Assessment of urinary NGAL for differential diagnosis and progression of diabetic kidney disease

Duan, Suyan; Chen, Jiajia; Wu, Lin; Nie, Guangyan; Sun, Lianqin; Zhang, Chengning; Huang, Zhimin; Xing, Changying; Zhang, Bo; Yuan, Yanggang

doi:10.1016/j.jdiacomp.2020.107665

Cited by 31 publications

(23 citation statements)

References 35 publications

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“…In several observational single-center follow-up studies, elevated urine NGAL level was shown to be associated with urinary albumin excretion ( 80 ), the rapid decline in eGFR and increased serum creatinine ( 81 ), renal progression to ESKD ( 83 ), and progressive tubular structural and functional impairment ( 84 ). Consistently, our cohort study found that the best predictive cutoff value of urinary NGAL to creatine ratio (uNCR) for DKD diagnosis was 60.685 ng/mg, and T2DM patients with the increased level of uNCR had a higher risk of nephrotic-range proteinuria and worse renal outcome ( 82 ). Furthermore, a more recent report from the CRIC study conducted at seven US clinical centers provided solid evidence that higher urinary NGAL levels were not only strongly associated with cardiac markers, but were also linked to an approximately twofold or greater risk of CKD progression in patients with DM ( 10 ).…”

Section: Challenges and Progress In The Application Of Novel Tubular Biomarkersmentioning

confidence: 62%

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

et al. 2021

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Over decades, substantial progress has been achieved in understanding the pathogenesis of proteinuria in diabetic kidney disease (DKD), biomarkers for DKD screening, diagnosis, and prognosis, as well as novel hypoglycemia agents in clinical trials, thereby rendering more attention focused on the role of renal tubules in DKD. Previous studies have demonstrated that morphological and functional changes in renal tubules are highly involved in the occurrence and development of DKD. Novel tubular biomarkers have shown some clinical importance. However, there are many challenges to transition into personalized diagnosis and guidance for individual therapy in clinical practice. Large-scale clinical trials suggested the clinical relevance of increased proximal reabsorption and hyperfiltration by sodium-glucose cotransporter-2 (SGLT2) to improve renal outcomes in patients with diabetes, further promoting the emergence of renal tubulocentric research. Therefore, this review summarized the recent progress in the pathophysiology associated with involved mechanisms of renal tubules, potential tubular biomarkers with clinical application, and renal tubular factors in DKD management. The mechanism of kidney protection and impressive results from clinical trials of SGLT2 inhibitors were summarized and discussed, offering a comprehensive update on therapeutic strategies targeting renal tubules.

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Section: Challenges and Progress In The Application Of Novel Tubular Biomarkersmentioning

confidence: 62%

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

et al. 2021

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“…236 However, other studies have shown that urine NGAL did not provide additional information beyond the standard renal biomarkers in predicting outcomes in patients with ESRD but did improve prediction of CKD progression in elderly patients with low-grade proteinuria 237 and in diabetic patients. 238 Similarly, plasma/serum NGAL improved upon serum creatinine and eGFR in predicting the severity of tubulointerstitial infiltrates and fibrosis in patients with early CKD and predicted renal dysfunction in patients with early diabetes and children with CKD. [239][240][241] In the clinical veterinary setting, urinary and, to a lesser extent, serum NGAL have shown promise as biomarkers of CKD progression.…”

Section: Neutrophil Gelatinase-associated Lipocalinmentioning

confidence: 93%

A Review of Specific Biomarkers of Chronic Renal Injury and Their Potential Application in Nonclinical Safety Assessment Studies

et al. 2021

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A host of novel renal biomarkers have been developed over the past few decades which have enhanced monitoring of renal disease and drug-induced kidney injury in both preclinical studies and in humans. Since chronic kidney disease (CKD) and acute kidney injury (AKI) share similar underlying mechanisms and the tubulointerstitial compartment has a functional role in the progression of CKD, urinary biomarkers of AKI may provide predictive information in chronic renal disease. Numerous studies have explored whether the recent AKI biomarkers could improve upon the standard clinical biomarkers, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio, for predicting outcomes in CKD patients. This review is an introduction to alternative assays that can be utilized in chronic (>3 months duration) nonclinical safety studies to provide information on renal dysfunction and to demonstrate specific situations where these assays could be utilized in nonclinical drug development. Novel biomarkers such as symmetrical dimethyl arginine, dickkopf homolog 3, and cystatin C predict chronic renal injury in animals, act as surrogates for GFR, and may predict changes in GFR in patients over time, ultimately providing a bridge from preclinical to clinical renal monitoring.

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“…Gelatinase and ceruloplasmin are two types of proteins that have been identified in urine and are closely related to the development of DKD ( 120 , 142 , 143 ). There is ample evidence in laboratory animals and humans that gelatinase is reduced in early and late DKD kidney tissues.…”

Section: Microvesselsmentioning

confidence: 99%

Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications

Chen

Wang

et al. 2021

Front. Endocrinol.

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Diabetic vascular complications (DVC) including macrovascular and microvascular lesions, have a significant impact on public health, and lead to increased patient mortality. Disordered intercellular cascades play a vital role in diabetic systemic vasculopathy. Exosomes participate in the abnormal signal transduction of local vascular cells and mediate the transmission of metabolic disorder signal molecules in distant organs and cells through the blood circulation. They can store different signaling molecules in the membrane structure and release them into the blood, urine, and tears. In recent years, the carrier value and therapeutic effect of exosomes derived from stem cells have garnered attention. Exosomes are not only a promising biomarker but also a potential target and tool for the treatment of DVC. This review explored changes in the production process of exosomes in the diabetic microenvironment and exosomes’ early warning role in DVC from different systems and their pathological processes. On the basis of these findings, we discussed the future direction of exosomes in the treatment of DVC, and the current limitations of exosomes in DVC research.

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Assessment of urinary NGAL for differential diagnosis and progression of diabetic kidney disease

Cited by 31 publications

References 35 publications

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

A Review of Specific Biomarkers of Chronic Renal Injury and Their Potential Application in Nonclinical Safety Assessment Studies

Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications

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