👤 Sriraman Devarajan

Angiopoietins are crucial growth factors for maintaining a healthy, functional endothelium. Patients with type 2 diabetes (T2D) exhibit significant levels of angiogenic markers, particularly Angiopoietin-2, which compromises endothelial integrity and is connected to symptoms of endothelial injury and failure. This report examines the levels of circulating angiopoietins in people with T2D and diabetic nephropathy (DN) and explores its link with ANGPTL proteins. We quantified circulating ANGPTL3, ANGPTL4, ANGPTL8, Ang1, and Ang2 in the fasting plasma of 117 Kuwaiti participants, of which 50 had T2D and 67 participants had DN. The Ang2 levels increased with DN (4.34 ± 0.32 ng/mL) compared with T2D (3.42 ± 0.29 ng/mL). This increase correlated with clinical parameters including the albumin-to-creatinine ratio (ACR) (r = 0.244, Show less

ANGPTL4 is a glycoprotein that is involved in regulating triglyceride metabolism by inhibiting LPL activity under fasting conditions. Additionally, ANGPTL4 has been suggested as a link between hypertriglyceridemia and albuminuria in the nephrotic syndrome. In this study, we examined levels of circulating ANGPTL4 in people with diabetic nephropathy (DN) and its association with established DN-associated proteins such as IGFBP1 and IGFBP4. We quantified circulating ANGPTL4, IGFBP1, IGFBP3, and IGFBP4 in fasting plasma samples of 122 Kuwaiti participants using a multiplexing assay. The study involved 36 controls, as well as 86 people with type 2 diabetes (T2D) including 37 people with normal kidney function and 49 people with DN. ANGPTL4 level was increased in people with DN (241.56 ± 14.1 In this study, our data showed a significant increase in circulating ANGPTL4, IGFBP1, and IGFBP4 in patients with DN. The elevation in ANGPTL4 correlated significantly with clinical markers of DN such as ACR, serum creatinine, and eGFR, as well as IGFBP1 and IGFBP4. Altogether, this suggests a potential role for ANGPTL4 in DN perhaps through its role in inhibiting LPL activity and promotes ANGPTL4 as a biochemical marker for the detection of a diabetic kidney disease in patients with T2D. Show less

There is a paucity of sensitive and specific biomarkers for the early prediction of CKD progression. The recent application of innovative technologies such as functional genomics, proteomics, and biofluid profiling has uncovered several new candidates that are emerging as predictive biomarkers of CKD. The most promising among these include urinary proteins such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and liver-type fatty acid binding protein. In addition, an improved understanding of the complex pathophysiologic processes underlying CKD progression has also provided discriminatory biomarkers of CKD progression that are being actively evaluated. Candidates included in this category are plasma proteins such as asymmetric dimethylarginine, adiponectin, apolipoprotein A-IV, fibroblast growth factor 23, neutrophil gelatinase-associated lipocalin, and the natriuretic peptides, as well as urinary N-acetyl-β-d-glucosaminidase. This review represents a critical appraisal of the current status of these emerging CKD biomarkers. Currently, none of these are ready for routine clinical use. Additional large, multicenter prospective studies are needed to validate the biomarkers, identify thresholds and cut-offs for prediction of CKD progression and adverse events, assess the effects of confounding variables, and establish the ideal assays. Show less