Urinary adiponectin in DKD

Aims: Since diabetes-associated kidney complication changes from diabetic nephropathy to diabetic kidney disease (DKD), more suitable biomarkers than urinary albumin are required. It has been hypothesized that urinary adiponectin (u-ADPN) is associated with the progression of DKD. We therefore evaluated the effectiveness of u-ADPN in predicting the decline of the renal function in patients with diabetes prior to end-stage renal disease. Methods: An ultrasensitive immune complex transfer enzyme immunoassay (ICT-EIA) was used to measure total and high molecular weight (HMW) adiponectin separately. We evaluated the relationships between the creatinine-adjusted urinary total-ADPN and HMW-ADPN, albumin (UACR) and liver-type fatty acid binding protein (L-FABP) at baseline and the 2-year change of the estimated glomerular filtration rate (ΔeGFR). Results: This 2-year prospective observational study included 201 patients with diabetes. These patients were divided into three groups according to their ΔeGFR: ≤-10 ml/min/1.73m2, >-10 and ≤0 ml/min/1.73m2, and >0 ml/min/1.73m2. Jonckheere-Terpstra test showed that lower ΔeGFR was associated with higher u-HMW-ADPN (p = 0.045). In logistic regression analysis, u-HMW-ADPN was associated with ΔeGFR after adjusted age, sex, and basal eGFR. Conclusion: Urinary HMW-ADPN could predict a declining renal function in patients with diabetes

Development of fully automated and ultrasensitive assays for urinary adiponectin and their application as novel biomarkers for diabetic kidney disease

Glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) are used to diagnose and classify the severity of chronic kidney disease. Total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) assays were developed using the fully automated immunoassay system, HI-1000 and their significance over conventional biomarkers were investigated. The T-AN and H-AN assays had high reproducibility, good linearity, and sufficient sensitivity to detect trace amounts of adiponectin in the urine. Urine samples after gel filtration were analyzed for the presence of different molecular isoforms. Low molecular weight (LMW) forms and monomers were the major components (93%) of adiponectin in the urine from a diabetic patient with normoalbuminuria. Urine from a microalbuminuria patient contained both high molecular weight (HMW) (11%) and middle molecular weight (MMW) (28%) adiponectin, although the LMW level was still high (52%). The amount of HMW (32%) and MMW (42%) were more abundant than that of LMW (24%) in a diabetic patient with macroalbuminuria. T-AN (r = − 0.43) and H-AN (r = − 0.38) levels showed higher correlation with estimated GFR (eGFR) than UAER (r = − 0.23). Urinary levels of both T-AN and H-AN negatively correlated with renal function in diabetic patients and they may serve as new biomarkers for diabetic kidney disease

Triggered Structural Control of Dynamic Covalent Aromatic Polyamides: Effects of Thermal Reorganization Behavior in Solution and Solid States

Thermally rearrangeable aromatic polyamides (TEMPO-PA) and random copolyamides (TEMPO-PA-COOH) incorporating alkoxyamine moieties in the main chain were synthesized, and the effects of thermal reorganization behavior on their solution and solid-state structures were investigated. The hydrodynamic radius in solution decreased as the solution temperature increased because of the dissociation of the alkoxyamine unit. Additionally, the dry density of the thin films decreased as the fabrication temperature increased because of the suppression of polymer aggregation caused by the thermally induced radical crossover reaction. In addition, at the film surface of the random copolyamide containing hydrophobic TEMPO and hydrophilic 3,5-diaminobenzoic acid (DABA) units, the hydrophilicity decreased as the fabrication temperature increased. This is because hydrophobic TEMPO and hydrophilic DABA units tend to be discretely aggregated near the film surface to minimize the surface energy and suppress the hydrogen bonding via a radical crossover reaction during the thin-film fabrication process. The present study clearly shows that both the solution structure and the solid-state molecular aggregation structure of the dynamic covalent polymers can be easily controlled by a thermal trigger, and it provides a new method for controlling the higher-order structure of polymer solutions and solids

Molecular composition of adiponectin in urine is a useful biomarker for detecting early stage of diabetic kidney disease

We previously developed two immune complex transfer enzyme immunoassays (ICT-EIA) to measure total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) in urine and have verified their usefulness as biomarkers for diabetic kidney disease. In this study, we developed T-AN and H-AN assays using the sandwich EIA (Sand-EIA). The reactivities of Sand-EIAs were compared with ICT-EIAs by measuring size exclusion chromatography (SEC) fractions of urine and adiponectin standard. As a result, ICT-EIAs showed higher macromolecular specificity. We then analyzed the molecular profile of adiponectin in the urine of 5 patients with different eGFR stages by measuring SEC fractions of urine. The results showed that smaller adiponectin correlated relatively well with eGFR stage. Finally, because SEC is time-consuming, we investigated that the ratio of T-ANs by Sand-EIA and ICT-EIA could be a good indicator of the monomer adiponectin. The ratio was evaluated using 77 urine samples from patients with diabetes and showed a significant decrease at an earlier stage compared with other biomarkers. In conclusion, we demonstrated a new index to estimate monomer adiponectin in urine by using Sand-EIA and ICT-EIA, and urinary monomer adiponectin can be a good early indicator of deterioration of renal function in diabetic patients