Panel of novel urine biomarkers for incident microalbuminuria in people with type 2 diabetes mellitus

Abstract

Aim The need to identify novel biomarkers for early diagnosis and treatment of diabetic nephropathy is widely recognized. However, only a few studies have investigated the association between biomarkers and the onset of albuminuria. In this study, we aimed to investigate a panel of biomarkers suitable for predicting microalbuminuria. Methods Some 346 Japanese people with type 2 diabetes exhibiting normoalbuminuria were studied. The endpoint was defined as the onset of microalbuminuria. Thirty biomarkers were selected from among urinary biomarkers described in previous studies. A panel of biomarkers was selected using least absolute shrinkage and selection operator (LASSO). The prognostic performance of the developed panel was evaluated. Results During a mean follow-up of 6.2 years, 45 people progressed to microalbuminuria. A composite panel of six biomarkers (monocyte chemoattractant protein-1, osteopontin, soluble human tumour necrosis factor receptor-1, tenascin C, vascular endothelial growth factor-A and kidney injury molecule-1) was developed using LASSO. Compared with the basal model comprising estimated GFR and urinary albumin-to-creatinine ratio, addition of these six biomarkers significantly increased the overall C index from 0.773 to 0.824 (P = 0.019). Net reclassification improvement and integrated discrimination improvement were estimated to be 0.412 (P = 0.049) and 0.040 (P = 0.040), respectively. Decision curve analysis also showed that the model with the six novel biomarkers had a better prognostic value for predicting the onset of microalbuminuria. The optimism was moderate or negligible according to measures. Conclusions The panel consisting of six novel urinary biomarkers effectively predicted incident microalbuminuria in people with type 2 diabetes.

Novel Cardiovascular Risk Factors in Patients with Diabetic Kidney Disease

“…Moreover, KIM-1 levels correlate with GFR and urinary albumin excretion [ 5 , 8 , 24 , 25 , 26 ]. Elevated KIM-1 levels also predict the onset of microalbuminuria [ 27 ], a decline in GFR and the incidence of ESRD in patients with either T2DM or type 1 DM (T1DM) [ 13 , 28 , 29 , 30 ].…”

Integrated Analysis of Single-Cell RNA-seq and Bulk RNA-seq in the Identification of a Novel ceRNA Network and Key Biomarkers in Diabetic Kidney Disease

“…55 Clinical research reported that tenascin-C (TNC) can be used as a prognostic indicator to predict the development of microalbuminuria in patients with DKD. 56 Mechanistic studies further suggested that TNC can promote the development and progression of DKD by interfering with the TNC/TLR4/NF-κB p65/miR-155-5p pathway. 57 Furthermore, we investigated the expression profiles of these biomarkers using scRNA-seq and found that most of the hub genes (VCAN, C3, CP and TIMP1) were highly expressed in fibroblast cells; this was consistent with a previous bulk RNA-seq study, which reported that fibroblasts were expressed at significantly higher levels in patients with advanced DKD and negatively associated with GFR.…”

Urinary liver‐type fatty acid‐binding protein is a predictor of mortality in individuals with type 2 diabetes

“…Diabetic nephropathy remains a common complication of diabetes. Genetic aetiology of diabetes-related kidney disease has recently been investigated, 1 and several urinary biomarkers for the prediction of the development of diabetic nephropathy have been identified 2 ; however, prognostic markers which can be used in clinical practice are limited. Liver-type fatty acid-binding protein (L-FABP), which is expressed in hepatocytes and the proximal tubules of the kidney, has been reported to be involved in fatty acid metabolism and has attracted attention as a biological marker for identifying and predicting a decline in renal function.…”