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up.
OBJECTIVE
Diabetic nephropathy constitutes a major long-term complication in patients with type 1 diabetes mellitus (T1D) and its diagnosis is based on microalbuminuria. The aim of this observational follow-up study was to explore the role of neutrophil-gelatinase-associated lipocalin (NGAL) and cystatin C in unravelling early diabetic nephropathy even in patients with normoalbuminuria.


METHODS
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 NGAL (ELISA) and cystatin C (nephelometry) were measured at enrollment and after 12-15 months. GFR was calculated with the bedside Schwartz formula (eGFR) and the Lund strategy formula (L-eGFR).


RESULTS
At baseline, mean NGAL levels 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). At both baseline and reevaluation, NGAL was positively correlated with cystatin C (r=0.41, p<0.001), systolic arterial pressure z-score (r=0.3, p=0.031) and creatinine (r=0.32, p=0.010). NGAL correlated negatively with eGFR (r=-0.26, p=0.049) and L-eGFR (r=-0.33, p=0.010). Cystatin C had a negative correlation to eGFR (r=-0.29, p=0.025) and a positive one with creatinine (r=0.35, p=0.009) at reevaluation. No statistically significant correlation was found between cystatin C and microalbuminuria (p=0.736).


CONCLUSIONS
NGAL and cystatin C, known markers of renal injury, correlate with renal function decline in T1D, suggesting that they may be used as supplementary tests to urine albumin excretion in order to unmask early renal dysfunction.
Diabetes Centre of the Division of Endocrinology, Diabetes and Metabolism of the First Department of Pediatrics University of Athens, Aghia Sophia Children's Hospital, Athens, Greece, Section of Endocrinology, Department of Medical and Health Sciences, Linkping University, Linkping, Sweden.
Nektraria
N
Papadopoulou-Marketou
Department of Clinical Biochemistry, Aghia Sophia Children's Hospital, Athens, Greece.
Chrysanthi
C
Skevaki
Diabetes Centre of the Division of Endocrinology, Diabetes and Metabolism of the First Department of Pediatrics University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.
Ioanna
I
Kosteria
Division of Endocrinology, "Attikon" Hospital; Athens, Greece.
Melpomeni
M
Peppa
Diabetes Centre of the Division of Endocrinology, Diabetes and Metabolism of the First Department of Pediatrics University of Athens, Aghia Sophia Children's Hospital, Athens, Greece, King Abdulaziz University, Jeddah, S. Arabia.
George P
GP
Chrousos
Department of Clinical Biochemistry, Aghia Sophia Children's Hospital, Athens, Greece.
Ioannis
I
Papassotiriou
Diabetes Centre of the Division of Endocrinology, Diabetes and Metabolism of the First Department of Pediatrics University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.
Christina
C
Kanaka-Gantenbein
D000209:Acute-Phase Proteins; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D055316:Cystatin C / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000097:blood*
D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins