A study of high-, middle- and low-molecular weight adiponectin in urine as a surrogate marker for early diabetic nephropathy using ultrasensitive immune complex transfer enzyme immunoassay

2018 ◽  
Vol 55 (5) ◽  
pp. 525-534 ◽  
Author(s):  
Mayumi Yamamoto ◽  
Yuki Fujimoto ◽  
Shino Hayashi ◽  
Seiichi Hashida
Keyword(s):  
Molecular Weight ◽  
Diabetic Nephropathy ◽  
Enzyme Immunoassay ◽  
Immune Complex ◽  
Healthy Subjects ◽  
Surrogate Marker ◽  
Urinary Albumin ◽  
Low Molecular Weight ◽  
Patients With Diabetes ◽  
Estimate Glomerular Filtration Rate

Background For the early identification of patients at risk of developing diabetic nephropathy, we have developed an ultrasensitive immune complex transfer enzyme immunoassay to measure adiponectin in urine. Methods We developed immune complex transfer enzyme immunoassay for adiponectin and measured urinary adiponectin from 70 healthy subjects, 35 obese non-diabetic subjects and 20 patients with diabetes. Results The urinary adiponectin concentrations in patients with diabetes (3.3 ± 10.7 ng/mg creatinine) were significantly higher than those in obese subjects (0.54 ± 0.44; P < 0.01) and healthy subjects (0.46 ± 0.42; P < 0.001). The gel filtration elution profile of urine from healthy subjects showed traces of four immunoreactive peaks (high-, medium-, low-molecular weight and monomer molecules), despite the majority of blood adiponectin being high-molecular weight. However, urinary adiponectin molecules were more frequent in low-molecular weight as the estimate glomerular filtration rate decreased. Furthermore, as blood glucose concentrations rose, middle-molecular weight and high-molecular weight increased in urine. Further, urinary adiponectin concentrations correlated with estimate glomerular filtration rate ( r = −0.61, P < 0.001), but not urinary albumin. In addition, our analysis showed a significantly ( P < 0.001) higher value for urinary adiponectin in the G2 stage of chronic kidney disease classification where urinary albumin is not elevated. Conclusion Adiponectin increases in urine as renal function decreases, and urinary adiponectin may be useful as a surrogate marker for diabetic nephropathy risk.

scholarly journals ASSESSMENT OF NEPHRIN AND PODOCIN LEVELS IN THE URINE OF PATIENTS WITH DIABETES MELLITUS

2017 ◽  
Vol 21 (2) ◽  
pp. 33-40
Author(s):  
I. N. Bobkova ◽  
A. A. Shchukina ◽  
M. V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Serum Creatinine ◽  
Arterial Hypertension ◽  
Healthy Subjects ◽  
Early Diagnostics ◽  
Urinary Levels ◽  
Patients With Diabetes ◽  
Early Diabetic Nephropathy

THE AIM:to assess excretion value of podocytes injury biomarkers in urine and to clarify their significance for early diabetic nephropathy (DN) diagnostics in diabetes mellitus (DM) patients with different severity of albuminuria (AU)/proteinuria(PU).PATIENTS AND METHODS.74 DM pts were studied, including 30 with type1 DM (T1DM) and 44 pts with type2 DM (T2DM). They were divided into three groups: 41 pts with AU <30 mg/gCr (A1), 13 pts with AU 30-300 mg/gCr (A2), 20 pts with PU (A3). CKD S1 was revealed in 41pts, CKD S2 – in 25 pts, CKD S3 – in 8 pts. Arterial hypertension was observed in 52 pts of 74(70%), mainly in T2DM. 10 healthy subjects were studied as control. Urinary levels of nephrin and podocin (an important slit diaphragm proteins) were measured by ELISA.RESULTS.Nephrinuria (NU) >5,84ng/ml/g, which not detecting in controls, was revealed in 63% of A1 pts, in 77% – in A2, in 80% – in A3. Podocinuria (PdU)>1,73ng/ml/g was revealed in 78% of A1 pts, in 54% of A2 and in 83% – A3. NU in pts with PU was significantly higher than in AU<30 mg/g. PDU in groups with different AU/PU was equally high and has no differ between DM types. Direct correlation was obtained between NU and AU (R=0,947 p<0,05). NU and PdU in T1DM correlated directly with serum creatinine (R=0,489 p<0,05 and R=0,468 p<0,05) and indirectly with GFR (R=-0,461 p<0,05 and R=-0,36 р<0,05). In DM duration less than 5 years NU directly correlated with НbА1с level, in T2DM – indirectly with systolic blood pressure.CONCLUSON. Nephrin and podocin levels can be useful for early diagnostics and monitoring of DN. 

Pharmacokinetic of inhaled low molecular weight heparin

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7209-7209
Author(s):  
G. Scheuch ◽  
S. Haeussermann ◽  
P. Brand ◽  
C. Herpich ◽  
T. Meyer
Keyword(s):  
Molecular Weight ◽  
Anticancer Agents ◽  
Healthy Subjects ◽  
Area Under The Curve ◽  
Factor Xa ◽  
Inhalation Therapy ◽  
Attractive Alternative ◽  
Low Molecular Weight ◽  
Once Daily ◽  
Pharmacokinetic Behavior

7209 Background: Treatment with Heparin and low molecular weight (LMW) Heparin is frequently used in oncology settings. Usually, these drugs are delivered by subcutaneous (s.c.) administration. Since 1963, the clinical relevance of inhalation of unfractionated as well as LMW-Heparin has been investigated in various studies with over 500 subjects. In this study, a single inhalation of the LMW-Heparin Certoparin (Mono-Embolex, Novartis) was investigated in 10 healthy subjects. The goal was to assess the pharmacokinetic behavior. Inhalations were performed using a novel inhalation system, which allows an accurate dosing in the lungs by controlling patient’s breathing pattern (AKITA). Lung deposition is about 85% of the emitted dose. Methods: 10 non-smoking healthy subjects participated in this study. Inhalation of 9000 IU of LMW-Heparin was compared to 3000 IU s.c. administration to achieve factor-Xa-activity in the plasma of 0.2 to 0.3 U/ml. Intravenous blood samples were taken 0.25, 0.5, 1, 2, 4, 6, 24, 48 hrs after administration. Factor-Xa-activity in plasma was assessed using the Berichrom assay (Dade Behring, Marburg, Germany). Results: Inhalation of LMW-Heparin was well tolerated and did not result in any side effects or changes in lung function. The maximum anti-Xa-activity in the plasma was 0.3 U/ml for the s.c. administration of Certoparin and 0.32 U/ml after inhalation of 9000 IU. However, pharmacokinetics was considerably different. Inhaled LMW-Heparin resulted in a prolonged anti-Xa-activity. After 6 (24) hours, the anti-Xa-activity after s.c. administration was down at 0.16 U/ml (0.10) and after inhalation at 0.30 (0.18) U/ml. Even after 48 hrs, the anti-Xa-activity after inhalation was significantly higher than the baseline value. Comparing area under the curve (AUC), bioavailability for the inhalation was 9.4 U · h/ml ± 14% compared to 5.7 U · h/ml ± 27% after s.c. administration. Conclusions: These results suggest that with controlled inhalation, this administration route is an attractive alternative to s.c. administration, with the result of longer bioavailability and less variability. A once daily administration is possible. Inhalation therapy with these kind of systems might also be useful with different anticancer agents, which cannot be administered orally. [Table: see text]

Association of serum pentraxin 3 concentrations with diabetic nephropathy

2016 ◽  
Vol 64 (6) ◽  
pp. 1124-1127 ◽  
Author(s):  
Rui Wang ◽  
Jietao Zhang ◽  
Wenchao Hu
Keyword(s):  
Diabetic Nephropathy ◽  
Healthy Subjects ◽  
Renal Damage ◽  
Urinary Albumin Excretion ◽  
Urinary Albumin ◽  
Pentraxin 3 ◽  
Elisa Kit ◽  
Simple Regression Analysis ◽  
Simple Regression

Pentraxin 3 (PTX3), a member of a superfamily of conserved proteins, attenuates renal damage in diabetic mice. This study aims to determine whether serum PTX3 concentrations are correlated with the presence of diabetic nephropathy (DN). A total of 160 patients with type 2 diabetes mellitus (T2DM) and 54 healthy subjects were enrolled in this study. Patients with T2DM were divided into three groups in accordance with the levels of urinary albumin excretion (UAE). Serum PTX3 concentrations were determined using an ELISA kit. Serum PTX3 concentrations were significantly higher in patients with T2DM compared with the controls. Patients with T2DM with macroalbuminuria showed higher serum PTX3 concentrations compared with the other three groups. However, there were no significant differences of serum PTX3 concentrations between patients with T2DM with normoalbuminuria and microalbuminuria. Furthermore, a simple regression analysis has shown that serum PTX3 concentrations in patients with T2DM were negatively correlated with body mass index, and positively correlated with blood urea nitrogen, serum creatinine, and UAE. Serum PTX3 concentrations are correlated with DN.

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