Abstract
Diabetic nephropathy (DN) is a serious microvascular complication in childhood diabetes and microalbuminuria has been a solid indicator in the assessment of DN. Nevertheless, renal injury may still occur in the presence of normoalbuminuria (NA) and various tubular injury biomarkers have been proposed to assess such damage. This case-controlled study aimed to evaluate plasma and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 (KIM-1) levels in diabetic children particularly in those with normo- and high-NA stages and determine their role in predicting DN. Fifty-four children/adolescents with type 1 and 2 diabetes and forty-four controls aged 7–18 years were included. The baseline clinical and laboratory characteristics including plasma and urinary biomarkers were compared. The plasma KIM-1 levels were significantly higher in diabetic children than in the controls and in high-NA children than normo-NA children. Glycosylated hemoglobin (HbA1c) was identified as a significant risk factor for increased plasma KIM-1. The optimal cutoff for HbA1c when the plasma KIM-1 was > 23.10 pg/mL was 6.75% with an area under the curve of 0.77. For diabetic children with mildly increased albuminuria, the plasma KIM-1 complementary to MA may help increase the yield of detecting DN. Our findings also suggested an HbA1c cutoff of 6.75% correlated with increased plasma KIM-1.
Highlights
Diabetic nephropathy (DN) is considered to be one of the most serious microvascular complications in terms of the mortality and morbidity of diabetic patients
All children with type 1 diabetes mellitus (T1DM) were treated with a subcutaneous insulin injection while 19 (82.6%) children with type 2 diabetes mellitus (T2DM) were treated with metformin
Age (p < 0.001), serum C-reactive protein (CRP) (p < 0.001), glucose (p < 0.001), Cr (p < 0.001), HbA1c (p < 0.001) and the UACR (p < 0.001) were significantly higher whereas serum c-peptide (p < 0.001), HOMA-β (p < 0.001) and uric acid (P = 0.011) levels were significantly lower in diabetic children than in the controls
Summary
Diabetic nephropathy (DN) is considered to be one of the most serious microvascular complications in terms of the mortality and morbidity of diabetic patients. Albuminuria is a well-recognized and early marker of DN and of the progression of vascular complications such as cardiovascular diseases [3,4]. Numerous studies have demonstrated that MA could not be a specific indicator of renal injury and its utility in predicting DN progression is limited because various pathological changes and an eGFR decline are observed in the presence of NA [2,6]. Progressive renal decline could be initiated at even 10% NA, 30% MA and 50% proteinuric states in DM patients [7] Other vascular complications such as diabetic retinopathy and cardiovascular diseases may occur in diabetic patients in a normal to mildly increased albuminuric state; recent studies have suggested a revised threshold for MA [8,9]
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