Normal-range albuminuria does not exclude nephropathy in diabetic children

Abstract

Clinically detectable diabetic nephropathy (DN) begins with the development of microalbuminuria (MA). However, early renal dysfunction may be overlooked despite using that method. On the other hand, the gold standard in DN detection-that is, renal biopsy-is highly invasive. The aim of this study was to evaluate the level of neutrophil-gelatinase-associated lipocalin (NGAL) and interleukin (IL)-18 and their relations to albumin excretion rate (AER) in children with normal-range albuminuria, e.g. in those considered as not presenting diabetic nephropathy. The study group consisted of 22 children (age 12.7 +/- 3.5 years) with type 1 diabetes mellitus (T1DM). Long-term glycemic control was assessed on hemoglobin A1c (HbA1c) levels (8.52 +/- 1.78%). All patients presented normal estimated glomerular filtration rate (eGFR) (141 +/- 23 ml/min/1.73 m(2)) and normal urinary albumin excretion (13.09 +/- 7.63 mg/24 h). Fourteen healthy children served as a control group. Children with T1DM showed increased NGAL values with respect to controls-interestingly, both in serum (sNGAL) (867.43 +/- 341.98 vs. 655.29 +/- 196.17 ng/ml; p = 0.04) and in urine (uNGAL) (420.04 +/- 374.16 vs. 156.53 +/- 185.18 ng/ml, p = 0.04). IL-18 levels were not different in both groups both in serum (58.52 +/- 20.11 vs. 69.79 +/- 58.76 ng/ml; NS) and in urine (14.53 +/- 12.74 vs. 14.60 +/- 10.92 ng/ml; NS). Despite the relatively small study group, the positive correlation between sNGAL and AER was found [AER (mg/24 h) = 3.1893 + 0.01141 x sNGAL (ng/ml); r = 0.51; p = 0.014] as well as between uNGAL and AER [AER (mg/24 h) = 8.7538 + 0.01032 x uNGAL (ng/ml); r = 0.51; p = 0.016]. No relationship between sNGAL and uNGAL, and GFR and HbA1c were found. Normal-range albuminuria does not exclude diabetic nephropathy defined as increased sNGAL and uNGAL concentration. NGAL measurement can be more sensitive than MA and may become a useful tool for evaluating renal involvement in diabetic children.

Urinary Neutrophil Gelatinase Associated Lipocalin as a Marker of Tubular Damage in Type 2 Diabetic Patients with and without Albuminuria

“…Similar to our results Woo et al found inverse correlation between UNGAL with eGFR while he did not find any correlation with albuminuria [37]. In contrast to our results, Zachwieja J. et al found correlation between UNGAL and UAE while he did not find any correlation with eGFR and HbA1c [32]. In our study, linear regression analysis demonstrated that independent predictors of log UNGAL/Cr ratio were HbA1c, urine creatinine and eGFR.…”

“…NGAL measurement could be useful for the evaluation of early renal involvement in the course of diabetes [31]. Also in children some reports showed that serum and UNGAL were elevated in diabetic children without albuminuria and concluded that Normal-range albuminuria does not exclude diabetic nephropathy defined as increased serum and UNGAL concentration and NGAL measurement can be more sensitive than microalbumin and may become a useful tool for evaluating renal involvement in diabetic children [32]. Some other studies showed inconsistency with our results.…”

Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus

“…20 Previous studies showed some renal tubular biomarkers to be increased before microalbuminuria in diabetic children. Zachwieja et al 21 notified that urine neutrophil gelatinase-associated lipocalin (NGAL) levels were higher in normoalbuminuric children with T1DM than in controls. Also Soltysiak et al 22 found higher urine NGAL and lower urine cathepsin-L levels in normoalbuminuric diabetic children than in control group and the authors concluded that the changes in these parameters indicate early signs of diabetic kidney injury, especially tubular injury.…”

“…Also Soltysiak et al 22 found higher urine NGAL and lower urine cathepsin-L levels in normoalbuminuric diabetic children than in control group and the authors concluded that the changes in these parameters indicate early signs of diabetic kidney injury, especially tubular injury. 21,22 Similarly, HSP70 may indicate early diabetic kidney injury because it has been shown in experimental models of acute kidney injury and gentamicin-induced renal tubular injury in Human Kidney tubular cell line (HK-2) that uHSP70 is a useful marker for early detection of proximal tubular cell injury. 23,24 DN is a consequence of exposure to consistent high plasma glucose concentration and various other metabolic factors such as advanced glycosylated end products (AGEs), oxidative stress, growth factors, and cytokines.…”

Importance of diabetic nephropathy in childhood. Clinical findings and basic research in the past decades

“…Igazolták továbbá, hogy ACEi lisinopril adását követően a vizeletben ürülő NGAL mennyisége csökken [30]. Gyermekekben eddig egy, kis esetszámú vizsgálat történt, amelyben kimutatták, hogy azokban az 1-es típusú betegekben, akikben az albuminürítés a normálérték felső határán, illetve MA-s tartományban van, mind a szérum-, mind a vizelet-NGAL mennyisége megnő, a normális vesefunkciós paraméterek (kreatinin, BUN, GFR) ellenére [31]. Mindezek arra utalnak, hogy az új biomarkerek, például az NGAL potenciálisan korábban jelezhetik a vesekároso-dás meglétét, mint a jelenleg használt mérési módszerek.…”