Abstract
Diabetic nephropathy (DN) is a major complication in diabetic patients. Microalbuminuria testing is used to identify renal disease; however, its predictive value is questionable. We aimed to identify urinary biomarkers to early diagnosis nephropathy before identifiable alternations in kidney function or urine albumin excretion occurs. Proteomic approaches were used to identify potential urinary biomarkers and enzyme-linked immunosorbent assay was performed to verify the results. The data identified haptoglobin (HPT) and α-1-microglobulin/bikunin precursor (AMBP) as two biomarkers with the highest ability to distinguish between healthy individuals and patients with nephropathy, and between diabetic patients with and without DN. Further, the HPT-to-creatinine ratio (HCR) was evaluated as an independent predictor of early renal functional decline (ERFD) in a cohort with an average follow-up of 4.2 years. The area under the curve (AUC) value for ERFD prediction was significantly improved when the HCR biomarker was included in the model with albumin to creatinine ratio (ACR) and baseline characteristics (AUC values were 0.803 and 0.759 for HCR and ACR, respectively; p value was 0.0423 for difference between models). In conclusion, our results suggest that HCR represents an early indicator of nephropathy, and a marker related to ERFD among diabetic patients in Taiwan.
Highlights
Diabetic nephropathy (DN) is a major complication of diabetes
Seven proteins (serotransferrin, ceruloplasmin, hemopexin, alpha-1-antitrypsin, beta-2-microglobulin, HPT, and α-1-microglobulin/bikunin precursor (AMBP)) were selected for further enzyme-linked immunosorbent assay (ELISA) validation as they were increased both in the WDM-NP group and the DM-NP group relative to healthy individuals and the DM-WNP group, respectively (Table 1)
A comparison of patients with albumin to creatinine ratio (ACR) of 30–300 mg/g and those with an ACR of < 30 mg/g yielded an Odds ratios (ORs) of 1.38 for developing early renal functional decline (ERFD), whereas a comparison of patients with a high and low HPT-to-creatinine ratio (HCR) yielded an OR of 4.47 after adjustment for follow-up time, systolic blood pressures (SBP), and estimated glomerular filtration rate (eGFR) levels
Summary
It is estimated that approximately 20–40% of type 2 diabetes (T2D) patients will develop renal disease [1,2]. DN is the leading cause of end-stage renal disease (ESRD) worldwide [3]. Analysis of the international statistics collected in the US Renal Data System indicates that Taiwan has the highest incidence and the second highest prevalence of ESRD worldwide [4,5]. The prognostic value of MA as a biomarker of disease progression is questionable, as patients with MA may exhibit the preservation of renal function [6]. Some studies indicate that a subset of diabetic patients with normal albuminuria may develop nephropathy [7], suggesting that patients may have declined renal function before the onset of MA. The identification of reliable biomarkers for the early prediction of DN and the development of effective treatment to reduce the incidence of ESRD is necessary
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