NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up

Abstract

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. 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 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.

Nephro-toxic effects of intraperitoneally injected EGCG in diabetic mice: involvement of oxidative stress, inflammation and apoptosis

“…Moreover, kidney injury was confirmed by significant increase in both serum cystatin C and NGAL levels. The significant correlation between NGAL, cystatin C and glomerular filtration rate decline supported the prognostic role of both markers in revealing early structural renal damage before an overt renal impairment becomes evident22. Diabetic mice receiving EGCG showed no significant alteration in BUN level compared to diabetic and normal mice which indicates that the animals were not in a lethal condition as the elevation in BUN is known to have a negative impact on survival23.…”

NGAL as an Early Predictive Marker of Diabetic Nephropathy in Children and Young Adults with Type 1 Diabetes Mellitus

“…In previous studies, NGAL was reported as effective in the early diagnosis of acute kidney injury (AKI) in several clinical settings [23–25] and was also validated as a significant prognostic factor in cardiovascular morbidity [26]. The association between the early tubular lesions in nonalbuminuric patients with T1D and NGAL was further supported by recently published studies [18, 19, 21]. …”

“…Several studies have reported that nonalbuminuric subjects, including prepubertal children with long-standing diabetes, often have glomerular basement membrane (GBM) thickening, mesangial expansion [15, 16], and significant glomerulopathy lesions [17, 18]. Glomerular and renal tubular interstitial injury plays a role in the pathogenesis of DN [19], and various tubular markers have been assessed in the early detection of DN [10, 20].…”

Evaluation of Haptoglobin and Neutrophil Gelatinase Associated Lipocalin in Iraqi Patient with Type 2 Diabetic Nephropathy

“…Venous blood specimens were collected from diabetic patients and controls into two sorts of vacutainer tubes as follows: first venous blood sample was collected in plain tube and left to clot for (30min) at room temperature and then centrifuge to separate at (3000rpm) for (10min) utilized for the biochemical examines. Second tube with EDTA, mixed gently by the shaker and then centrifuged to separate the plasma for 15min at 1000xg (2)(3)(4)(5)(6)(7)(8) …”

“…Tubular excretion of NGAL associates with the acuteness of chronic kidney failure, as in autosomal dominant polycystic renal disease or glomerulonephritis. [7,8] Haptoglobin is a hemoglobin-binding protein existing in the plasma. Its function is principal to control the destiny of hemoglobin out from red platelets after either extravascular or intravascular hemolysis.…”