Abstract
Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.
Highlights
IntroductionDiabetes mellitus (DM) is one of the most common and complex metabolic disorders
The urinary levels of component 4b (C4b), complementary factor D (CFD), CXCR6, leukemia inhibitory factor (LIF), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) were markedly increased in diabetic nephropathy patients compared to normal subjects (Figure 6). These results suggested that C4b, CFD, CXCR6, and LIF may be considered as a noninvasive biomarker for early detection of diabetic nephropathy in a clinical trial
These findings revealed the pathways involved in dysregulated genes and the biological implications involved in the progression of diabetic nephropathy in diabetic rat models
Summary
Diabetes mellitus (DM) is one of the most common and complex metabolic disorders. The disease represents one of the greatest medical and socioeconomic challenges throughout the world due to the high rates of diabetic complications and mortality associated with the disease [1]. Diabetic nephropathy (DN) is one of the most devastating microvascular complications of DM, developing in nearly one-third of patients with type 1 or type 2 diabetes [3]. It is by far the most common cause of chronic kidney disease worldwide, frequently leading to end-stage renal disease (ESRD) and the need for renal replacement therapy [4].
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